[When should the anti-glaucoma treatment start?].
The decision to start a glaucoma treatment in a newly diagnosed patient is easy when the disease is clearly identified with typical optic nerve cupping, visual field defect, and elevated intraocular pressure. However it often appears more complicated, especially in young patients for whom a careful analysis of the fundus and an examination of nerve fiber layers should be assessed to detect an early sign of glaucoma before any visual field change. If glaucoma is present, patients with intraocular pressure above 14 mmHg should be treated, as in such cases there is always a "pressure risk factor". In case of isolated elevated ocular pressure, in France it is usually considered that a pressure above 25 mmHg should be reduced, with a target pressure at least of--20% from baseline. Other factors should also be considered such as quality of life and cost of the treatment. The psychological profile of the patient should also be taken in to account and clear information concerning the risks and potential severity of the disease should be given before the onset of treatment.


Biomechanical model of knee collateral ligament injury with six degrees of freedom.
Knee ligament injuries cannot be fully described using simplified joint models or by experimentation alone. The study objective was to model the contributions of the collateral ligaments over six degrees of freedom (DOF) of knee joint articulation to aid the diagnosis of knee ligament injuries. A kinematic model of the knee joint with six DOF was developed using the Musculoskeletal Joint Modeller software, and the effects of medial collateral ligament (MCL) and lateral collateral ligament (LCL) rupture were evaluated. The centres of mass of the tibia and femur were determined from their surface geometry, and the displacement of the moving tibia was determined by measuring the displacements of the attached ligaments with respect to its centre of mass. Compared to an intact knee, a tibia without the LCL had higher medial translation and lower valgus rotation, while a tibia without the MCL had higher lateral translation and higher valgus rotation. At 0°, 30° and 60° of flexion, the tibia without the LCL had more internal rotation than an intact knee. Understanding the complete kinematics of knee joints may improve the diagnosis of ligament injuries and guide tissue replacement surgery. Predicting joint behaviour in the clinic after treatment might benefit from a combined modelling approach that includes both clinicians and basic researchers.


Abnormal spontaneous brain activity in type 2 diabetic retinopathy revealed by amplitude of low-frequency fluctuations: a resting-state fMRI study.
To explore the altered spontaneous cerebral activity patterns and impaired functional regions in patients with diabetic retinopathy (DR) using resting-state functional magnetic resonance imaging (rs-fMRI) based on the amplitude of low-frequency fluctuations (ALFF) algorithm. Twenty-one patients with DR (mean age, 54.9±9.9 years; 11 females) and 17 healthy control subjects (54.8±5.7 years; 9 females) were prospectively studied. The DR patients underwent laboratory tests. All individuals underwent a neuropsychological test. The differences in the ALFF values between the two groups were compared. The relationships between ALFF values and clinical measurements were analysed using a multiple-factor analysis. Compared to the controls, the DR group showed significantly increased ALFF values in the bilateral occipital gyrus, right lingual gyrus, and precuneus, and decreased values in the right posterior/anterior cerebellar lobe and the parahippocampal, fusiform, superior temporal, inferior parietal, and angular gyrus. Furthermore, the Montreal Cognitive Assessment (MoCA) scores were negatively correlated with decreased ALFF values in the right occipital lobe of the DR group, while increased ALFF values in the right precuneus and lingual gyrus were found to be positively correlated with glycosylated haemoglobin (HbA1c) levels. Patients with DR showed spontaneous cerebral activity abnormalities in many cerebral regions that were associated with cognitive impairments. HbA1c levels altered spontaneous cerebral activity in DR patients.


Reversibility of the effect of tacrine on the secretion of the beta-amyloid precursor protein in cultured cells.
The amyloid beta-protein (A beta) of Alzheimer's disease is derived from a family of large integral membrane glycoproteins, beta-amyloid precursor proteins (beta APP). Two secretory proteolytic pathways are involved in the metabolism of beta APP. The major pathway involves cleavage within the A beta sequence and generates carboxyl-truncated derivatives of beta APP which are secreted into the conditioned medium of cells. The minor 'amyloidogenic' pathway results in the production of A beta. Here, cell cultures were used to examine the metabolism of beta APP by tacrine, a centrally active cholinesterase inhibitor reported to improve cognitive deficits. Treatment with tacrine in cells resulted in the drastic inhibition of secretion of the major isoforms of beta APP into the medium. The effect of tacrine can be reversed by washing away the drug from the cells. Treatment with tacrine did not change the level of either HSP-70 or LDH. Thus, the inhibitory effect of tacrine on the secretion of beta APP was not due to the permanent damage or loss of cells as normal release of beta APP could be restored when the drug was washed away.


In vitro inhibition of human cytomegalovirus replication in human foreskin fibroblasts and endothelial cells by ascorbic acid 2-phosphate.
Antiviral activity of L-ascorbic acid-2-phosphate (ASC-2P), a long-acting derivative of L-ascorbic acid, against several human cytomegalovirus (CMV) strains was examined in cultures of human foreskin fibroblasts (HFF) and endothelial cells (EC). ASC-2P at concentrations ranging from 0.2 to 2 mM had no effect on the number of cells expressing 72 kDa CMV immediate early antigen (IEA) while it inhibited expression of 68 kDa late antigen (LA) in infected cultures of both cell types (30% and 55% reduction for EC and HFF, respectively). In HFF cells, virus yield was reduced up to 4-fold, when ASC-2P was added after CMV infection. Antiviral effects were significantly increased in cultures pretreated with ASC-2P. In HFF and EC pretreated for three subcultures (18 days) with 0.2 mM ASC-2P, a significant reduction of cells expressing IEA (75% and 80% reduction in EC and HFF, respectively) and LA (92% and 90% reduction for EC and HFF, respectively) was observed. Pretreatment for three subcultures with ASC-2P inhibited virus yield 50- to 100-fold in EC and 100- to 1000-fold in HFF. The continuous presence of ASC-2P was not required for its antiviral activity. A significantly higher reduction of virus replication with ganciclovir and foscarnet was obtained in ASC-2P pretreated cells than in untreated controls. The results showed that ASC-2P provides L-ascorbic acid with long-lasting antiviral activity against CMV. ASC-2P may be of benefit for the adjunctive treatment of CMV infection.


