Insomnia in the elderly: treatment with flurazepam hydrochloride.
Under sleep-laboratory control, the efficacy of flurazepam hydrochloride (15 mg) was evaluated in 6 women (age range, 67-82 years) with objectively verified insomnia. A 15-night, single-blind, crossover procedure was followed. Sleep records obtained during 3 placebo-baseline nights, 7 consecutive flurazepam nights, and 3 placebo-withdrawal nights were evaluated by means of electroencephalographic, electro-oculographic, and electromyographic criteria. A statistically significant reduction in sleep latency and total awake time and a corresponding increase in total sleep time (P less than 0.05) were demonstrated during the active drug period. No evidence of diminishing effectiveness was observed during the 7 days of drug administration. For the rapid-eye-movement (REM) stage, a significant decrease (P less than 0.05) in mean REM percent was noted during the drug period despite an increase in mean absolute REM time. No REM rebound occurred upon drug withdrawal. There were no significant changes in mean percentages for stages 3 and 4 during the drug period and the withdrawal period. Adverse reactions were rare (chiefly some daytime drowsiness in 2 subjects).


Primary spinal glioblastoma treated with adjuvant radiation and temozolomide: Report of two cases.
Primary spinal glioblastoma multiforme (GBM) is a rare entity, which is invariably associated with poor outcome. Standard treatment is surgery followed by post-operative radiotherapy. Due to paucity of cases role of chemotherapy is investigational. We intend to report two cases of primary spinal GBM treated with radiation and adjuvant temozolomide.


This paper describes an attempt to find a difference between the patterns of methylation of E. coli tRNA by extracts of two mouse tissues. Two samples of tRNAs, methylated in two separate experiments with extracts of myeloma and of liver in presence of either 14C or 3H S-Adenosyl-L-Methionine, were pooled and fractionated together on a RPC column. The results show a difference in the specificities of the two extracts. Chromatography on DEAE Sephadex suggests that the tRNA Met is methylated by the enzymes on the myeloma, while enzymes from liver react very little, if at all, with that particular tRNA species. Studies have been undertaken in order to find out whether similar differences can also be demonstrated in homologous systems.


Bioequivalency of oral suspension formulations of cefixime.
A study was performed in 24 healthy male subjects to establish that two suspension formulations of cefixime were bioequivalent to each other and to a reference oral solution. A single 400 mg oral dose of the drug was given in a randomized three-way crossover design as two suspensions (a research suspension (RS) used during clinical trials and a suspension intended for marketing (MS] and a reference oral solution (SOL). Each dose was separated from the other by a 3-day washout period. Mean peak serum concentrations (Cmax) were 4.67, 4.10, and 4.27 micrograms ml-1 after the MS, RS, and SOL, respectively. Although comparison (ANOVA) of the mean pharmacokinetic parameters for cefixime found significant differences (p less than 0.05) in Cmax, the time to Cmax, and area under the serum concentration time curve (AUC 0----infinity) values among the three formulations, the mean differences were less than 20 per cent. No significant differences (p greater than 0.05) were found in either the elimination half-life or renal clearance of unchanged drug. Overall, with a 98 per cent power to detect a 20 per cent difference in AUC0----infinity or urinary recovery values between the formulations tested, the results show that the MS was bioequivalent to the RS and that both suspensions were bioequivalent to the SOL.


Effects of modulated RF energy on the EEG of mammalian brains. Effects of acute and chronic irradiations.
The effects of modulated radio frequency fields on mammalian EEGs were investigated using acute and chronic irradiations at non-thermal level. The EEG signals were computer processed to obtain power spectra. Rabbits were exposed to the field for 2 h a day for 6 weeks at 1-10 MHz (15 Hz modulation) at the level of 0.5-1 kV/M. Silver electrodes placed on the skull surface were used for recording of the EEG. Usually they were removed immediately after initial recordings of the EEG and reinserted before the final and intermediate EEG recordings. With this arrangement, modulated RF fields produced a change in EEG patterns by enhancing the low frequency components and decreasing high frequency activities. On the other hand, acute irradiations did not produce noticeable changes in the EEG at the level of 0.5-1 kV/M (1-30 MHz, 60 Hz modulation) as long as the use of intracranial electrodes was avoided.


Structural identification, subcellular localization and secretion of bovine adrenomedullary neuromedin C [GRP-(18-27)].
Bombesin-like immunoreactivity (BLI) was purified from acid (HCl) extracts of bovine adrenal medulla. High performance liquid chromatography (HPLC) on a mu-Bondapak C18 column revealed the presence of five molecular forms of BLI, one coeluting with synthetic gastrin releasing peptide (GRP), the mammalian counterpart of amphibian bombesin, one coeluting with neuromedin C, one coeluting with neuromedin B and the two other ones coeluting with the oxidized forms of neuromedins B and C. The material corresponding to neuromedin C was purified to homogeneity and its amino acid composition and sequence corresponded to those expected for neuromedin C. HPLC analysis on an analytical SP-5PW column of subcellular extracts of bovine adrenal medulla indicated that neuromedin C is almost exclusively localized in secretory granules. The neuropeptide function of neuromedin C and/or other BLI peptides at this level was supported by the stimulatory effect of carbamylcholine (500 microM) on the release of BLI (4.5-fold increase over the basal release of 19 fmol/5 min) from perfused bovine adrenal glands.


Ir gene control of immune responses to insulins. II. Phenotypic differences in T cell activity among nonresponder strains of mice.
Immune responses by mice to heterologous insulins are controlled by H-2 linked Ir genes. In studies to determine the mechanisms responsible for nonresponsiveness, we found that although pork insulin failed to stimulate antibody or proliferative responses in H-2b mice, it did prime T cells that can express helper activity in adoptive recipient mice. This helper activity was insulin-specific in both elicitation and expression. In studies presented in this paper, we have extended this analysis to the response patterns of helper T cells stimulated by sheep, horse, and rat insulins in mice bearing different H-2 haplotypes. The results demonstrate that nonresponder forms of insulin, including rat insulin, prime T cells in H-2b and H-2d, but not H-2k, mice. These results suggest that regulation of nonresponsiveness to insulin appears to be through different pathways in mice bearing different H-2 haplotypes.


Activation of parabrachial nucleus - ventral tegmental area pathway underlies the comorbid depression in chronic neuropathic pain in mice.
Depression symptoms are often found in patients suffering from chronic pain, a phenomenon that is yet to be understood mechanistically. Here, we systematically investigate the cellular mechanisms and circuits underlying the chronic-pain-induced depression behavior. We show that the development of chronic pain is accompanied by depressive-like behaviors in a mouse model of trigeminal neuralgia. In parallel, we observe increased activity of the dopaminergic (DA) neuron in the midbrain ventral tegmental area (VTA), and inhibition of this elevated VTA DA neuron activity reverses the behavioral manifestations of depression. Further studies establish a pathway of glutamatergic projections from the spinal trigeminal subnucleus caudalis (Sp5C) to the lateral parabrachial nucleus (LPBN) and then to the VTA. These glutamatergic projections form a direct circuit that controls the development of the depression-like behavior under the state of the chronic neuropathic pain.


Using single nucleotide polymorphism array for prenatal diagnosis in a large multicenter study in Southern China.
Numerous studies have evaluated the use of single nucleotide polymorphism array (SNP-array) in prenatal diagnostics, but very few have evaluated its application under different risk conditions. Here, SNP-array was used for the retrospective analysis of 8386 pregnancies and the cases were categorized into seven groups. Pathogenic copy number variations (pCNVs) were found in 699 (8.3%, 699/8386) cases. Among the seven different risk factor groups, the non-invasive prenatal testing-positive group had the highest pCNVs rate (35.3%), followed by the abnormal ultrasound structure group (12.8%), and then the chromosomal abnormalities in the couples group (9.5%). Notably the adverse pregnancy history group presented with the lowest pCNVs rate (2.8%). Further evaluation of the 1495 cases with ultrasound abnormalities revealed that the highest pCNV rates were recorded in those cases with multiple system structure abnormalities (22.6%), followed by the groups with skeletal system (11.6%) and urinary system abnormalities (11.2%). A total of 3424 fetuses with ultrasonic soft markers were classified as having one, two, or three ultrasonic soft markers. The different pCNV rates in the three groups were statistically significant. There was little correlation between pCNVs and a previous history of adverse pregnancy outcomes, suggesting that genetic screening under these conditions should be evaluated on a case-by-case basis.


Reconstruction of ancient genome and gene order from complete microbial genome sequences.
Microbial genome sequences provide us with the fossil records for inferring their origination and evolution. Assuming that current microbial genomes are the evolutionary results of ancient genomes or fragments and the neighboring genes in ancient genomes are more likely neighbors in current genomes, in this paper we proposed a paleontological algorithm and assembled the orthologous gene groups from 66 complete and current microbial genome sequences into a pseudo-ancient genome, which consists of continuous fragments of various sizes. We performed bootstrap resampling and correlation analyses and the results showed that the assembled ancient genome and fragments are statistically significant and the genes of the same fragment are inherently related and likely derived from common ancestors. This method provides a new computational tool for studying microbial genome structure and evolution.


Immunoblot identification of phosphorylated basic proteins of rat and rabbit CNS and PNS myelin: evidence for four phosphorylated basic proteins and P2 in rat PNS myelin.
The immunoblot technique permits the visualization of proteins following their separation on acrylamide gels, transfer to cellulose nitrate sheets and subsequent staining with antiserum. We have utilized this technique to demonstrate the presence of four basic proteins in rat PNS myelin with molecular weights of 21K, 18K, 17K, and 14K. Similarly, we demonstrated the presence of two basic proteins in rabbit PNS myelin (molecular weights of 21K and 18K). Exposure of the immunostained cellulose nitrate strips to X-ray film revealed the phosphorylation of four and two basic proteins in rat and rabbit PNS myelin, respectively. These basic proteins were present in the CNS myelin of the two species and were also phosphorylated. Because of the sensitivity of the immunoblot technique, it was also possible for us to visualize the P2 protein in both rat and rabbit PNS myelin.


Muscarinic acetylcholine neurotransmission enhances the late-phase of long-term potentiation in the hippocampal-prefrontal cortex pathway of rats in vivo: a possible involvement of monoaminergic systems.
The prefrontal cortex is continuously required for working memory processing during wakefulness, but is particularly hypoactivated during sleep and in psychiatric disorders such as schizophrenia. Ammon's horn CA1 hippocampus subfield (CA1) afferents provide a functional modulatory path that is subjected to synaptic plasticity and a prominent monoaminergic influence. However, little is known about the muscarinic cholinergic effects on prefrontal synapses. Here, we investigated the effects of the muscarinic agonist, pilocarpine (PILO), on the induction and maintenance of CA1-medial prefrontal cortex (mPFC) long-term potentiation (LTP) as well as on brain monoamine levels. Field evoked responses were recorded in urethane-anesthetized rats during baseline (50 min) and after LTP (130 min), and compared with controls. LTP was induced 20 min after PILO administration (15 mg/kg, i.p.) or vehicle (NaCl 0.15 M, i.p.). In a separate group of animals, the hippocampus and mPFC were microdissected 20 min after PILO injection and used to quantify monoamine levels. Our results show that PILO potentiates the late-phase of mPFC LTP without affecting either post-tetanic potentiation or early LTP (20 min). This effect was correlated with a significant decrease in relative delta (1-4 Hz) power and an increase in sigma (10-15 Hz) and gamma (25-40 Hz) powers in CA1. Monoamine levels were specifically altered in the mPFC. We observed a decrease in dopamine, 5-HT, 5-hydroxyindolacetic acid and noradrenaline levels, with no changes in 3,4-hydroxyphenylacetic acid levels. Our data, therefore, suggest that muscarinic activation exerts a boosting effect on mPFC synaptic plasticity and possibly on mPFC-dependent memories, associated to monoaminergic changes.


Evaluation of functional degeneration of the amazon-ant Polyergus rufescens Latr. under an influence of socially parasitic way of life.
In certain, infrequently occurring, favorable circumstances the ants P. rufescens can display patterns of behavior which seem to be disappearing as a result of their parasitic way of life: the ability to food themselves, independently though ineffectively, elements of the offspring-protection behavior, transporting of nestmates, escape reaction. Similar events reinforce the infrequently used, latent reflexes, preventing their complete extinction. It is supposed that the characteristic in conventional parasitism disappearance of certain elements of behavior is inhibited by a social way of life. It may also be true of other, non-insect communities.


Chromosomal markers in the genus Karenia: Towards an understanding of the evolution of the chromosomes, life cycle patterns and phylogenetic relationships in dinoflagellates.
Dinoflagellates are a group of protists whose genome is unique among eukaryotes in terms of base composition, chromosomal structure and gene expression. Even after decades of research, the structure and behavior of their amazing chromosomes-which without nucleosomes exist in a liquid crystalline state-are still poorly understood. We used flow cytometry and fluorescence in situ hybridization (FISH) to analyze the genome size of three species of the toxic dinoflagellate genus Karenia as well the organization and behavior of the chromosomes in different cell-cycle stages. FISH was also used to study the distribution patterns of ribosomal DNA (45S rDNA), telomeric and microsatellites repeats in order to develop chromosomal markers. The results revealed several novel and important features regarding dinoflagellate chromosomes during mitosis, including their telocentric behavior and radial arrangement along the nuclear envelope. Additionally, using the (AG)10 probe we identified an unusual chromosome in K. selliformis and especially in K. mikimotoi that is characterized by AG repeats along its entire length. This feature was employed to easily differentiate morphologically indistinguishable life-cycle stages. The evolutionary relationship between Karenia species is discussed with respect to differences in both DNA content and the chromosomal distribution patterns of the DNA sequences analyzed.


Cell-specific detection of jasmonates by means of an immunocytological approach.
To determine the location of specific molecules within tissues or cells, immunological techniques are frequently used. However, immunolocalization of small molecules, such as jasmonic acid (JA) and its bioactive amino acid conjugate, JA-isoleucine, requires proper fixation and embedding methods as well as specific antibodies. In this chapter, we present a method to prepare plant tissues for the detection of jasmonates, including the chemical fixation to immobilize JA within the tissue, the subsequent embedding in a suitable medium, and the immunolabeling procedure itself.


Cognitive Enhancement Using ICT and Its Ethical Implications.
The utilization of digital tools aiming at the cognitive enhancement of students and adults, so that they can achieve better performance and professional or academic success, has increased in recent years. This paper focuses on ICT tools such as computer games, programming languages and educational software as means for cognitive enhancement and attempts to highlight their contributions. Issues of design and the limitations of digital tools are discussed. In the final section, the ethical implications of using educational ICT tools for cognitive enhancement from a virtue ethics perspective are presented.


Transfer learning with deep convolutional neural network for automated detection of schizophrenia from EEG signals.
Schizophrenia (SZ) is a severe disorder of the human brain which disturbs behavioral characteristics such as interruption in thinking, memory, perception, speech and other living activities. If the patient suffering from SZ is not diagnosed and treated in the early stages, damage to human behavioral abilities in its later stages could become more severe. Therefore, early discovery of SZ may help to cure or limit the effects. Electroencephalogram (EEG) is prominently used to study brain diseases such as SZ due to having high temporal resolution information, and being a noninvasive and inexpensive method. This paper introduces an automatic methodology based on transfer learning with deep convolutional neural networks (CNNs) for the diagnosis of SZ patients from healthy controls. First, EEG signals are converted into images by applying a time-frequency approach called continuous wavelet transform (CWT) method. Then, the images of EEG signals are applied to the four popular pre-trained CNNs: AlexNet, ResNet-18, VGG-19 and Inception-v3. The output of convolutional and pooling layers of these models are used as deep features and are fed into the support vector machine (SVM) classifier. We have tuned the parameters of SVM to classify SZ patients and healthy subjects. The efficiency of the proposed method is evaluated on EEG signals from 14 healthy subjects and 14 SZ patients. The experiments showed that the combination of frontal, central, parietal, and occipital regions applied to the ResNet-18-SVM achieved best results with accuracy, sensitivity and specificity of 98.60% ± 2.29, 99.65% ± 2.35 and 96.92% ± 2.25, respectively. Therefore, the proposed method as a diagnostic tool can help clinicians in detection of the SZ patients for early diagnosis and treatment.


Assessment of forest fire emissions in Uttarakhand State, India, using Open Geospatial data and Google Earth Engine.
In the recent past, forest fires have increased due to the changing climate pattern. It is necessary to analyse and quantify various gaseous emissions so as to mitigate their harmful effects on air pollution. Satellite remote sensing data provides an opportunity to study the greenhouse gases in the atmosphere. The multispectral sensor of the Tropospheric Monitoring Instrument (Sentinel-5) is capable of recording the reflectance of wavelengths vital for measuring the atmospheric concentrations of methane, formaldehyde, aerosol, carbon monoxide, etc., at a spatial resolution of 0.01°. The present study utilized the Google Earth Engine (GEE) platform to study the emissions caused by forest fires in four districts of Uttarakhand State of India, which witnessed unprecedented fires in April-May 2021. All the datasets were ingested in GEE, which has the capability to analyse large datasets without the need to download them. The pre-fire period chosen was September 2020; the fire period was February-May 2021, and the post-fire period was June 2021. The variables chosen were aerosol absorbing index (AAI), carbon monoxide (CO) and nitrogen dioxide (NO2). The climate parameter temperature (Moderate Resolution Imaging Spectroradiometer Land Surface Temperature) and precipitation (from Climate Hazards Group InfraRed Precipitation (CHIRPS) Pentad) were also studied for the period mentioned. The results indicate a different trend for emissions in each district. For AAI, maximum emissions were noted in district Nainital followed by Almora, Tehri Garhwal and Garhwal. For CO emissions, the most affected district was Almora followed by Nainital, Garhwal and Tehri Garhwal. For NO2 emissions, the most affected district was Garhwal, followed by Nainital, Tehri Garhwal and Almora. Delta Normalized Burn Ratio was computed from Sentinel data (difference of pre-fire and post-fire images) to assess the burnt area severity. The Delta Normalized Burn Ratio values observed that the district with the most burnt area is Garhwal, followed by Nainital, Almora and Tehri Garhwal. The elevated temperatures and scanty rainfall patterns regulated the intensity and duration of forest fire. Monitoring the gaseous emissions as a consequence of forest fire in the GEE platform is much easier and more convenient at a regional level. Such data is much needed for mitigation measures to be implemented in time.


Oxidation of Arg-410 promotes the elimination of human serum albumin.
The effect of the oxidation of amino acid residues on albumin on its in vivo elimination was investigated using mutants and oxidized HSAs. The single-residue mutants (H146A, K199A, W214A, R218H, R410A, Y411A) and oxidized HSAs were produced by the recombinant DNA techniques and incubation with a metal ion-catalyzed oxidation (MCO) system for 12, 24, 48 or 72 h. Pharmacokinetics were evaluated in mice after labeling with 111In. Structural and functional properties were examined by several spectroscopic techniques. Time-dependent increase in carbonyl group content resulted in increase in the liver clearance of oxidized HSAs. Slight decreases in alpha-helical content as the result of oxidation was induced by the increases in accessible hydrophobic areas and the net negative charge on the HSA molecule. No significant change in the pharmacokinetics and structural properties was observed for the W214A, R218H and Y411A mutants, but the properties for the H146A, K199A and R410A mutants were affected (extent of effect: R410A > K199A > H146A). The liver clearance of these proteins is closely correlated to hydrophobicity (r = 0.929, P < 0.01) and the net charge of the proteins (r=0.930, P < 0.01). The rate of elimination of HSA is closely related to the hydrophobicity and net charge of the molecule. Further, the R410A mutants had a short half-life and structure similar to oxidized HSA after oxidation. Therefore, the modification of Arg-410 via oxidative stress may promote the elimination of HSA.


High glutamate concentration reverses the inhibitory effect of microglial adenosine 2A receptor on NLRP3 inflammasome assembly and activation.
NLRP3 inflammasome plays a crucial role in the innate immune system. Our group previously reported that the microglial adenosine 2A receptor (A2AR) regulates canonical neuroinflammation, which is affected by the glutamate concentration. However, the regulatory effect of A2AR on NLRP3 inflammasome and the effects of glutamate concentration remain unknown. Therefore, we aimed to investigate the regulatory effect of microglial A2AR on NLRP3 inflammasome assembly and activation as well as the effects of glutamate concentration on the inflammasome assembly and activation. Experiments were conducted on magnetically sorted primary microglia from P14 mice. The results showed that pharmacological A2AR activation ameliorated NLRP3 activation under no or low glutamate concentrations, but this effect was reversed by high glutamate concentrations. Moreover, the mRNA levels of NLRP3 inflammasome-related genes were not affected by A2AR activation or the glutamate concentration. We further demonstrated that A2AR activation inhibited the interaction between NLRP3 and caspase 1 under no or low glutamate concentrations while promoting their interaction under high glutamate concentrations. The oligomerization of ASC also showed a similar trend. In conclusion, our findings proved that the high glutamate concentration could reverse the inhibition of A2AR on NLRP3 inflammasome activation by modulating its assembly, which provides new insights into the regulatory effect of A2AR on neuroinflammation under different pathological conditions.