A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial.
We sought to determine whether the substantial benefits of topical nitroglycerin with first-line, platinum-based, doublet chemotherapy in advanced nonsmall-cell lung cancer (NSCLC) seen in a phase II trial could be corroborated in a rigorous, multicenter, phase III trial. Patients starting one of five, prespecified, platinum-based doublets as first-line chemotherapy for advanced NSCLC were randomly allocated treatment with or without nitroglycerin 25 mg patches for 2 days before, the day of, and 2 days after, each chemotherapy infusion. Progression-free survival (PFS) was the primary end point. Accrual was stopped after the first interim analysis of 270 events. Chemotherapy was predominantly with carboplatin and gemcitabine (79%) or carboplatin and paclitaxel (18%). The final analysis included 345 events in 372 participants with a median follow-up of 33 months. Topical nitroglycerin had no demonstrable effect on PFS [median 5.0 versus 4.8 months, hazard ratio (HR) = 1.07, 95% confidence interval (CI) 0.86-1.32, P = 0.55], overall survival (median 11.0 versus 10.3 months, HR = 0.99, 95% CI 0.79-1.24, P = 0.94), or objective tumor response (31% versus 30%, relative risk = 1.03, 95% CI 0.82-1.29, P = 0.81). Headache, hypotension, syncope, diarrhea, dizziness, and anorexia were more frequent in those allocated nitroglycerin. The addition of topical nitroglycerin to carboplatin-based, doublet chemotherapy in NSCLC had no demonstrable benefit and should not be used or pursued further. Australian New Zealand Clinical Trials Registry Number ACTRN12608000588392.


Complexes of acridine and 9-chloroacridine with I2: formation of unusual I6 chains through charge-transfer interactions involving amphoteric I2.
Acridine and 9-chloroacridine form charge-transfer complexes with iodine in which the nitrogen-bound I2 molecule is amphoteric; one end serves as a Lewis acid to the heterocyclic donor, while the other end acts as a Lewis base to a second I2 molecule that bridges two acridine.I2 units. In the acridine derivative [(acridine.I2)2.I2, 1], the dimer has a "zigzag" conformation, while in the 9-chloroacridine derivative [(9-Cl-acridine.I2)2.I2, 2], the dimer is "C-shaped". The thermal decomposition of the two complexes is very different. Compound 1 loses one molecule of I2 to form an acridine.I2 intermediate, which has not been isolated. Further decomposition gives acridine as the form II polymorph, exclusively. Decomposition of 2 involves the loss of two molecules of I2 to form a relatively stable intermediate [(9-Cl-acridine)2.I2, 3]. Compound 3 consists of two 9-Cl-acridine molecules bridged through N...I charge-transfer interactions by a single I2 molecule. This compound represents the first known example, in which both ends of an I2 molecule form interactions in a complex that is not stabilized by the extended interactions of an infinite chain structure. The ability of the terminal iodine of an N-bound I2 to act either as an electron donor (complexes 1 and 2) or as an electron acceptor (complex 3) can be understood through a quantum mechanical analysis of the systems. Both electrostatic interactions and the overlap of frontier molecular orbitals contribute to the observed behavior.


Assessing arterial inflow before infra-inguinal bypass grafting: a survey of the members of the Vascular Surgical Society of Great Britain and Ireland.
The optimal assessment of arterial inflow is controversial. We investigated current preferences of inflow assessment prior to infra-inguinal bypass grafting. A questionnaire was sent to 364 members of the Vascular Surgical Society of Great Britain and Ireland asking about inflow assessment in different clinical situations, access to resources, size of hospital and number of grafts performed each year. Questionnaires analysed = 169. Angiography was used by 89.5%, most single view. Two views angiography was used more often by surgeons performing more than 20 femoro-distal grafts each year (79.3 versus 37.6%). Routine use of iliac duplex was < 20%; poor femoral pulse increased this to near 30%. About 90% of respondents had access to colour flow duplex. Most respondents use single-plane angiography to assess inflow before infra-inguinal grafting. Two views and functional tests are used more commonly by surgeons working in larger or teaching hospitals and those performing more grafts.


Structure of alpha-glycerophosphate oxidase from Streptococcus sp.: a template for the mitochondrial alpha-glycerophosphate dehydrogenase.
The FAD-dependent alpha-glycerophosphate oxidase (GlpO) from Enterococcus casseliflavus and Streptococcus sp. was originally studied as a soluble flavoprotein oxidase; surprisingly, the GlpO sequence is 30-43% identical to those of the alpha-glycerophosphate dehydrogenases (GlpDs) from mitochondrial and bacterial sources. The structure of a deletion mutant of Streptococcus sp. GlpO (GlpODelta, lacking a 50-residue insert that includes a flexible surface region) has been determined using multiwavelength anomalous dispersion data and refined at 2.3 A resolution. Using the GlpODelta structure as a search model, we have also determined the intact GlpO structure, as refined at 2.4 A resolution. The first two domains of the GlpO fold are most closely related to those of the flavoprotein glycine oxidase, where they function in FAD binding and substrate binding, respectively; the GlpO C-terminal domain consists of two helix bundles and is not closely related to any known structure. The flexible surface region in intact GlpO corresponds to a segment of missing electron density that links the substrate-binding domain to a betabetaalpha element of the FAD-binding domain. In accordance with earlier biochemical studies (stabilizations of the covalent FAD-N5-sulfite adduct and p-quinonoid form of 8-mercapto-FAD), Ile430-N, Thr431-N, and Thr431-OG are hydrogen bonded to FAD-O2alpha in GlpODelta, stabilizing the negative charge in these two modified flavins and facilitating transfer of a hydride to FAD-N5 (from Glp) as well. Active-site overlays with the glycine oxidase-N-acetylglycine and d-amino acid oxidase-d-alanine complexes demonstrate that Arg346 of GlpODelta is structurally equivalent to Arg302 and Arg285, respectively; in both cases, these residues interact directly with the amino acid substrate or inhibitor carboxylate. The structural and functional divergence between GlpO and the bacterial and mitochondrial GlpDs is also discussed.


Dental anxiety and psychological functioning in children: its relationship with behaviour during treatment.
In this study the relationship between the levels of dental anxiety, psychological functioning and earlier experience with dental injections are examined and the possible influence of these factors on children's behaviour before and during a local anaesthesia injection. A total of 128 children (4-11 years) were included. The level of dental anxiety and the psychological functioning were measured using the 'Children's Fear Survey Schedule' (CFSS-DS) and the 'Strengths and Difficulties Questionnaire' (SDQ). Based on video recordings the anxiety behaviour was scored on the Venham-scale. There was a positive correlation between levels of dental anxiety, psychological functioning and anxiety behaviour before and during the dental injection. In particular children with emotional problems or peer problems tended to show more anxiety behaviour before the injection and children with emotional or hyperactivity problems tend to show more anxiety behaviour during the injection. Furthermore, the younger children (below 6 years of age), with previous dental experience in the past 6 months, tended to display more anxiety behaviour both before and during the injection than children without or with experience from longer ago. The level of dental anxiety and psychological functioning and recent previous dental experience are important factors in determining which child is likely to display more anxiety and uncooperative behaviour during treatment and therefore potentially need more attention to be able to cope well with dental treatment.


Primary cervical neuroblastoma in infants.
Although neuroblastoma is a relatively common malignancy of childhood, it is rarely of cervical origin. We encountered two cases of primary cervical neuroblastoma in infants. The first case was in a newborn who presented with noisy breathing, dyspnea, and choking on feeding soon after birth. Physical examination disclosed a left retropharyngeal mass near the midline causing aerodigestive compromise. Magnetic resonance imaging showed a well-defined hyperintense mass in the corresponding region. The infant underwent complete surgical excision of the mass 1 month after birth. The pathology report confirmed neuroblastoma. Horner's syndrome developed soon after surgery but resolved spontaneously within 6 months. No recurrence was noted during a 3-year follow-up period. The second patient, a 5-month-old female, presented with stridor and shortness of breath of 2-weeks' duration due to a right cervical mass. Magnetic resonance imaging showed a parapharyngeal mass suggestive of neuroblastoma. Complete surgical excision was done at the expense of sacrificing the sympathetic nerve trunk. The pathologic diagnosis was moderately differentiated neuroblastoma. No recurrence was noted when the patient was seen 2 years after surgery, although right-sided Horner's syndrome persisted. Surgical intervention can result in a good prognosis for low stage cervical neuroblastomas; however, long-term follow-up is important.


Thoracic splenosis.
Thoracic splenosis is a rare pathologic entity resulting from seeding of splenic tissue in the pleural cavity after thoracoabdominal trauma. A 45-year-old man with a history of splenectomy secondary to abdominal trauma presented with a left lung mass and an inconclusive tissue diagnosis after needle biopsy. Thoracic splenosis was not suspected preoperatively, considered on an intraoperative frozen section, and established on permanent pathologic biopsy specimens obtained during thoracotomy. A history of thoracoabdominal trauma, combined with radiologic and radionuclide imaging studies, may establish the diagnosis without thoracotomy.


The Sarmiento tibial plaster: a prospective study of 145 fractures.
A prospective series of 145 fractures of the tibia was treated with the Sarmiento below-knee functional cast between 1973 and 1979. In only 3 patients was it not possible to use the cast for reasons connected with the method. The cast was applied in 88 per cent of cases within 4 weeks of injury. Control of angulatory deformity and shortening was satisfactory and the results approach those reported by Sarmiento. The results regarding the speed of healing also stand comparison with Sarmiento's but difficulties inherent in the interpretation of these results are discussed. The PTB cast has been found to be an effective and safe method for the treatment of tibial shaft fractures.


Predicting the likely response of data-poor ecosystems to climate change using space-for-time substitution across domains.
Predicting ecological response to climate change is often limited by a lack of relevant local data from which directly applicable mechanistic models can be developed. This limits predictions to qualitative assessments or simplistic rules of thumb in data-poor regions, making management of the relevant systems difficult. We demonstrate a method for developing quantitative predictions of ecological response in data-poor ecosystems based on a space-for-time substitution, using distant, well-studied systems across an inherent climatic gradient to predict ecological response. Changes in biophysical data across the spatial gradient are used to generate quantitative hypotheses of temporal ecological responses that are then tested in a target region. Transferability of predictions among distant locations, the novel outcome of this method, is demonstrated via simple quantitative relationships that identify direct and indirect impacts of climate change on physical, chemical and ecological variables using commonly available data sources. Based on a limited subset of data, these relationships were demonstrably plausible in similar yet distant (>2000 km) ecosystems. Quantitative forecasts of ecological change based on climate-ecosystem relationships from distant regions provides a basis for research planning and informed management decisions, especially in the many ecosystems for which there are few data. This application of gradient studies across domains - to investigate ecological response to climate change - allows for the quantification of effects on potentially numerous, interacting and complex ecosystem components and how they may vary, especially over long time periods (e.g. decades). These quantitative and integrated long-term predictions will be of significant value to natural resource practitioners attempting to manage data-poor ecosystems to prevent or limit the loss of ecological value. The method is likely to be applicable to many ecosystem types, providing a robust scientific basis for estimating likely impacts of future climate change in ecosystems where no such method currently exists.


Chronic treatment with clozapine or haloperidol differentially regulates dopamine and serotonin receptors in rat brain.
Long-term administration of the atypical neuroleptic clozapine (CLZ) poses a much lower risk of extrapyramidal side effects (EPS) than does the use of typical neuroleptics such as haloperidol (HAL). To investigate the neural mechanisms of the differing CNS activities of these two drugs, we used quantitative autoradiography to measure changes in dopamine and serotonin receptors in rats after injection with CLZ or HAL for 21 days at clinically relevant dose ratios. Levels of D1, D2, and 5-HT2 receptors were determined in frontal cortex, caudate-putamen, and nucleus accumbens. Rats that received CLZ chronically showed CNS receptor changes markedly different from those in chronic HAL-treated animals. Whereas rats treated chronically with HAL showed enhanced striatal D2 binding (average increase of 42%), those treated with CLZ did not. In contrast, chronic CLZ, but not chronic HAL, induced enhanced striatal D1 binding (average increase of 43%). Finally, CLZ treatment decreased 5-HT2 receptor binding by an average of 37%, while HAL had no significant effect. The effects of chronic HAL or CLZ treatment on receptors were similar in all forebrain areas examined. However, since D1 and 5-HT2 receptors are more abundant than D2 sites in limbic and neocortical areas, the preferential modulation of D1 and 5-HT2 receptors by CLZ suggests a greater impact of this atypical neuroleptic on activity of the limbic system than that achieved by the typical neuroleptic, HAL. These findings suggest that the clinical profile of atypical neuroleptics such as CLZ may be attributed to their effects on a receptor profile differing in pharmacological characteristics and anatomical distribution from that affected by typical neuroleptics.


DNA copy gains of tumor-related genes in vestibular schwannoma.
DNA copy gains are a common event in tumor growth. This study determines the gene dosage/amplification of seven tumor-related genes in patients undergoing vestibular schwannoma (VS) surgery and analyzes its clinical implications. Thirty-three patients undergoing surgery for VS were studied. Seven genes (EGFR, ERBB2, ERBB3, ERBB4, MDM2, MDM4, and NMYC) were analyzed by Quantitative real-time PCR. Copy gains were correlated with demographic, clinical and radiological data. Of the 33 samples, 48 % were positive for copy gains in at least one gene. There were no positive samples for gene amplification. A clinical correlation between tumor size and copy gains of ERBB2 was found. Patients with copy gains of this gene had larger tumors measured by diameter (p = 0.027) and volume (p = 0.005). Copy gains of EGFR, ERBB2, ERBB4, and MDM4 were associated with preoperative tinnitus. Contrary to other tumors of the central nervous system, development of VS does not appear to involve gene amplification. However, copy gains of certain tumor-related genes may play a role in the biological behavior of these neoplasms. Our findings support the role of ERBB2 in VS development and growth.


Effectiveness of instruction and video feedback on staff's trainer behavior during one-to-one training with children with severe intellectual disabilities.
In this study, the effectiveness of instruction and video feedback on response prompting and trainer behavior of direct-care staff during one-to-one training with five children with severe intellectual disability was assessed. During instruction, written information and verbal instruction were given concerning correct and incorrect trainer behavior and response prompting. Video feedback consisted of (a) interrupting a video presentation if an error occurred, (b) providing positive feedback, and (c) prompting the trainer to avoid errors or omissions. The results showed that instruction resulted in an improvement (though not significantly) in correct trainer behavior while video feedback was significantly effective in improving correct trainer behavior. Results were maintained at a 5-week follow-up.