The tryphosine genus Cheirimedon in Australian waters (Crustacea, Amphipoda, Lysianassidae, Tryphosinae).
The genus Cheirimedon is reviewed and the monotypic genus Tryphosoides placed in its synonymy. We describe fourteen new species of Cheirimedon, all from Australian waters, bringing the total number of species in the genus to 22. Full synonymies and distribution data are provided for all taxa. A key to the world species is provided.


Nitric oxide as a peripheral and central mediator in temperature regulation.
In animals including humans nitric oxide (NO) serves as a biological messenger both peripherally at neuroeffector junctions and in the central nervous system where it modulates neuronal activity. Evidence for the involvement of NO in homeostatic control is accumulating also for temperature regulation in homeotherms. In the periphery an auxiliary role in the vasomotor control of convective heat transfer to heat dissipating surfaces and modulation of thermoregulatory heat generation, especially in brown adipose tissue as the site of nonshivering thermogenesis, are discussed as NO actions. At the central level a thermolytic role of NO in thermoregulation as well as in fever is assumed, however, experimental data opposing this view suggest that topical specificity may be important. At the level of single neurons, the observed interrelationships between thermosensitivity and responsiveness to NO are still not consistent enough to reconcile these data with the effects of NO-donors and inhibitors of NO-synthase on temperature regulation.


Relationships between characteristics of electrical stimulation, muscle pain and blink responses in man.
The present research was undertaken in 11 healthy volunteers with the aim of investigating the relationship between blink response, a feature of the startle reaction, and muscular pain evoked by muscle electrical stimulation (train of stimuli). At a repetition rate of 0.1 Hz, a close relationship was found between the threshold for muscle pain and that for the blink response, without apparent habituation. At the same rate and with stimulation intensity maintained at pain threshold, the subject could voluntarily inhibit the blink response, but not pain. Under the same conditions both pain and blink response were inhibited during a mental task. By increasing the current intensity pain became more intense and the blink response tended to increase in amplitude and to decrease in latency. Similar effects were achieved by increasing the repetition rate with the current intensity maintained at pain threshold. Habituation of the blink response, but not of pain, was found at repetition rates of 1 Hz or more. Present results indicate that nociceptive inputs from muscle have a facilitatory effect on central mechanisms subserving the blink response. It is suggested that the comparative analysis of pain sensation and the blink response may be a useful tool for pain research in man.


Rapid and micro high-pressure liquid chromatographic method for simultaneous determination of procainamide and N-acetylprocainamide in plasma.
A rapid and simple high-pressure liquid chromatographic method was developed for the simultaneous determination of plasma levels of procainamide and its major metabolite, N-acetonitrile, and the supernate was chromatographed on a cation-exchange column. The assay can be carried out on as little as 20 microliter of plasma and requires only about 7 min for each sample. No interference was found in plasma samples from cardiac patients receiving procainamide. This method is simple, fast, and useful for routine therapeutic monitoring and for pharmacokinetic studies procainamide and its metabolite.


Parents as change agents in the management of their developmentally delayed children's noncompliant behaviors: a critical review.
The present paper reviews the behavioral parent training literature that has focused on reducing noncompliance with developmentally delayed children. Several factors are identified which may make parental attempts to reduce developmentally delayed children's noncompliance difficult. The 13 studies reviewed are separated into group and single case approaches, and each study was assessed on a number of methodological factors. The studies generally report success in modifying non-compliance; however, the variability in the experimental rigor of the reviewed studies preclude definitive conclusions from being made at this time about the efficacy of training parents to reduce noncompliance with delayed children. As examples, only a few studies have collected parental data and home observational data. Clinical and training considerations are also discussed, such as the need to identify parental and marital characteristics that may influence training success and identify which specific training techniques are most effective in teaching parents contingency management procedures. Finally, suggestions for training parents of delayed children are offered.


A systematic review of clinical studies on variable proton Relative Biological Effectiveness (RBE).
Recently, a number of clinical studies have explored links between possible Relative Biological Effectiveness (RBE) elevations and patient toxicities and/or image changes following proton therapy. Our objective was to perform a systematic review of such studies. We applied a "Problem [RBE], Intervention [Protons], Population [Patients], Outcome [Side effect]" search strategy to the PubMed database. From our search, we retrieved studies which: (a) performed novel voxel-wise analyses of patient effects versus physical dose and LET (n = 13), and (b) compared image changes between proton and photon cohorts with regard to proton RBE (n = 9). For each retrieved study, we extracted data regarding: primary tumour type; size of patient cohort; type of image change studied; image-registration method (deformable or rigid); LET calculation method, and statistical methodology. We compared and contrasted their methods in order to discuss the weight of clinical evidence for variable proton RBE. We concluded that clinical evidence for variable proton RBE remains statistically weak at present. Our principal recommendation is that proton centres and clinical trial teams collaborate to standardize follow-up protocols and statistical analysis methods, so that larger patient cohorts can ultimately be considered for RBE analyses.


3D and cinematic rendering of abdominopelvic pathology in the peripartum period.
3D with volume rendering and the more recently described technique of cinematic rendering are post-processing techniques that create reconstructions of cross sectional imaging data which enhance image interpretation. This review illustrates the potential applications of volume rendering, 3D, and cinematic rendering in the evaluation of abdominopelvic pathology in the peripartum period. These techniques show promise in improving visualization of pelvic structures, vascular mapping, highlighting textural differences between tissues, and improving understanding of spatial relationships.


Ultrasonography and Sonoelastography Characteristics of Benign vs. Malignant Mesenteric Lymph Nodes in Cats: An Update.
(1) Background: Strain elastography (SE) is an ultrasound-based technique able to non-invasively assess tissue elasticity, with malignant tissues being stiffer than normal tissues. The purpose of the study was to evaluate the diagnostic performance of SE to differentiate feline mesenteric benign and malignant lymph nodes (LNs) using a multivariate approach including both SE results and B-mode ultrasound and color Doppler findings. (2) Methods: Feline enlarged mesenteric LNs were evaluated using B-mode ultrasound, color Doppler ultrasonography, and SE. Short-to-long axis ratios, borders, echogenicity, hilum, vascular flow distribution, elastographic patterns, and strain ratios were recorded. Histological and/or cytological diagnosis was available for each LN. (3) Results: A total of 88 LNs were included, 46 (52.3%) benign and 42 (47.7%) malignant; in the benign group, 40 LNs had a diagnosis of reactive hyperplasia (group A) and 6 eosinophilic sclerosing lymphadenitis (group B), while in the malignant group 42 had a diagnosis of lymphoma (group C). The principal component analysis approach showed evidence that by combining B-mode- and color Doppler-based scores with SE scores, the three groups of LNs can be accurately distinguished. (4) Conclusions: Our results demonstrate that a multivariate sonographic approach combining B-mode ultrasound, color Doppler ultrasonography, and SE can accurately distinguish benign from malignant LNs, thus helping in the clinical advice of feline patients.


Differential perceptions of body image and body weight among adults of different socioeconomic status in a sub-urban population.
This study explored the association of socioeconomic status with individuals' perception of their body image (BI) and body weight (BW) among adults in a sub-urban Nigerian population. The cross-sectional sample comprised 1521 residents (775 males and 746 females) of the town of Nnewi. Perceived BI was assessed using figural representations of different sizes for males and females. Perceived BW was determined by presenting participants with BW category options to choose from. Body mass index (BMI) was calculated from objectively measured BW and height using standardized procedures. Actual BW categories were derived from participants' BMIs using WHO criteria. Perceived BI and BW differed from actual BW among unskilled and non-tertiary males (p<0.001) and female (p<0.001 to p<0.04) in all BW categories whereas these variables differed (p<0.001) among skilled and tertiary males and females in normal weight, overweight and obese categories. Perceived BW differed (p<0.001) from actual BW among unskilled and non-tertiary males in underweight, overweight and obese categories whereas these variables differed (p<0.001) among unskilled and non-tertiary females, skilled and tertiary males and females in overweight and obese categories. Underweight 'unskilled' and 'non-tertiary' males perceived their BI to be different from their actual BW (p<0.001). Overweight and obese 'skilled' and 'unskilled', and 'tertiary' and 'non-tertiary', males and females perceived their BI and BW to be different from their actual BW (p<0.001). Significant differences in perceived BI existed between 'skilled' and 'unskilled' (p<0.001), and 'tertiary' and 'non-tertiary' (p=0.005), overweight males, and between 'skilled' and 'unskilled' (p<0.001), and 'tertiary' and 'non-tertiary' (p=0.008), normal-weight females. The 'skilled' participants had a lower risk of perceiving a larger BI (OR 0.51, 95% CI 0.41-0.64; p<0.001) and larger BW (OR 0.71, 95% CI 0.53-0.96; p=0.03) than the 'unskilled' participants. The 'tertiary' participants had a lower risk of perceiving a larger BI (OR 0.51, 95% CI 0.40-0.63; p<0.001) and larger BW (OR 0.71, 95% CI 0.53-0.95; p=0.02) than the 'non-tertiary' participants. After adjusting for possible confounders, all the risks became insignificant except for perception of BI by the 'skilled' participants (OR 0.70, 95% CI 0.50-0.99; p=0.04). Individuals in the different occupational and educational categories perceived their BI differently but their BW similarly. Given the same BMI, age, perceived ideal BI and sex, only occupation is found to be associated with perception of BI.


A dual function for the chromatin organizer Special A-T rich Binding Protein 1 in B-lineage cells.
SATB1 (Special A-T rich Binding protein 1) is a cell type-specific factor that regulates the genetic network in developing T cells and neurons. In T cells, SATB1 is required for lineage commitment, VDJ recombination, development and maturation. Considering that its expression varies during B-cell differentiation, the involvement of SATB1 needs to be clarified in this lineage. Using a KO mouse model in which SATB1 was deleted from the pro-B-cell stage, we examined the consequences of SATB1 deletion in naive and activated B-cell subsets. Our model indicates first, unlike its essential function in T cells, that SATB1 is dispensable for B-cell development and the establishment of a broad IgH repertoire. Second, we show that SATB1 exhibits an ambivalent function in mature B cells, acting sequentially as a positive and negative regulator of Ig gene transcription in naive and activated cells, respectively. Third, our study indicates that the negative regulatory function of SATB1 in B cells extends to the germinal center response, in which this factor limits somatic hypermutation of Ig genes.