Transition index maps for urban growth simulation: application of artificial neural networks, weight of evidence and fuzzy multi-criteria evaluation.
Transition index maps (TIMs) are key products in urban growth simulation models. However, their operationalization is still conflicting. Our aim was to compare the prediction accuracy of three TIM-based spatially explicit land cover change (LCC) models in the mega city of Mumbai, India. These LCC models include two data-driven approaches, namely artificial neural networks (ANNs) and weight of evidence (WOE), and one knowledge-based approach which integrates an analytical hierarchical process with fuzzy membership functions (FAHP). Using the relative operating characteristics (ROC), the performance of these three LCC models were evaluated. The results showed 85%, 75%, and 73% accuracy for the ANN, FAHP, and WOE. The ANN was clearly superior compared to the other LCC models when simulating urban growth for the year 2010; hence, ANN was used to predict urban growth for 2020 and 2030. Projected urban growth maps were assessed using statistical measures, including figure of merit, average spatial distance deviation, producer accuracy, and overall accuracy. Based on our findings, we recomend ANNs as an and accurate method for simulating future patterns of urban growth.


Enhanced Exciplex Emission of Pyrene Thin Films Doped by Perylene: Structural, Photophysical and Morphological Investigation.
The present work reports on the preparation of thin films of pyrene luminophors doped by varying amounts of perylene by spin coating technique. The structural, morphological, and photophysical properties of pyrene thin films have been investigated as a function of perylene contents. X-ray diffraction studies of doped thin films show well-defined peaks, and estimated crystallite size decreases with increasing perylene content, due to the formation of closed packed crystal structure. SEM images of pure pyrene revealed smooth, and compact and separated crystals with amounts of perylene. The result of absorption spectra showed decrease in intensity with perylene content. However, the fluorescence spectra of pyrene containing higher amounts of perylene showed broad and structureless exciplex emission at 510 nm. The emission colour of pyrene luminophors tuned from blue to green by controlling the concentration of perylene. The phenomenon of change in colour was seen due to efficient excitation energy transfer from pyrene to perylene in thin films. It also found that the intensity of exciplex emission increases with increasing concentration of perylene is of high demand in fluorescent lamp as well as green organic light emitting diodes.


Project profile: a multicenter study on breast cancer in young women in Latin America (PRECAMA study).
To describe the rationale and the methodology of a multicenter project to study the etiology of breast cancer in young Latin American women. The International Agency for Research on Cancer has established an international collaborative population-based case-control study in four countries in Latin America: Chile, Colombia, Costa Rica, and Mexico (the PRECAMA study). Standardized methodologies were developed to collect information on reproductive variables, lifestyle, anthropometry, diet, clinical and pathological data, and biological specimens. The study will be extended to other countries in the region. PRECAMA is unique in its multidisciplinary approach that combines genetics, genomics, and metabolomics with lifestyle factors. Then data generated through this project will be instrumental to identify major risk factors for molecular subtypes of breast cancer in young women, which will be important for pre- vention and targeted screening programs in Latin America.


[Diagnostic imaging of bone metastases].
To present an "algorithm" for detection and diagnosis of skeletal metastases, which may be applied differently in symptomatic and asymptomatic cancer patients. February to March 1999 we randomly selected and retrospectively reviewed the clinical charts of 100 cancer patients (70 women and 30 men; mean age: 63 years, range: 55-87). All the patients had been staged according to TNM criteria and had undergone conventional radiography and bone scan; when findings were equivocal, CT and MRI had been performed too. The primary lesions responsible for bone metastases were sited in the: breast (51 cases), colon (30 cases: 17 men and 13 women), lung (7 cases: 6 men and 1 woman), stomach (4 cases: 2 men and 2 women), skin (4 cases: 3 men and 1 woman), kidney (2 men), pleura (1 woman), and finally liver (1 men). The most frequent radiographic pattern was the lytic type (52%), followed by osteosclerotic, mixed, lytic vs. mixed and osteosclerotic vs lytic patterns. The patients were divided into two groups: group A patients were asymptomatic and group B patients had local symptoms and/or pain. Skeletal metastases are the most common malignant bone tumors: the spine and the pelvis are the most frequent sites of metastasis, because of the presence of high amounts of red (hematopoietic active) bone marrow. Pain is the main symptom, even though many bone metastases are asymptomatic. Pathological fractures are the most severe consequences. With the algorithm for detection and diagnosis of skeletal metastases two different diagnostic courses are available for asymptomatic and symptomatic patients. Bone scintigraphy remains the technique of choice in asymptomatic patients in whom skeletal metastases are suspected. However this technique, though very sensitive, is poorly specific, and thus a negative bone scan finding is double-checked with another physical examination: if the findings remain negative, the diagnostic workup is over. On the contrary, in patients with a positive bone scan or with local symptoms and pain, radiography and CT are used for screening of metastatic lesions: results may be negative (for low sensitivity of conventional radiology) or questionable (in which case bone biopsy is necessary), or else symptoms may be due to different causes than metastatic lesions (i.e., osteoarthritis). Before bone biopsy is made, MRI must be performed, because it is the only technique that allows to distinguish between bone marrow components. The limitation of MRI is the poor specificity of its findings, which may provide misleading findings.


Temporal resolution in olfaction: stimulus integration time of lobster chemoreceptor cells
The stimulus integration time of lobster olfactory receptor cells in situ was determined using extracellularly recorded spiking responses from receptor cells and on-line high-resolution measurement of odor square pulses. At a fixed odor concentration, odor steps of 200 ms duration elicited maximum responses; shorter odor steps did not drive the cells to their maximum response and longer odor steps added spikes but did not result in higher firing rates. Excitatory processes peaked within 220 ms of stimulus onset. At 160300 ms, stimulus intensity discrimination was most evident. Adaptation processes reduced response magnitude to near-zero levels within 1000 ms of stimulus onset. Olfactory receptor cells thus resolve odor peak onsets within the first few hundred milliseconds: this time window corresponds to the 45 Hz frequency of olfactory sampling (i.e. 'sniffing') as well as the rapid fluctuations in odor concentration that are common in natural odor plumes. The stimulus integration time of 200 ms may play a role in the filtering of information used by lobsters to orient to distant odor sources.


Evaluation of endovascular therapy combined with bowel resection treatment on patients with Acute Mesenteric Venous Thrombosis.
This retrospective study aims to investigate the effects of the endovascular and surgical strategy for treating patients with Acute Mesenteric Venous Thrombosis (AMVT). We retrospectively studied 68 patients with AMVT who underwent treatment in Jinling Hospital during the period from January 2009 to December 2014. The mean age was 45 ± 12 years (range 20 to 72 years). All patients were treated by using the combined treatment that included endovascular treatment, damage control surgery, surgical intensive care, and intestinal rehabilitation treatment. Clinical outcomes and complications were compared during the follow-up period. All the 68 cases received anticoagulant treatment. However, only 24 received the endovascular intervention, 19 received surgical resection, and 25 patients received endovascular treatment combined with bowel resection. The overall mortality rate was 2.94% (2 cases). Bowel resection range significantly decreased（92±14cm vs. 162±27cm, t=-2.377, P= 0.022）in the combination therapy group, when compared with the surgery group. During the 1-year follow-up period, 4 cases suffered from short bowel syndrome. Our study indicates that AMVT can be successfully treated with the early improvement of intestinal blood circulation. Further, our applied combined approach showed a favorable outcome in mesenteric thrombosis patients and reduced the mortality rate by improving the prognosis significantly.


[Cycloaddition of 1-methyl-2(1H)-quinolones having an electron-withdrawing group at the 3 or 4-position with 1,3-butadiene derivatives].
Cycloaddition of 1-methyl-2(1H)-quinolones with electron-withdrawing groups such as methoxycarbonyl, cyano, and acetyl groups, at the 3 or 4-position with 2,3-dimethoxy- and 2-(trimethylsilyloxy)-1,3-butadienes afforded stereoselectively phenanthridone derivatives under atmospheric and high pressures. Furthermore, regioselectivities of the cycloaddition of 3- or 4-substituted 2 (1H)-quinolones with 2-(trimethylsilyloxy)-1,3-butadiene were examined using MO calculation.


Pre-conditioning and postconditioning to limit ischemia-reperfusion-induced myocardial injury: what could be the next footstep?
Myocardial ischemia is a condition in which the coronary blood flow to the heart is reduced, which results in deficient oxygen and nutrients supply to the heart. Reperfusion to an ischemic myocardium often results in lethal myocardial injury. The brief episodes of ischemia and reperfusion given before prolonged ischemia and reperfusion denote pre-conditioning. On the other hand, brief episodes of ischemia and reperfusion given after prolonged ischemia and at the onset of reperfusion denotes postconditioning. Pre- and postconditioning are anti-jeopardized phenomenons in which both forms have been shown to protect the myocardium from lethal ischemia-reperfusion injury. However, numerous experimental studies reveal that the cardioprotective effects of these phenomenons have been suppressed in presence of some pathological factors such as hyperglycemia, obesity, hypercholesterolemia, etc. In this review, we have critically discussed the mechanisms involved in the cardioprotective effects of pre- and postconditioning to limit ischemia-reperfusion-induced myocardial injury. Moreover, the clinical relevance and factors affecting the cardioprotective potentials of pre- and postconditioning have been delineated.


Quantitative polymerase chain reaction analysis of mdr1 mRNA in multiple myeloma cell lines and clinical specimens.
We have designed a new polymerase chain reaction (PCR) protocol for the quantitation of mdr1 mRNA in cell lines and clinical specimens. This protocol uses an in vitro-generated RNA molecule as an internal standard. This synthetic RNA contains the same mdr1 primer sequences as the cellular mRNA, but yields a different-sized PCR product after amplification. Since a single primer set is used in quantitation, differences in primer efficiency are not a concern. We have used this assay to measure mdr1 expression in a multiple myeloma cell line, 8226/S, its drug resistant variants 8226/dox6 and 8226/dox40, and tumor samples from 10 patients with B-cell malignancies (9 multiple myeloma, 1 chronic lymphocytic leukemia). 8226/S does not express mdr1 mRNA. 8226/dox6 is 10-fold resistant to doxorubicin, and expresses 32 mdr1 mRNA/10 pg cellular RNA. 8226/dox40 is 140-fold resistant to doxorubicin, and expresses 890 mdr1 mRNA/10 pg cellular RNA. Seven of the 10 patients had levels of mdr1 mRNA expression below that seen in the multidrug-resistant, human multiple myeloma cell line, 8226/dox6. Three patients had levels of mdr1 expression comparable to those seen in 8226/dox6. No patient had levels of mdr1 expression close to that seen in 8226/dox40. Sample RNA integrity is assured by PCR analysis of a different, ubiquitous, cell cycle independent, histone variant, H3.3. This assay will be useful for studying low level mdr1 expression in cell lines and clinical specimens.


Phonological awareness and literacy development in children with expressive phonological impairments.
This study investigated the link between expressive phonological impairments, phonological awareness, and literacy. Previous investigations of literacy skills in children with speech impairments have given mixed results; here we considered whether presence of additional language impairments or severity of the speech impairment was an important prognostic factor. Thirty-one children with expressive phonological impairments were compared with control children matched on age and nonverbal ability on three occasions, at mean ages of 70, 79, and 91 months. On each occasion they were given three tests of phonological awareness: one involved rime-matching and two involved onset-matching. At assessments 2 and 3 literacy skills were assessed. Children with phonological impairments scored well below their controls on phonological awareness and literacy, independent of whether or not they had other language problems. Although many of them knew letter sounds, they were poor at reading and writing nonwords as well as real words. It is suggested that both the speech impairment and the literacy problems arise from a failure to analyze syllables into smaller phonological units. The severity of the phonological problems in relation to age is an important determinant of literacy outcome; children who have severe expressive phonological impairments at the time they start school are at particular risk for reading and spelling problems.


[Complete androgen insensitivity syndrome: a novel mutation in a Tunisian family].
Complete androgen insensitivity is a rare syndrome. It is caused by a mutation in the androgen receptor gene. We describe a novel mutation in exon 1. We report the case of a 29 year-old girl with complete androgen insensitivity syndrome discovered during the exploration of a primary amenorrhoea. The family investigation revealed two other cases. The diagnosis was oriented by the clinical and the biological features and confirmed by the molecular study. A new mutation of the androgen receptor gene, as a deletion in exon 1 not described previously, was identified. Through these cases, clinical, hormonal and histological particularities were analysed.


Late-fluorescence mammography assesses tumor capillary permeability and differentiates malignant from benign lesions.
Using scanning time-domain instrumentation we recorded fluorescence projection mammograms on few breast cancer patients prior, during and after infusion of indocyanine green (ICG), while monitoring arterial ICG concentration by transcutaneous pulse densitometry. Late-fluorescence mammograms recorded after ICG had been largely cleared from the blood by the liver, showed invasive carcinomas at high contrast over a rather homogeneous background, whereas benign lesions did not produce (focused) fluorescence contrast. During infusion, tissue concentration contrast and hence fluorescence contrast is determined by intravascular contributions, whereas late-fluorescence mammograms are dominated by contributions from protein-bound ICG extravasated into the interstitium, reflecting relative microvascular permeabilities of carcinomas and normal breast tissue. We simulated intravascular and extravascular contributions to ICG tissue concentration contrast within a two-compartment unidirectional pharmacokinetic model.