Fear of Recurrence in Young Adult Cancer Patients-A Network Analysis.
Due to the high survival rates of many young cancer patients and a high risk of second tumors, fear of cancer recurrence (FCR) can cause serious impairment for adolescent and young adult (AYA) cancer patients. The aim of this study is to analyze the structure of the Fear of Disease Progression Questionnaire (FoP-Q-12) to better understand the construct of FCR. We performed a cross-sectional survey on a sample of AYA patients aged 15-39 years with different tumor entities. FCR was measured using the FoP-Q-12, and a network analysis was conducted to examine the relationship of FCR symptoms. The importance of individual items in the network was determined using centrality analyses. A total of 247 AYA patients (81.8% female, median age 31.0 years) participated in the study. The mean FCR score in the sample was 35.9 (SD = 9.9). The majority of patients reported having high FCR (59.5%), according to the established cut-off. The two questionnaire items with the strongest association related to fears about work, and the most central symptom was the fear of serious medical interventions. The centrality of emotional issues in the sample indicates that these symptoms should be prioritized in the development of interventions targeting FCR. Further research should address this topic with larger samples of patients in other age groups and in longitudinal studies.


Factors that predict incomplete colonoscopy.
Certain factors in a patient's history, such as prior abdominal surgery or complicated diverticular disease, have been reported to hinder cecal intubation during colonoscopy. Over a 16-month period, 1,047 consecutive colonoscopies were prospectively evaluated to determine whether these factors were indeed clinically relevant. Of the 90 patients (9 percent) who had incomplete intubation of the colon, there were significantly more women (66 percent) than men (34 percent) (P < 0.001). Women with a history of abdominal hysterectomy had a significantly lower cecal intubation rate (P < 0.01). A history of diverticulitis did not alter the cecal intubation rate. In patients with incomplete colonic intubation, the most proximal extent of intubation was the sigmoid colon in women (31 percent) and the right colon in men (68 percent). Sixty-seven percent of patients with incomplete intubation of the colon had a prior colonoscopy completed to the cecum (67 percent women, 67 percent men), whereas 50 percent had a follow-up colonoscopy completed to the cecum (56 percent women, 40 percent men). Women, especially those with a history of abdominal hysterectomy, had a significantly lower cecal intubation rate usually because of an impassable sigmoid colon. Prior inability to complete colonoscopy to the cecum does not necessarily forecast future failure.


Antibody testing for cardiac antibody-mediated rejection: which panel correlates best with cardiovascular death?
Recent efforts are being undertaken to update and refine current diagnostic criteria for antibody-mediated rejection (AMR) in heart transplantation. We believe that the appropriate reactants are those that best predict the adverse consequences of AMR and therefore tested various models using different reactants to find the best predictors of cardiovascular mortality in pathologically defined AMR. The study group included only patients in whom all immunofluorescence antibodies of interest had been tested on biopsy specimens obtained after 2002 when C4d was routinely added. We analyzed our data using 3 Cox proportional hazard models with time-varying covariates using an end point of cardiovascular mortality, as previously defined. In 3,712 biopsy specimens from 422 patients, the 2-antibody model achieved a value of R(2) = 0.930 using C3d and C4d antibodies alone. A model that used 4 antibodies--C3d, C4d, human leukocyte antigen-D related (HLA-DR) and fibrin--was superior (R(2) = 0.988). The model that best predicted cardiovascular mortality included all 6 antibodies: HLA-DR, immunoglobulin (Ig) G, IgM, C3d, C4d, and fibrin (R(2) = 0.989). The models using 4 or 6 antibodies were significantly superior to the model using only C3d and C4d (for each interaction, p < 0.0001). The combination of complement components, HLA-DR and fibrin, is valuable in defining AMR in patients at risk for allograft loss from cardiovascular causes. Fibrin is particularly important for detecting the presence of severe AMR, with a high likelihood of poor long-term patient outcome.


Hopes on immunotherapy targeting B7-H3 in neuroblastoma.
Neuroblastoma is one of the most aggressive cancer forms in children, with highly heterogenous clinical manifestations ranging from spontaneous regression to high metastatic capacity. High-risk neuroblastoma has the highest mortality rates of all pediatric cancers, highlighting the urgent need for effective novel therapeutic interventions. B7-H3 immune checkpoint protein is highly expressed in neuroblastoma, and it is involved in oncogenic signaling, tumor cell plasticity, and drug resistance. Immunotherapies based on immune checkpoint inhibition have improved patient survival in several human cancers, and recent reports provide preclinical evidence on the benefits of targeting B7-H3 in neuroblastoma, with emphasis on novel CAR T/NK-cell approaches. Here, we summarize the current status of neuroblastoma targeted therapies, with a focus on B7-H3 as a promising novel immunoregulatory therapeutic target for high-risk neuroblastoma.


Hydrogen peroxide activation of multiple mitogen-activated protein kinases in an oligodendrocyte cell line: role of extracellular signal-regulated kinase in hydrogen peroxide-induced cell death.
Oxidative stress is known to induce cell death in a wide variety of cell types, apparently by modulating intracellular signaling pathways. In this study, we have examined the activation of mitogen-activated protein kinase (MAPK) cascades in relation to oxidant-induced cell death in an oligodendrocyte cell line, central glia-4 (CG4). Exposure of CG4 cells to hydrogen peroxide (H2O2) resulted in an increased tyrosine phosphorylation of several protein species, including the abundantly expressed platelet-derived growth factor (PDGF) receptor and the activation of the three MAPK subgroups, i.e., extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase (JNK). Dose-response studies showed differential sensitivities of PDGF receptor phosphorylation (>1 mM) and ERK/p38 MAPK (>0.5 mM) and JNK (>0.1 mM) activation by H2O2. The activation of ERK was inhibited by PD98059, a specific inhibitor of the upstream kinase, MAPK or ERK kinase (MEK). H2O2 also activated MAPK-activated protein kinase-2, and this activation was blocked by SB203580, a specific inhibitor of p38 MAPK. The oxidant-induced cell death was indicated by morphological changes, decreased 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction, and DNA fragmentation. These effects were suppressed dose-dependently by the MEK inhibitor PD98059. The results demonstrate that H2O2 induces the activation of multiple MAPKs in oligodendrocyte progenitors and that the activation of ERK is associated with oxidant-mediated cytotoxicity.


Horner's syndrome: clinical and radiographic evaluation.
Horner's syndrome (HS) occurs when there is interruption of the oculosympathetic pathway (OSP). This article reviews the anatomy of the OSP and clinical findings associated with lesions located at various positions along this pathway. The imaging findings of lesions associated with HS at various levels of the OSP, classified as preganglionic HS (first- and second-order neuron HS) or postganglionic HS (third-order neuron HS), are demonstrated.


Hyperhidrosis: A Review of Recent Advances in Treatment with Topical Anticholinergics.
Topical anticholinergics have been reported to be effective in managing hyperhidrosis (HH) given the recent approval of glycopyrronium tosylate. This review aimed to examine the effectiveness of emerging topical anticholinergic treatments for HH and their associated adverse effects in comparison to current treatment options. We conducted a search within the PubMed and Embase databases for current and emerging topical anticholinergic treatments for primary HH. The topical anticholinergics that have been recently investigated for use in HH include glycopyrrolate, oxybutynin, sofpironium bromide, and umeclidinium. The only agent currently FDA approved is glycopyrrolate. Knowledge of topical anticholinergic treatment options is important for patient care when managing HH. This review shows that while available safety data thus far are limited, emerging topical anticholinergics pose minimal known human risks.


Impact of upper endoscopic survey during percutaneous endoscopic gastrostomy tube placement.
No consensus exists concerning the utility of a full diagnostic upper endoscopy during percutaneous endoscopic gastrostomy (PEG) tube placement. We evaluate the effect of a complete survey on identifying and treating unsuspected gastrointestinal pathology. During a 10-year period (1990-2000), 1,706 patients underwent attempted PEG tube placement by five different surgical endoscopists at one institution. A complete survey of the esophagus, stomach, and proximal duodenum was attempted in all cases. Endoscopic findings and recommendations were recorded in a computerized log and patient charts. Pathology results were obtained from a computerized pathology database and patient charts. Placement of a PEG tube was successful in 97%, and a full survey was possible in 99% of the cases. Pathologic findings were found in 38% of the surveyed patients (esophagus, 7%; stomach, 24%; duodenum, 7%). One group with gastrointestinal polyps or gastric ulcers (5.7%) was identified as possible candidates for endoscopic intervention. In 30% of this group (1.8% of the total) a biopsy was performed, or bleeding was treated endoscopically. In a second group pathology was identified in the duodenum (6.4%) that would not have been recognized without a full survey. These duodenal findings resulted in a recommendation for treatment change in 38% of this group (2.4% of the total). Upper endoscopic survey before PEG tube placement showed a significant amount of unsuspected gastrointestinal pathology. Findings requiring biopsy, immediate treatment, or a change in medical treatment occurred in 4.2% of the cases, and these findings did not prevent PEG tube placement in any patient.


Interaction of Gut Microbiota and High-Sodium, Low-Potassium Diet in Altering Plasma Triglyceride Profiles Revealed by Lipidomics Analysis.
High sodium and low potassium (HNaLK) intake increases the risk of cardiovascular disease (CVD) and metabolic syndrome. The authors investigate if the dietary minerals interact with the gut microbiota to alter circulating lipid profiles, implicated in CVD and metabolic syndrome. Plasma samples from Wistar rats fed a control or HNaLK diet with or without antibiotic treatment (n = 7 each, a total of 28) are subjected to lipidomics analysis. Lipidomic data are then analyzed using statistical and bioinformatics tools, which detect numerous lipid species altered by the treatments, and consistently demonstrated interactions between the gut microbiota and the HNaLK diet in altering circulating lipids, mainly triglycerides (TGs). Two distinct TG groups differentially regulated by antibiotic treatment are identified. One group (cluster 1), representing the majority of TG species detected, is downregulated, whereas the other group (cluster 2) is upregulated by antibiotic treatment. Interestingly, cluster 2 TGs are also regulated by the diet. Cluster 2 TGs exhibit greater carbon-chain length and double-bond content and include TGs composed of very-long-chain polyunsaturated fatty acids, associated with reduced diabetes risk. The HNaLK diet interacts with gut bacteria to alter plasma lipid profiles, which may be related to its health effects.