Choline head groups stabilize the matrix loop regions of the ATP/ADP carrier ScAAC2.
ATP/ADP carriers (AACs) are essential to the cell as they exchange ATP produced in mitochondria for cytosolic ADP. Monoclonal antibodies against the isoform 2 of Saccharomyces cerevisiae AAC (ScAAC2) were used to probe the accessibility of the matrix loops 1 and 3 depending on the environment of the carrier. In mitochondrial membranes ScAAC2 was not recognized, whereas in dodecylmaltoside the antibodies bound to the carrier, suggesting that the epitopes are hidden in the native environment. Exposure of the epitopes by detergents was reversed by reconstitution of the carrier in phospholipids or by exchanging with detergents having a choline or a trimethylammonium head group. Circular dichroism spectroscopy on peptides representing the C-terminal regions of all three matrix loops showed that only phosphocholine detergents induced a structural reorganization. Since in addition phosphatidylcholine was found to be tightly associated with the purified carrier, the matrix loop regions are likely to be associated to the membrane by phosphatidylcholine.


Inhibition of interleukin 3 and granulocyte-macrophage colony-stimulating factor stimulated increase of active ras.GTP by herbimycin A, a specific inhibitor of tyrosine kinases.
Interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate the proliferation of several kinds of cultured hematopoietic cell lines. Growth signals from IL-3 and GM-CSF cause accumulation of active Ras.GTP complexes in PT18 mouse mast cell line (Satoh, T., Nakafuku, M., Miyajima, A., and Kaziro, Y. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 3314-3318). In this paper we describe the effect of herbimycin A, a tyrosine kinase-specific inhibitor, on the activation of Ras. The increase of Ras.GTP induced by IL-3 and GM-CSF diminished in cells treated with 0.5 approximately 1 micrograms/ml of herbimycin A for 24 h prior to the addition of the growth factors. Under this condition, the extent of phosphorylation on tyrosine residues of proteins decreased. However, the activity of cAMP-dependent protein kinase and protein kinase C did not change. Growth of cells in the presence of IL-3 or GM-CSF was also completely inhibited. These observations suggest that tyrosine kinases are involved in the pathways between IL-3 and GM-CSF receptors and Ras and that they are essential for the growth stimulated by these growth factors.


Acrylamide exposure preferentially impairs axonal transport of glycoproteins in myelinated axons.
The right L5 dorsal root ganglion of adult rats exposed to acrylamide (40 mg/kg body weight/day for nine consecutive days) was injected with either [3H]methionine or [3H]glucosamine. After allowing incorporation into macromolecules and axonal transport to proceed for 5 hr, the distribution of radioactivity in cross sections and longitudinal sections of sciatic nerve was determined by autoradiography. Control and treated animals showed no difference in distribution of label within the sciatic nerve with respect to rapidly transported proteins labelled with [3H]methionine. In control animals the distribution of rapidly transported glycoproteins labelled with [3H]glucosamine was similar to that found for [3H]methionine-labelled proteins. In contrast, acrylamide-exposed rats had a very different distribution of labelled glycoproteins; there was a marked paucity of label in the myelinated axons. We interpret this result as indicating that acrylamide preferentially inhibits glycosylation or axonal transport of glycoproteins in neurons bearing myelinated axons.


Experimental effects of acute exercise duration and exercise recovery on mood state.
Accumulating evidence suggests that, in addition to various psychosocial parameters, affective responses to exercise play an important role in subserving future exercise behavior. This study comprehensively evaluated whether acute exercise duration and recovery period influenced the relationship between moderate-intensity walking exercise and mood profile. We employed a randomized controlled cross-over trial. Participants completed two laboratory visits, separated by one-week. One of the visits involved a mood profile assessment with no exercise, while the other visit involved a mood profile assessment after an acute bout of exercise. Participants (N = 352; 22 per group; young [Mage = 21 yrs] healthy adults) were randomized into one of 16 experimental groups: 10, 20, 30, 45 or 60min bout of exercise coupled with either a 5, 15 or 30min recovery period. The exercise bout was of moderate-intensity (40-59% of HRR). Mood profile was assessed from the POMS survey, considering subscales of depression, anger and hostility. For all three mood profile parameters, there was no evidence of a group x time interaction effect. However, the main effect for time was statistically significant for each mood parameter. These significant results demonstrate that, generally, exercise had a favorable effect on each of the mood profile, regardless of exercise duration and recovery period. In addition to the significant main effects for time, we also observed a significant main effect for group for the mood parameter hostility. With the exception of the group 13 (60min of exercise with 5min recovery) and the 3 groups that employed a 10-min bout of exercise (groups 1-3), all other experimental groups had a lower (better) hostility score after the exercise visit. Generally, exercise had a favorable effect on various mood profiles, regardless of exercise duration (between 10 and 60min) and recovery period (between 5 and 30min).


The engineering, structure, and DNA binding properties of a novel His4-type zinc finger peptide.
We have created a novel His4-type zinc finger protein (H4Sp1) engineered by Cys-->His mutations of the Cys2His2-type zinc finger in transcription factor Sp1. The CD and NMR studies reveal that the His4 domain has Zn(II)-dependent folding properties and similar secondary structures to wild-type Cys2His2 domain. The DNA binding experiments demonstrate that H4Sp1 can bind DNA in a specific way. The present artificial peptide H4Sp1 will provide valuable information about the interaction between a metallopeptide and DNA.


Response of lipoprotein lipase to calorie intake in streptozotocin-induced diabetic rats.
The mechanism regulating lipoprotein lipase (LPL) expression in adipose tissue was examined in rats in the conditions of different calorie intakes with and without streptozotocin-induced (STZ-) diabetes. The LPL activity released from adipose tissue was greater with the higher calorie intake (20 g of normal chow diet per day) than with the lower calorie intake (13 g of normal chow diet per day), and was greater in normal rats than in STZ-diabetic rats. The LPL activity was proportional to the serum insulin level in all conditions. Dot-blot analysis showed that the amount of LPL mRNA in adipose tissue was increased by the higher calorie diet and that the increase was less in the diabetic state. Expression of mRNA was also nearly parallel with the serum insulin level. LPL activity released from the heart was not affected by either the calorie intake or the diabetic state. These results suggest that the mechanisms of LPL expression in adipose tissue and the heart are different, and that LPL expression in adipose tissue was closely dependent on the insulin level.


[The importance, indication and operative technique of dorsal synovectomy of the knee joint in rheumatic diseases (author's transl)].
From a logical basis, it is reasonable to postulate that a synovectomy must be maximally as complete as possible. The indications and operative technique of radical synovectomy of the dorsal part of the knee joint are presented. The statistically significant improvement of the results of knee synovectomy by an additional dorsal approach is referred to.