Ouabain decreases apparent potassium-conductance in proximal tubules of the amphibian kidney.
According to a previous study from this laboratory, the electrochemical gradient for potassium across the peritubular cell membrane of proximal tubules in the isolated perfused frog kidney increases following the application of ouabain. In order to test, if this phenomenon were due to a decrease of potassium conductance, the effects of ouabain on cell membrane resistances and the sensitivity of the peritubular cell membrane potential difference (PDpt) to step changes of peritubular potassium and bicarbonate concentration were studied. In the absence of ouabain, PDpt averaged -60 +/- 3 mV (n = 25). A step increase of peritubular potassium concentration from 3 to 18 mmol/l (pH 8.07) depolarizes PDpt (delta PDk) by +24 +/- mV (n = 8). An increase of bicarbonate from 20 to 40 mmol/l (pH 8.07) hyperpolarizes PDpt (delta PDb) by -2.8 +/- 0.4 mV (n = 9). The resistance of the luminal and peritubular cell membranes in parallel (Rm) amounts to 45 +/- 9 k omega cm (tubule length) (n = 4) and the voltage divider ratio (VDR) to 1.4 +/- 0.2 (n = 7). The resistance of the cellular cable (cellular core, Rc) approaches 131 +/- 37 M omega/cm (n = 4). Peritubular application of 0.1 mmol/l ouabain leads to a gradual decline of PDpt (t1/2 approx. 30 min), to an increase of Rm, a decrease of delta PDk and an increase of delta PDb. VDR and Rc are not changed significantly. The data point to a functional link between the sodium/potassium ATPase and the potassium conductance of the peritubular cell membrane.


Long-Term Follow-up of Cognitive-Behavioral Therapy for Obsessive-Compulsive Disorder: Symptom Severity and the Role of Exposure 8-10 Years After Inpatient Treatment.
Obsessive-compulsive disorder (OCD) can be effectively treated by cognitive behavioral therapy (CBT) with exposure and response prevention (ERP). Yet, little is known about the long-term effects of inpatient CBT up to one decade after treatment. Thirty patients who had been treated with 12 weeks of intensive inpatient CBT with ERP were examined 8-10 years after their stay in hospital with regard to obsessive-compulsive symptoms, secondary outcomes, and use of healthcare services. Significant (p < .001) improvements in OC symptoms with medium and large effects compared to baseline on the Yale-Brown-Obsessive-Compulsive Scale (Y-BOCS) and on the Obsessive-Compulsive Inventory (OCI-R) could still be observed, with 20% of the patients reaching remission status. Continuation of exposure exercises after the inpatient stay was the sole significant factor for improved scores at follow-up. The results suggest that OCD does not necessarily take a chronic course. However, maintenance of exposure training seems to be crucial for sustained improvement.


The effect of Kinesio Taping on drooling in children with intellectual disability: A double-blind randomized controlled study.
Drooling is an unintentional spillage of saliva, which can be caused by any condition that affects the neuromuscular control of mouth muscles. There are different treatments for drooling, some of which are novel therapies with unknown efficacy like Kinesio Taping (KT). This study aimed to investigate the effects of adding KT to oral-motor training (OMT) on drooling in children with intellectual disability. This is a double-blind randomized controlled trial in which 18 children with intellectual disabilities participated through convenience sampling. Participants were randomly assigned into 2 groups by block randomization method. Kinesio taping of orbicularis oris, supra-hyoid and masseter muscles and routine OMT were performed for the intervention group. The control group received taping with no stretch as placebo. Pre-post assessment was carried out after four weeks of intervention by the drooling rating scale (DRS) and drooling quotient (DQ) test. Within-group analysis showed a significant reduction in drooling post-intervention in both groups based on DRS and DQ (p < 0.001). Between-group analysis indicated a significant improvement in the intervention group (P = 0.008) with moderate effect size using DQ assessment but this difference was not significant with moderate effect size based on parental reports using DRS. DQ assessment revealed that using KT plus OMT can produce greater improvement than sham taping plus OMT. However, there was not a statistically difference between the two groups based on parental reports using DRS. In addition, within-group analysis showed that drooling reduced in both groups after the intervention both based on DRS and DQ assessments. It can be concluded that adding taping with and without stretch to OMT can be considered as a complementary method to mitigate drooling in children with intellectual disabilities.


Fludarabine reduces survivability of HepG2 cells through VEGF under hypoxia.
Fludarabine is the major drug against chronic lymphoblastic leukemia. However, the effects of fludarabine on solid tumors remain unclear. We reported previously that fludarabine inhibited expression of hypoxia-inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in human ovarian cancer cells. The present study aims to investigate, (1) the mechanisms that fludarabine inhibits expression of HIF-1alpha and (2) the effects of fludarabine on tumor cells survival under hypoxia. Human hepatoma HepG2 cells were tested. We found that fludarabine reduced HIF-1alpha stability through prolyl hydroxylation. Fludarabine suppressed hypoxia-induced expression of VEGF and its receptor KDR. It inhibited VEGF-induced activation of AKT and ERK signaling and reduced hypoxia-enhanced HepG2 cell survivability. HepG2 cells were much more sensitive to fludarabine treatment under hypoxia than under nomoxia. These results suggest that fludarabine reduces survivability of HepG2 cells via VEGF signaling under hypoxia.


Ophthalmic findings in patients with autosomal recessive lamellar ichthyosis due to TGM1 mutations in an isolated population.
To describe the ocular clinical characteristics of a group of Mexican patients with lamellar ichthyosis (LI) arising from TGM1 pathogenic variants. Ophthalmological exploration, pedigree analysis and genetic screening were performed in patients with an established clinical diagnosis of lamellar ichthyosis from families located in a small community in the Southeast of Mexico. Nine patients with LI in five families were identified. There were six affected females. All patients (9/9) demonstrated eye lid abnormalities with eight patients showing lid margin abnormalities. Madarosis was present in only three individuals and corneal scarring was documented in two. All nine individuals carried biallelic TGM1 variants, either homozygously or as compound heterozygous. Ocular anomalies are common in individuals with TGM1-related LI. The occurrence of a variety of private or rare mutations hampers the identification of a genotype-phenotype correlation for ocular anomalies in this disorder.


Preoperative Risk Factors for Fibrosarcomatous Transformation in Dermatofibrosarcoma Protuberans.
Dermat of ibrosarcoma protuberans (DFSP) is a soft-tissue sarcoma with a high risk of local recurrence, though typically never metastasizes. DFSP can transform into high-grade fibrosarcoma (DFSP-FS), which has a risk of metastasis. Currently, treatment for DFSP includes Moh's micrographic surgery (MMS); however, this is not recommended for DFSP-FS. Often, the transformation to DFSP-FS is not recognized until the final histological diagnosis. At that point, wide local excision (WLE) of a previous MMS site can be morbid. As such, we analyzed patient risk factors to allow identification of DFSP-FS transformation at presentation. We reviewed 368 (174 female, 194 male) patients with a mean age of 42 years from two sarcoma centers. A total of 319 (87%) patients had a history of DFSP and 49 (13%) had DFSP-FS. When comparing patients with a DFSP to those with a DFSP-FS, patients with a DFSP-FS were more likely (p<0.05) to be older, female and with larger tumors. A painful mass and rapidly enlarging mass were associated with DFSP-FS. Patients who presented with DFSP-FS were found to typically have a larger, painful, and growing mass. Patients with these features should be referred for WLE over MMS at presentation.


Analysis of patients with congenital diaphragmatic hernia requiring pre-operative extracorporeal membrane oxygenation (ECMO).
The purpose of this report was to analyze the patients requiring preoperative extracorporeal membrane oxygenation (ECMO) as the most critical group of patients with congenital diaphragmatic hernia (CDH) and to identify any special features. Over the past 11 years, out of 72 neonates with CDH admitted before 24 h of age, 40 (56%) could be managed with conventional therapies while the other 32 (44%) required ECMO. Seventeen infants requiring preoperative ECMO were classified as group 1, and the 15 with postoperative ECMO as group 2 (controls). The records of patients in both groups were analyzed. Patients in group 1 were not only severely hypoxic, but also significantly hypercapneic on admission, and in 14 (82%) the diaphragmatic defect was so large or totally agenetic that a prosthetic patch was necessary. The average age at onset of ECMO in group 1 was 13.1 h, and the average duration was 159 h. Major hemorrhagic complications including intracranial hemorrhage occurred with a significantly higher frequency in group 1. The survival rate in group 1 was 41%, compared with 73% in group 2 and 85% in non-ECMO patients. Four infants in group 1 with extremely hypoplastic lungs could not be weaned from ECMO, and died without undergoing an operation. Moreover, 4 of the 7 survivors in group 1 required prolonged (105-658 days) ventilator care with a tracheostomy after weaning from ECMO, and were frequently hospitalized thereafter. The pulmonary function of these patients remained severely underdeveloped for a long time; indeed, the average pulmonary perfusion ratio of the affected side remained at only 40% of the contralateral side in group 1, although the volume ratio reached 85%. These findings may suggest that the main pathology of the patients requiring preoperative ECMO was a high degree of pulmonary hypoplasia, and that there will be limitations to management using ECMO.


Common measures, better outcomes (COMBO): a field test of brief health behavior measures in primary care.
Primary care offices have been characterized as underutilized settings for routinely addressing health behaviors that contribute to premature death and unnecessary suffering. Practical tools are needed to routinely assess multiple health risk behaviors among diverse primary care patients. The performance of a brief set of behavioral measures used in primary care practice is reported here. Between August 2005 and January 2007, 75 primary care practices assessed four health behaviors, using a 21-item patient self-report questionnaire for adults or a 16-item questionnaire for adolescents. Data were collected via telephone, paper, or electronic means, either with or without assistance. The performance of these measures was evaluated by describing risk-behavior prevalences, combinations of risk behaviors, and missing data. Of 227 adolescents and 5358 adults, most patients completed all of the survey questions. Two or more unhealthy behaviors were reported by 47.1% of adolescents and 69.2% of adults. Percentages of adults who completed all the survey items varied by health behavior: tobacco use, 98.5%; diet, 98.2%; physical activity, 96.2%; alcohol use, 85.1%. Missing data rates were higher for unassisted patient self-reporting. A relatively brief set of health behavior measures was usable in a variety of primary care settings with adults and adolescents. The performance of these measures was uneven across behaviors and administration modes, but yielded estimates of unhealthy behaviors consistent overall with what would be expected based on published population estimates. Further work is needed on measures for alcohol use and physical activity to bring practical assessment tools for key health behaviors to routine primary care practice.


CRAC Channel Components Quantitative Expression (In Tissues and Cell Lines) Using qPCR.
Since last decade real-time qPCR has become a routine and robust approach for measuring the expression of genes of interest. Indeed, using qPCR, expression profile analyses are now possible and participate to the understanding of physiological or pathological role of channels such as calcium release-activated channels (CRAC). Initially discovered in lymphocyte T and immunity perturbations, recent studies have highlighted the role of CRAC channels in other pathologies such as cancer. Here we describe a protocol to quantify CRAC components expression, in tissue sample and cell lines, to validate knockdown strategies or identify their roles in physiological and pathological conditions (Hoth and Penner, J Physiol 465:359-386, 1993; Hoth and Penner, Nature 355:353-356, 1992; and Zweifach and Lewis, Proc Natl Acad Sci U S A 90:6295-6299, 1993).


Catheter-free geriatric care. Routines and consequences for clinical infection, care and economy.
In a geriatric hospital the routines of one ward were modified with the intention of removing indwelling catheters from all patients admitted to the ward. A continence training programme had been designed during the preceding 6 months. A total of 124 patients were admitted with indwelling catheters during a period of 18 months. It was possible to remove the catheters in 117 of these. Patients and their relatives reacted favourably to catheter-free care. The attitude of ward staff also was positive. The overall nursing requirements did not increase. Antibiotic prescription was 90 per cent less than in the control wards. This difference was accounted for not only by a reduction in drugs used against urinary tract infections, but also by a lower consumption of agents mainly used in the treatment of septicaemia, bronchopneumonia and wound infection. The cost of laundry and of hygiene and storage articles, including catheters, absorbing pads and other incontinence aids was 46 per cent of that in the control wards. Four years later, 65 per cent and 72 per cent of the patients from the test and control wards respectively, had died. Of the surviving patients from the test ward 78 per cent were still catheter-free.


Does the beta2-agonist clenbuterol help to maintain myocardial potential to recover during mechanical unloading?
Chronic mechanical unloading induces left ventricular (LV) atrophy, which may impair functional recovery during support with an LV-assist device. Clenbuterol, a beta2-adrenergic receptor (AR) agonist, is known to induce myocardial hypertrophy and might prevent LV atrophy during LV unloading. Furthermore, beta2-AR stimulation is reported to improve Ca2+ handling and contribute to antiapoptosis. However, there is little information on the effects of clenbuterol during LV unloading. We investigated LV atrophy and function after LV unloading produced by heterotopic heart transplantation in isogenic rats. After transplantation, rats were randomized to 1 of 2 groups (n=10 each). The clenbuterol group received 2 mg.kg(-1).d(-1) of the drug for 2 weeks; the control group received normal saline. The weight of unloaded control hearts was 48% less than that of host hearts after 2 weeks of unloading. Clenbuterol significantly increased the weight of the host hearts but did not prevent unloading-induced LV atrophy. Papillary muscles were isolated and stimulated, and there was no difference in developed tension between the 2 groups. However, the inotropic response to the beta-AR agonist isoproterenol significantly improved in the clenbuterol group. The mRNA expression of myocardial sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a) and fetal gene shift (myosin heavy chain [MHC] mRNA isozyme) was also significantly improved by clenbuterol treatment. There was no difference in beta1-AR mRNA expression between the 2 groups. In contrast, beta2-AR mRNA was significantly decreased in the clenbuterol-treated, unloaded heart. This indicates that clenbuterol may downregulate beta2-ARs. In the evaluation of apoptosis, mRNA expression of caspase-3, which is the central pathway for apoptosis, tended to be better in the clenbuterol group. During complete LV unloading, clenbuterol did not prevent myocardial atrophy but improved gene expression (SERCA2a, beta-MHC) and beta-adrenergic responsiveness and potentially prevented myocardial apoptosis. However, chronic administration of clenbuterol may be associated with downregulation of beta2-ARs.


Nickel-iron-driven heterogenous bio-electro-fenton process for the degradation of methylparaben.
Discharge of emerging contaminants such as parabens in natural water bodies is a grievous concern. Among parabens, methylparaben (MP) is most prevalent due to its extensive usage in personal care and food products and has been purported to trigger hormonal-related diseases. In this regard, the bio-electro-Fenton (BEF) process garners attention for remediating refractory compounds because of its ability to generate in situ hydroxyl radicals (•OH) utilising the energy harvested from electroactive microorganisms. In the present investigation, a Ni-Fe-driven heterogenous BEF system (BEF-MFC) was used to degrade MP from different matrices. At neutral catholyte pH, 99.54 ± 0.22% of MP was removed from an initial concentration of 10 mg/L in 240 min of retention time with an estimated treatment cost of about 1.01 $/m3. The removal rate ameliorated when the catholyte pH was dropped to 3.0 and by imposing an external voltage of 0.5 V, requiring just 120 min to achieve comparable MP removal efficiencies. However, catalyst leaching was higher at acidic pH (leaching of Fe ions = 0.44 mg/L and Ni ions = 0.06 mg/L) and applying external voltage increased the treatment cost slightly to 1.08 $/m3. Further, treatment of 10 mg/L MP-spiked real wastewater at pH of 7.0 with the BEF-MFC attained 85.70 ± 3.30% and 56.50 ± 1.70% reduction in MP and total organic carbon, respectively, in 240 min. In addition, a maximum power density of 205.90 ± 2.27 mW/cm2 was harvested in the BEF-MFC; thus, portraying the dual benefit of Ni-Fe heterogeneous catalyst. Even though, Ni-Fe performed reasonably well as Fenton-cum-cathode catalyst, future endeavours should be poised to fine-tune catalysts to accelerate H2O2 and •OH generation, which will reinforce the scalability of this system.


Stroke-prone renovascular hypertensive rat as an animal model for stroke studies: from artery to brain.
High blood pressure is a main risk factor for both initial and recurrent stroke. Compared to the post stroke situation in normotension, the brain lesion is larger in hypertension, and the treatments may not be as effective. Thus, the results from healthy individuals may not be directly applied to the hypertensive. In fact, the high prevalence of hypertension in stroke patients and its devastating effect urge the necessity to integrate arterial hypertension in the study of stroke in order to better mimic the clinical situations. The first step to do so is to have an appropriate hypertensive animal model for stroke studies. Stroke-prone renovascular hypertensive rat (RHRSP) introduced in 1998, is an animal model with acquired hypertension independent of genetic deficiency. The blood pressure begins to increase during the first week after constriction of bilateral renal arteries, and becomes sustained since around the 3rd month. Because the morphological and physiological changes of cerebral arteries are similar to those in hypertensive patients, the rats represent a higher than 60% incidence of spontaneous stroke. The animal model has several advantages: one hundred percent development of hypertension without gene modification, high similarity to human hypertension in cerebrovascular pathology and physiology, and easy establishment with low cost. Thus, the model has been extensively used in the investigation of ischemic stroke, and has been shown as a reliable animal model. This paper reviewed the features of RHRSP and its applications in the treatment and prevention of stroke, as well as the investigations of secondary lesions postischemic stroke.


Effect of early breast milk expression on milk volume and timing of lactogenesis stage II among mothers of very low birth weight infants: a pilot study.
The purpose of this randomized pilot study was to collect preliminary data regarding the feasibility and effects of early initiation of milk expression on the onset of lactogenesis stage II and milk volume in mothers of very low birth weight (VLBW) infants. Twenty women were randomized to initiate milk expression within 60 min (group 1) or 1 to 6 h (group 2) following delivery. Milk volume and timing of lactogenesis stage II was compared between groups using Wilcoxon's rank sum tests. Group 1 produced statistically significantly more milk than group 2 during the first 7 days (P=0.05) and at week 3 (P=0.01). Group 1 also demonstrated a significantly earlier lactogenesis stage II (P=0.03). Initiation of milk expression within 1 h following delivery increases milk volume and decreases time to lactogenesis stage II in mothers of VLBW infants.


Concentrations of homovanillic acid and 5-hydroxyindoleacetic acid in cerebrospinal fluid from human infants in the perinatal period.
To assess maturation of central serotonin and catecholamine pathways at birth, we measured lumbar CSF homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), stable acid metabolites of dopamine and serotonin, using HPLC with electrochemical detection. CSFs from 57 neonates (38 premature and 19 at term) and 13 infants 1-6 months old were studied. HVA levels increased with maturity (p less than 0.05; ANOVA), whereas 5-HIAA levels were similar in all these subjects. HVA/5-HIAA ratios increased markedly from 1 +/- 0.12 in the most premature neonates to 1.98 +/- 0.17 in the older infants (p less than 0.01; t test). There were no sex differences for these values.


Effect of somatostatin (SRIF) on plasma glucose and insulin response to glucagon in liver cirrhosis.
The present study was performed in order to evaluate the plasma glucose pattern in cirrhotic patients who, in the course of a continuous somatostatin infusion (500 microgram/h), were given pulses of glucagon (1 mg i.v.). In normal as well as in cirrhotic subjects somatostatin infusion provoked a marked reduction of the IRI plasma level and this was uninfluenced by subsequent glucagon administration. The rise in plasma glucose level in response to i.v. glucagon administration during somatostatin infusion was less marked in cirrhotics compared to normal subjects. This can be attributed to a variety of factors such as reduced number of liver cells or quantitative or qualitative changes of the liver cell glucagon receptors. Glucagon does not seem to contribute to the pathogenesis of carbohydrate intolerance in liver cirrhosis.


Antibodies from primary humoral responses modulate the recruitment of naive B cells during secondary responses.
Vaccines generate high-affinity antibodies by recruiting antigen-specific B cells to germinal centers (GCs), but the mechanisms governing the recruitment to GCs on secondary challenges remain unclear. Here, using preclinical SARS-CoV and HIV mouse models, we demonstrated that the antibodies elicited during primary humoral responses shaped the naive B cell recruitment to GCs during secondary exposures. The antibodies from primary responses could either enhance or, conversely, restrict the GC participation of naive B cells: broad-binding, low-affinity, and low-titer antibodies enhanced recruitment, whereas, by contrast, the high titers of high-affinity, mono-epitope-specific antibodies attenuated cognate naive B cell recruitment. Thus, the directionality and intensity of that effect was determined by antibody concentration, affinity, and epitope specificity. Circulating antibodies can, therefore, be important determinants of antigen immunogenicity. Future vaccines may need to overcome-or could, alternatively, leverage-the effects of circulating primary antibodies on subsequent naive B cell recruitment.