Upconversion Nanoparticle-Based Strategy for Crossing the Blood-Brain Barrier to Treat the Central Nervous System Disease.
The blood-brain barrier (BBB) is a major challenge for the treatment of central nervous system (CNS) diseases. The BBB strictly regulates the movement of molecules into and out of the brain, and therefore protects the brain from noxious agents. However, for this reason the BBB also acts as a major obstacle that prevents most therapeutic molecules from getting into the target site of the brain. Therefore, it is essential to develop an efficient and general approach to overcome the BBB and transport the drug to the targeted region. Nanoparticle-based drug delivery systems are emerging as a promising drug delivery platform, due to their distinct advantages of tunable biophysical properties such as surface chemistry, size, and shape leading to various biological actions (like clearance, biodistribution, and biocompatibility) in the body. Therefore, it was hypothesized that the surface and shape of nanoparticles will influence their BBB permeation efficiency. Here, we describe a series of upconversion nanoparticles with different surfaces (oleic acid-free, DNA-modified, Silica coating, and PEG-encapsulated), PEGylated UCNPs with various shapes were generated (including sphere and rod). The cellular uptake ability, biodistribution, and BBB penetration of those UCNPs were assessed in cultured cells (NSC-34 neuron- like cells) and in vivo (zebrafish models).


Skin graft secured by VAC (vacuum-assisted closure) therapy in chronic leg ulcers: A controlled randomized study.
Leg ulcers are a common condition. There have been very few studies of combined therapy involving VAC (vacuum-assisted closure) and skin graft. We performed a randomized controlled trial of VAC therapy vs. hydrocolloid dressings over 5 days following autologous grafting on chronic leg ulcers. The primary objective was to assess the difference in success (defined as a reduction in wound area of at least 50% at 1 month) between the two dressing methods. Forty-six patients with ulcers present for over one month were included. Following a 7-day hospitalization period, follow-up was performed for 3 months on an outpatient basis. Our study does not demonstrate a statistically significant difference, with a 45.8% success rate in the VAC group vs. 40.9% in the conventional dressing group (P=0.73). In the venous ulcer group, the success rate was 57.9% for VAC vs. 40% for conventional dressings (P=0.3). The difference in favor of VAC in this group was not statistically significant, most likely due to an insufficient number of patients studied. Our study does not demonstrate superiority of VAC associated with skin graft over conventional dressings. We observed more complications with VAC (40%) than with conventional dressings (23%) (P=0.06).


Lamprey contractile protein genes mark different populations of skeletal muscles during development.
Agnathan lampreys retain ancestral characteristics of vertebrates in the morphology of skeletal muscles derived from two mesodermal regions: trunk myotomes and unsegmented head mesoderm. During lamprey development, some populations of myoblasts migrate via pathways that differ from those of gnathostomes. To investigate the evolution of skeletal muscle differentiation in vertebrates, we characterize multiple contractile protein genes expressed in the muscle cells of the Japanese lamprey, Lethenteron japonicum. Lamprey actin gene LjMA2, and myosin heavy chain (MyHC) genes LjMyHC1 and LjMyHC2 are all expressed in the developing skeletal muscle cells of early embryos. However, LjMyHC1 and LjMyHC2 are expressed only in cells originating from myotomes, while LjMA2 is expressed in both myotomal and head musculature. Thus, in lampreys, myotomes and head mesoderm differ in the use of genes encoding contractile protein isoforms. Phylogenetic tree analyses including lamprey MyHCs suggest that the variety of muscle MyHC isoforms in different skeletal muscles may correspond to the morphological complexity of skeletal muscles of different vertebrate species. Another lamprey actin gene LjMA1 is likely to be the first smooth muscle actin gene isolated from non-tetrapods. We conclude that, in vertebrate evolution, the different regulatory systems for striated and smooth muscle-specific genes may have been established before the agnathan/gnathostome divergence.


Intestinal morphology of the wild Atlantic salmon (Salmo salar).
The worldwide-industrialized production of Atlantic salmon (Salmo salar) has increased dramatically during the last decades, followed by diseases related to the on-going domestication process as a growing concern. Even though the gastrointestinal tract seems to be a target for different disorders in farmed fish, a description of the normal intestinal status in healthy, wild salmon is warranted. Here, we provide such information in addition to suggesting a referable anatomical standardization for the intestine. In this study, two groups of wild Atlantic salmon were investigated, consisting of post smolts on feed caught in the sea and of sexually mature, starved individuals sampled from a river. The two groups represent different stages in the anadromous salmon life cycle, which also are part of the production cycle of farmed salmon. Selected regions of gastrointestinal tract were subjected to morphological investigations including immunohistochemical, scanning electron microscopic, and morphometric analyses. A morphology-based nomenclature was established, defining the cardiac part of the stomach and five different regions of the Atlantic salmon intestine, including pyloric caeca, first segment of the mid-intestine with pyloric caeca, first segment of the mid-intestine posterior to pyloric caeca, second segment of the mid-intestine and posterior intestinal segment. In each of the above described regions, for both groups of fish, morphometrical measurements and regional histological investigations were performed with regards to magnitude and direction of mucosal folding as well as the composition of the intestinal wall. Additionally, immunohistochemistry showing cells positive for cytokeratins, α-actin and proliferating cell nuclear antigen, in addition to alkaline phosphatase reactivity in the segments is presented.


Extracorporeal electromagnetic shock-wave lithotripsy for salivary gland stones.
Sialoadenectomy for sialolithiasis is necessary when the stone cannot be removed through the salivary duct. In addition, extracorporeal. shock-wave lithotripsy has recently become available for this purpose. The safety and efficacy of this method was assessed in 52 outpatients bearing stones with an average diameter of 6.76 mm in the submandibular or parotid gland. Anesthetics, sedatives, and analgesics were not required. Twenty-four of the 36 patients with submandibular gland calculi and all 16 with parotid sialolithiasis had complete stone disintegration or fragmentation of the calculi, with possible spontaneous clearance. Untoward effects were observed in 15 patients, namely localized skin petecchiae, transitory swelling of the gland, and self-limiting bleeding from the duct. No persistent damage of the salivary glands or adjacent structures was noted during a mean follow-up period of 10 months.


Processing of bacterial antigens for peptide presentation on MHC class I molecules.
Professional antigen-presenting cells (pAPC) can process and present exogenous antigens on major histocompatibility complex class I (MHC-I) molecules. This unusual pathway for antigen presentation may represent a physiologically important step in the course of priming and tolerance induction of CD8+ T cells. In addition, it may play an important role in immunological surveillance for pathogens that survive in vacuolar compartments in APC. The goal of the present review is to discuss recent studies on the processing of bacterial-derived antigens for presentation on MHC-I molecules. The antigen presentation emphasized will include bacteria that remain confined in vacuolar compartments. This is in contrast to antigens derived from bacteria that have intrinsic properties allowing translocation across membranes and access into the classical MHC-I presentation pathway. In particular, presentation of bacterial antigens by dendritic cells (DC) will be emphasized, and MHC-I presentation of antigens derived from apoptotic cells, particularly cells induced to undergo apoptosis by microbial infection, will be presented. Finally, some special aspects of the interaction between bacteria and DC will be discussed as it relates to DC maturation, antigen presentation and T-cell stimulation.