Neuroprostanes, produced by free-radical mediated peroxidation of DHA, inhibit the inflammatory response of human macrophages.
The anti-inflammatory properties of DHA have been largely demonstrated in vitro and in vivo but research gaps remain regarding the contribution of the oxygenated metabolites. Among them, we are focusing on prostaglandin-like molecules termed Neuroprostanes (NeuroPs) which are produced through free-radical-mediated peroxidation of DHA. We hypothesized that these specific molecules which are highly reactive and produced in abundance during oxidative stress and inflammation could contribute to the anti-inflammatory properties of DHA. Human peripheral blood mononuclear cells were isolated from healthy donors by Ficoll density gradient centrifugation. Monocytes were differentiated into resting macrophages (RM) for 6 days (37°C, 5% CO2). RM were exposed to 2 different types of NeuroPs (i.e. 14-A4-NeuroP and 4-F4t-NeuroP, 10µM) or ethanol (vehicle 0.15%) during 30min. Then LPS (100ng/mL) was added for 6hours to induced inflammatory response. Both types of NeuroPs (14-A4-NeuroP and 4-F4t-NeuroP) significantly decreased the mRNA levels of IL-6 (-49% and -26% respectively) and MCP-1 (-55% and -24% respectively). Secretion of TNFα and MCP-1 was also reduced when RM were exposed to 14-A4-NeuroP (-10%, ns and -34%, p<0.05) and 4-F4t-NeuroP (-12%, p<0.01 and 25%, ns). Preliminary results regarding the expression and phosphorylation of IkBa suggest that 4-F4t-NeuroP could exert its anti-inflammatory effects through the inhibition of IkBa phosphorylation. Finally, cotransfection of luciferase reporter vector with hPPARg expression vector performed on Cos-7 cells suggests that NeuroPs probably act independently of PPARg. In conclusion, these results suggest that the anti-inflammatory properties of DHA could be mediated, at least in part, by NeuroPs which corroborates the importance of oxidative stress in cell signaling.


Eighty years of Medication-Overuse Headache: what about Medication-Overuse Backpain?
Although chronic low back pain (CLBP) is one of the most common pain syndromes, up to now, clear pathophysiological causes or specific treatment options are missing. Medication-overuse has been associated with chronic headache, but never with CLBP. Based on several similarities between CLBP and Medication-Overuse Headache (MOH), we hypothesized that medication-overuse might contribute to CLBP as well, maybe even as an own entity. Might there be something like Medication-Overuse Backpain (MOB)? We substantiate our hypothesis with a preliminary case-series analyzing five patients suffering from CLBP with a marked medication-overuse. In these patients, a stepwise analgesic withdrawal was recommended. Within 6 months of recruitment, five patients fulfilled the inclusion criteria and successfully completed discontinuation of their medication. All patients reported noticeable pain relief, despite the discontinuation of their analgesics. Withdrawal was well tolerated in all cases. Considering our results, the described withdrawal method seems to be a simple and safe method to achieve pain reduction while simultaneously preventing organ damage. Despite the preliminary character of our results, our hypothesis might stimulate a new understanding of CLBP's pathophysiology.


Involving patients in undergraduate health professions education: What's in it for them?
Patients have become more involved in research, policy, and health professions education. They are involved in teaching students competencies required for person-centred care, but patient benefits have not received proper attention. This exploratory study identifies how patient involvement in health professions education help patients to practice self-management and shared decision-making. Individual interviews were conducted with patients (hereafter 'experts by experience') (N = 11) who participated in the Patient As a Person Module, organised for students of health professions in The Netherlands. Additionally, one of their healthcare professionals (N = 10) and family members (N = 9) were interviewed. Directed content analysis was used. Participants reported that sharing lived experiences helped experts by experience to reflect on their preferences regarding health and healthcare, accept their changed selves, and obtain a renewed sense of purpose. They reported gaining insight into the perspectives of healthcare professionals, which yielded more equal healthcare professional-patient relationships. Sharing their lived experiences with health and health care with students could help patients in practising effective self-management and participate in shared decision-making. Approaching patient involvement in health professions education from both the perspectives of students and experts by experience, as opposed to students alone, optimises its societal impact.


Evaluation of hyaluronic acid sheet for the prevention of postlaminectomy adhesions.
Various materials have been tested for their ability to maintain a barrier between muscles and epidural space in order to physically or chemically inhibit scar ingrowths. Hyaluronic acid (HA) solution and gel have been reported to be effective in preventing adhesions postlaminectomy; however, neither has been used clinically after spinal surgery. To determine the efficacy of HA sheet for the prevention of postlaminectomy adhesions compared with that of HA gel or another sheet. An animal model of lumbar laminectomy in rabbits was used to study postoperative scar tissue formation around the spinal cord. The histologic effects of HA sheet were compared with those of Gelfoam (GF) and further evaluated by an inflammation model using rhTNF-alpha. Rabbit. Histologic examination. Five rabbits were killed at 2, 4, 8, and 24 weeks after laminectomy, respectively. Another 18 rabbits were examined in an environment of active inflammation experimentally induced by rhTNF-alpha to compare the effects of HA sheet with those of GF or HA gel. Histologic examination was performed to quantitatively assess invasive scar formation or inflammation postlaminectomy, and then, the histologic effects of HA sheet were compared with those of GF or HA gel. In the HA group, significantly, the area of subarachnoid space was larger, distance from the surface of dura to scar tissues was greater, the number of inflammatory cells in the scar tissues at the site of laminectomy was less, and enlargement of dura was suppressed. Using an inflammation model, we also demonstrated the efficacy of HA sheet treatment. In an experimental laminectomy model, HA sheet formed a solid interpositional membrane barrier and exhibited anti-inflammatory activity. Further investigations will be needed for HA sheet to be used clinically.


Human Papillomavirus-Associated Oropharyngeal Cancer: Global Epidemiology and Public Policy Implications.
Global trends in human papillomavirus (HPV)-associated head and neck cancers (HNC), specifically in the oropharynx subsite, have been dynamically changing, leading to new staging and treatment paradigms. Epidemiologic studies have noted regional variations in HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). While HPV vaccination remains the main preventative approach, vaccination policy in relation to gender neutrality is heterogeneous and particularly sparse in low- and middle-income countries, where the burden of global cancer cases and HPV-associated HNC are not well-characterized in certain regions. This review summarizes the existing literature on regional variations of HPV-associated OPSCC and gender-neutral vaccine policies. Based on available data, the incidence of HPV-associated OPSCC is highest in North America, Europe, and Oceania. As of 2022, 122 of 195 (63%) World Health Organization (WHO) member states had incorporated HPV vaccinations nationally; of these, 41 of 122 (34%) member states have introduced gender-neutral vaccine coverage. Future research is needed to describe continued evolving trends in HPV-associated OPSCC, understand underlying risk factors leading to regional variation in disease, and implement gender-neutral policy more broadly.


Demand pacemaker slowing: a simple bedside technique.
We present a simple noninvasive bedside technique to slow gradually any R-wave inhibited ventricular demand pacemaker up to one-half its original rate for indefinite periods of time. Gradual pacemaker slowing allows accurate diagnostic observations and therapeutic interventions in pacemaker-induced arrhythmias and may possibly be used in the management of unstable angina in patients with ventricular demand pacemakers.


Effects of eight weeks of exercise training and orlistat therapy on body composition and maximal exercise capacity in obese females.
A comparative assessment was made of the short-term effects of orlistat therapy and exercise training on body composition and aerobic fitness in obese females. A total of 24 obese patients were enrolled in to the study; 12 received orlistat therapy (DO) and 12 participated in a regular aerobic exercise-training programme (DE). All patients were on hypocaloric diets. Each patient performed three incremental ramp exercise tests (one at Week 0, one at the end of Week 4 and one at the end of Week 8) to exhaustion using an electromagnetically braked cycle ergometer to determine their anaerobic threshold and maximal exercise (Wmax) capacity. Patients in the DE group performed continuous exercise at a work rate that corresponded to the anaerobic threshold. Weight loss and loss of fat mass after 8 weeks were -6.4% (P=0.002) and -13.4% (DE) vs -5.8% (P=0.002) and -6.4% (P=0.008) (DO), respectively. Wmax capacity was 90.8+/-5 W (basal) vs 92.9+/-5 W (Week 4, P=0.1) and 100.4+/-6 W (Week 8, 10.5%, P=0.04) in the DO group, and 96.2+/-6 W (basal) vs 129.1+/-4 W (Week 4, 34.1%, P=0.002) and 137.5+/-5 W(Week 8, 42.9%, P=0.002) in the DE group. Despite similar decreases in body weight in both groups, patients in the DE group achieved a markedly higher level of Wmax, reflecting a better improvement in cardiopulmonary fitness, compared with patients in the DO group. Considering the improvement of aerobic fitness in the short term, an aerobic exercise-training programme should be considered for sedentary obese patients to improve their aerobic fitness and thereby reduce the negative outcomes of obesity.


Thickness-dependent in-plane anisotropy of GaTe phonons.
Gallium Telluride (GaTe), a layered material with monoclinic crystal structure, has recently attracted a lot of attention due to its unique physical properties and potential applications for angle-resolved photonics and electronics, where optical anisotropies are important. Despite a few reports on the in-plane anisotropies of GaTe, a comprehensive understanding of them remained unsatisfactory to date. In this work, we investigated thickness-dependent in-plane anisotropies of the 13 Raman-active modes and one Raman-inactive mode of GaTe by using angle-resolved polarized Raman spectroscopy, under both parallel and perpendicular polarization configurations in the spectral range from 20 to 300 cm-1. Raman modes of GaTe revealed distinctly different thickness-dependent anisotropies in parallel polarization configuration while nearly unchanged for the perpendicular configuration. Especially, three Ag modes at 40.2 ([Formula: see text]), 152.5 ([Formula: see text]), and 283.8 ([Formula: see text]) cm-1 exhibited an evident variation in anisotropic behavior as decreasing thickness down to 9 nm. The observed anisotropies were thoroughly explained by adopting the calculated interference effect and the semiclassical complex Raman tensor analysis.


The novel complement inhibitor human CUB and Sushi multiple domains 1 (CSMD1) protein promotes factor I-mediated degradation of C4b and C3b and inhibits the membrane attack complex assembly.
CUB and Sushi multiple domains 1 (CSMD1) is a transmembrane protein containing 15 consecutive complement control protein (CCP) domains, which are characteristic for complement inhibitors. We expressed a membrane-bound fragment of human CSMD1 composed of the 15 C-terminal CCP domains and demonstrated that it inhibits deposition of C3b by the classical pathway on the surface of Chinese hamster ovary cells by 70% at 6% serum and of C9 (component of membrane attack complex) by 90% at 1.25% serum. Furthermore, this fragment of CSMD1 served as a cofactor to factor I-mediated degradation of C3b. In all functional assays performed, well-characterized complement inhibitors were used as positive controls, whereas Coxsackie adenovirus receptor, a protein with no effect on complement, was a negative control. Moreover, attenuation of expression in human T47 breast cancer cells that express endogenous CSMD1 significantly increased C3b deposition on these cells by 45% at 8% serum compared with that for the controls. Furthermore, by expressing a soluble 17-21 CCP fragment of CSMD1, we found that CSMD1 inhibits complement by promoting factor I-mediated C4b/C3b degradation and inhibition of MAC assembly at the level of C7. Our results revealed a novel complement inhibitor for the classical and lectin pathways.


Preparation of Bordetella pertussis DNA from respiratory samples for real-time PCR by commercial kits.
Bordetella pertussis is increasingly detected by real-time PCR, but most kits for extracting Bordetella-DNA from respiratory samples are not validated for this material. Respiratory clinical materials were spiked with Bordetella pertussis cells. Four ion-exchange chromatography methods from one manufacturer were used for DNA preparation. Two real-time PCRs detecting the IS481 of Bordetella pertussis and based either on a hybridisation probes format (LightCycler) or on a TaqMan format were used. All kits effectively prepared DNA for Bordetella pertussis real-time PCR. The procedures were linear over a broad range, and the lower level of sensitivity was similar. Sensitivities measured as CT values were different. Inter-assay CVs were between 6.8% and 17.3%. Two kits did not effectively remove inhibitory substances from the respiratory samples. Commercial kits are useful for preparing Bordetella pertussis DNA from respiratory samples, but even kits from one manufacturer show significant differences in effectiveness and removal of inhibitory substances.


A kinetic-based stopped-flow DPPH• method.
The reaction kinetics of antioxidants with free radicals is crucial to screen their functionality. However, studying antioxidant-radical interactions is very challenging for fast electron-donor substances, such as ascorbic acid, because the reaction ends in a few seconds. Accordingly, this work proposes a rapid and sensitive method for the determination of the absolute rate constant of the reaction between fast antioxidants and DPPH•. The method consists of a stopped-flow spectrophotometric system, which monitors the decay of DPPH• during its interaction with antioxidants. A kinetic-based reaction mechanism fits the experimental data. Kinetic parameters include a second order kinetics (k1) and, depending on the type of antioxidant, a side reaction (k2). Ascorbic acid was the fastest antioxidant (k1 = 21,100 ± 570 M-1 s-1) in comparison with other eleven phenols, showing k1 values from 45 to 3070 M-1 s-1. Compounds like catechin, epicatechin, quercetin, rutin, and tannic, ellagic and syringic acids presented a side reaction (k2 from 15 to 60 M-1 s-1). Among seven fruit juices, strawberry was the fastest, while red plum the slowest. Overall, the proposed kinetic-based DPPH• method is simple, rapid, and suitable for studying the activity and capacity of different molecules, and food samples rich in fast antioxidants, like fruit juices.


Pancreatic disorders in infancy and childhood: experience with 92 cases.
Ninety-two children with pancreatic disorders were treated over a 10-year period. Thirty-three had blunt trauma, while 69 had medical, metabolic, or neoplastic diseases. Children with trauma had either duct disruption (3), gland fracture (4), or pseudocysts formation (26). Operation was required in 30. Pseudocysts were treated with observation alone in three cases, ultrasound-guided percutaneous aspiration in three, surgical external drainage in two, distal pancreatectomy in four, cyst gastrostomy in ten, and cyst-Roux-en-Y jejunostomy in six. Other disorders included pancreatitis (44), neoplasms (10), nesidioblastosis (4), and pancreaticosplenic abscess (2). Treatment for neoplasms included surgical excision in nine and biopsy in one (adenocarcinoma). Patients with nesidioblastosis underwent 95% (near total) pancreatic resection (two after previous unsuccessful 80% resection). Pancreatitis was familial in two cases, necrotizing in two, idiopathic in 11, and secondary to medications in six cases (steroids, 2; L-asparaginase, 4), gallstones in 17, and choledochal cysts in 6. Pancreatitis resolved after observation and conservative therapy in ten idiopathic cases, 4/6 medication-related cases, and following correction of biliary tract disease (15/17) or choledochal cysts (6). Pancreatic resection or drainage was required in the remaining cases. Pancreatic disorders can be accurately detected with computed tomography (CT) scan in most cases (excluding insulinoma). Ultrasound (US) is useful in cases of biliary tract disease and pseudocyst formation. Traumatic pseudocysts can resolve spontaneously or with US-guided percutaneous drainage (in the presence of normal ducts). Children with neoplasms, abnormal pancreatic ducts, or recurrent pancreatitis require resection or appropriate drainage procedures. Overall survival was 95%.


Removal of sialic acids from the purified insulin receptor results in enhanced insulin-binding and kinase activities.
Neuraminidase treatment of the purified insulin receptor resulted in an increase in both insulin-binding and kinase activities. Neuraminidase-treated alpha and beta subunits moved further than native subunits on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. The enhancement of insulin-binding and kinase activities and increased mobility of the subunits on SDS-PAGE were not observed when the receptor was treated with neuraminidase in the presence of neuraminidase inhibitor. These results suggest that terminal sialic acid residues have a significant role in insulin-binding and kinase activities. The involvement of sialic acid residues in the activities of the receptor has not been detected by previous studies.


Familial retinoschisis in female patients.
We report two female patients, a mother and daughter, with bilateral foveal changes that resembled those of X-linked recessive juvenile retinoschisis. The 23-year-old daughter had flat retinoschisis at the temporal periphery with multiple small inner-layer breaks in both eyes. There was foveal retinoschisis with fine radial folds. The optic disc was dragged to the nasal side. The 49-year-old mother also had foveal retinoschisis in each eye but there was no peripheral retinoschisis. In the left eye several retinal breaks with minimal retinal detachment were found. Electrophysiological findings in both cases were similar. Single-flash electroretinogram (ERG) showed normal a-wave and decreased b-wave, presenting a negative shape. Averaged scotopic and photopic ERGs showed slightly reduced b-waves, but they were within normal ranges. Visually evoked potentials were subnormal. Ophthalmoscopic and electrophysiologic findings were compatible with X-linked recessive juvenile retinoschisis, but an autosomal dominant inheritance was most likely. Our cases do not follow previously reported characteristics and may represent a new clinical entity.


Delayed foreign-body reaction to silk sutures in pediatric neurosurgical patients.
Nonabsorbable silk sutures have been a frequently used foreign material in neurosurgery. In general, they are reliable and safe with minimal bio-incompatibility. Three pediatric neurosurgical patients came to clinical attention, however, because of delayed foreign-body reactions to silk sutures. The delayed atypical presentation of these patients delayed appropriate diagnosis and therapy. In two patients, the reaction presented as a delayed inflammation 7 years following surgical suture placement. In the other patient, the reaction caused delayed recurrent shunt failures and surgical wound breakdown. These three cases are used to introduce a discussion of the delayed response of the host to foreign material and its pertinence to neurosurgery.


Anti-Saccharomyces cerevisiae antibodies are associated with the development of postoperative fistulas following ileal pouch-anal anastomosis.
Although serologic testing for perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) is reportedly useful in distinguishing ulcerative colitis (UC) from Crohn's disease (CD), there are few and conflicting reports assessing their utility in predicting postoperative complications after ileal pouch-anal anastomosis (IPAA). We examined the associations between postoperative complications such as pouchitis or fistulas and pANCA and ASCA antibodies in a group of patients who underwent IPAA for UC. We conducted a retrospective chart review of 34 patients initially diagnosed with UC (four of these patients had a diagnosis of indeterminate colitis) who underwent IPAA by a single surgeon, and who had pANCA and ASCA antibody levels measured during their clinical course. Study patients were assigned to four groups based on the pattern of antibody reactivity: pANCA+/ASCA- (16 patients), pANCA-/ASCA+ (nine patients), pANCA+/ASCA+ (five patients), and pANCA-/ASCA- (four patients). The median length of follow-up was 16 months (3-144 months). None of the patients (0 of 16) who were pANCA+/ASCA- had their preoperative diagnosis of UC changed after a median follow-up of 14 months (3-118 months). Of the nine patients with a preoperative diagnosis of UC who were pANCA-/ASCA+, four patients (44%) had their diagnosis changed postoperatively to CD based on clinical findings, with a median follow-up: 15 months (5-98 months). Of 16 patients who underwent IPAA and who were pANCA+/ASCA-, 15 of 16 (93.75%), were free of fistulas postoperatively, with a median follow-up of 14 months (3-118 months). Of nine patients with a preoperative diagnosis of UC who underwent IPAA and who were pANCA-/ASCA+, four of nine (44%; p = 0.04) developed fistulas postoperatively, with a median length of follow-up of 55 months (15-67 months). No relationship between serologic profiles or antibody titer levels and the development of pouchitis was identified. In a cohort of patients undergoing IPAA for UC, serologic profiles may be useful in identifying patients at risk of postoperative fistula formation. Patients who were pANCA-/ASCA+ were at increased risk for the development of fistulas postoperatively compared to patients who were pANCA+/ASCA-, and were also more likely to have their diagnosis changed postoperatively to CD. A larger study is needed to validate these observations.


Extrarenal Wilms tumor.
The previous reports of extrarenal Wilms tumor are reviewed and two additional patients presented. The clinical and pathologic features are discussed. The diagnosis of extrarenal Wilms tumor does not imply a bad prognosis. Treatment should utilize multidrug chemotherapy similar to the guidelines set by the National Wilms Tumor Study.


DNA replication and repair in ataxia telangiectasia cells exposed to bleomycin.
A marked increase in sensitivity to bleomycin was observed in two ataxia telangiectasia (AT) lymphoblastoid cell lines compared to that in cell lines from two normal individuals. This sensitivity was obtained at two different concentrations of bleomycin. While normal cells showed a rapid recovery of ability to divide, there was no indication of such a recovery in AT cells up to 120 h after bleomycin treatment. A similar level of breakage of DNA occurred in both cell types after incubation with bleomycin. The rate of repair of these breaks was also the same. DNA synthesis was found to be more resistant to bleomycin in AT cells than in control cells. The latter data are in keeping with results previously obtained using ionizing radiation.