Clinical implications of glucocorticoid receptor studies in childhood acute lymphoblastic leukemia.
We have performed in parallel, in 19 children with acute lymphoblastic leukemia, a quantitative determination of glucocorticoid levels, in vitro steroid induced inhibition of nucleic acid precursors, and a short-term clinical trial of corticosteroids alone, before the treatment was given, which included corticosteroids and other drugs. From our results it appears that high glucocorticoid receptor levels in acute lymphoblastic leukemia of children do not guarantee a clinical response to corticosteroids. On the other hand, glucocorticoid receptors may turn out to be of value in predicting a poor response to corticosteroids only if their levels are considerably low.


Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes, and neurons.
There is good evidence that the kynurenine pathway (KP) and one of its end products, quinolinic acid (QUIN) play a role in the pathogenesis of several major neurological diseases. While QUIN has been shown to be produced in neurotoxic concentrations by macrophages and microglia, the capacity of astrocytes and neurons to produce QUIN is controversial. Using interferon gamma (IFN-gamma)-stimulated primary cultures of human mixed brain cells, we assayed expression of the KP regulatory enzyme indoleamine 2,3-dioxygenase (IDO) and QUIN production by immunocytochemistry. Using IFN-gamma-stimulated purified cultures of neurons, astrocytes, microglia and macrophages, we studied IDO expression by RT-PCR and production of QUIN using mass spectrometry. We found that astrocytes, neurons, and microglia expressed IDO but only microglia were able to produce detectable amounts of QUIN. However, astrocytes and neurons had the ability to catabolize QUIN. This study also provides the first evidence of IDO expression and lack of production of QUIN in culture of primary human neurons.


Magnetoencephalography is feasible for infant assessment of auditory discrimination.
Magnetoencephalography (MEG) detects the brain's magnetic fields as generated by neuronal electric currents arising from synaptic ion flow. It is noninvasive, has excellent temporal resolution, and it can localize neuronal activity with good precision. For these reasons, many scientists interested in the localization of brain functions have turned to MEG. The technique, however, is not without its drawbacks. Those reluctant to employ it cite its relative awkwardness among pediatric populations because MEG requires subjects to be fairly still during experiments. Due to these methodological challenges, infant MEG studies are not commonly pursued. In the present study, MEG was employed to study auditory discrimination in infants. We had two goals: first, to determine whether reliable results could be obtained from infants despite their movements; and second, to improve MEG data analysis methods. To get more reliable results from infants we employed novel hardware (real-time head-position tracking system) and software (signal space separation method, SSS) solutions to better deal with noise and movement. With these solutions, the location and orientation of the head can be tracked in real time and we were able to reduce noise and artifacts originating outside the helmet significantly. In the present study, these new methods were used to study the biomagnetic equivalents of event-related potentials (ERPs) in response to duration changes in harmonic tones in sleeping, healthy, full-term newborns. Our findings indicate that with the use of these new analysis routines, MEG will prove to be a very useful and more accessible experimental technique among pediatric populations.


Mechanisms of human DNA repair: an update.
The human genome, comprising three billion base pairs coding for 30000-40000 genes, is constantly attacked by endogenous reactive metabolites, therapeutic drugs and a plethora of environmental mutagens that impact its integrity. Thus it is obvious that the stability of the genome must be under continuous surveillance. This is accomplished by DNA repair mechanisms, which have evolved to remove or to tolerate pre-cytotoxic, pre-mutagenic and pre-clastogenic DNA lesions in an error-free, or in some cases, error-prone way. Defects in DNA repair give rise to hypersensitivity to DNA-damaging agents, accumulation of mutations in the genome and finally to the development of cancer and various metabolic disorders. The importance of DNA repair is illustrated by DNA repair deficiency and genomic instability syndromes, which are characterised by increased cancer incidence and multiple metabolic alterations. Up to 130 genes have been identified in humans that are associated with DNA repair. This review is aimed at updating our current knowledge of the various repair pathways by providing an overview of DNA-repair genes and the corresponding proteins, participating either directly in DNA repair, or in checkpoint control and signaling of DNA damage.


Adolescents' health status: sex differences among whites and nonwhites.
This study was designed to determine differences in health between sexes in white and nonwhite adolescents. The data are from the Health Examination Survey's large national sample of 12-17-year-olds. Comparisons are made between males and females for whites and non-whites of their scores on scales constituting different but complementary views of their health. Thus, there were scales of items from (a) a clinical study of each subject, (b) interviews with parents about past and present health, and (c) questionnaires from the youths themselves. To these was added a single rating from a school official on the youth's adjustment at school. Three important findings emerged: (1) the health of white adolescent females was somewhat poorer than that of white males; (2) the health of nonwhite females was poorer than the other three sex-race groups; and (3) the correlation of youths' own rating of their health with estimates from others' including clinicians, showed females to be somewhat more accurate than males.


Kinetics of microbial growth and biodegradation of methanol and toluene in biofilters and an analysis of the energetic indicators.
The kinetics of microbial growth and the biodegradation of methanol and toluene in (a) biofilters (BFs), and (b) biotrickling filters (BTFs), packed with inert materials, has been studied and analyzed. The specific growth rate, mu, for the treatment of methanol was 0.037h(-1) for a wide range of operating conditions. In the BF, mu was found to be a function of the methanol and toluene concentrations in the biofilm. In the BF used for treating methanol, mu was found to be affected by (1) the nitrogen concentration present in the nutrient solution, and (2) the kind of packing material employed. The kinetics of the methanol and toluene biodegradations were also analyzed using "mixed order" models. A Michaelis-Menten model type provided a good fit for the elimination capacity (EC) of the BTF treating methanol, while a Haldane model type provided a good fit to the EC of the BF treating methanol and toluene. The carbon dioxide production rate was related to the packed bed temperature and the content of the volatile solids within the biofilm. For the BF, the ratio of temperature/carbon dioxide production rate (PCO(2)) was 0.024 degrees C per unit of PCO(2), and for the BTF it was 0.15 degrees C per unit of PCO(2).


Breaking the Cycle of Health Inequities: The Bioethics of Data.
Social epigenomics measures the mechanisms through which place and context change our biology. Big data science connects, analyzes, and allows inferences from previously disconnected data. Precision medicine promises individually-tailored treatments. Together, these emerging fields are changing the way we discover, decipher, and deliver new science to populations. However, differential participation in and uptake (by adopter type-from innovators to laggards) of the discovering, deciphering, and delivering of these new mechanisms may exacerbate health disparities. Innovators and early adopters are generally from higher-resourced environments. This leads to data and findings biased towards those environments. Such biased data in turn continue to be used to generate new discoveries, further obscuring potentially underrepresented populations, and creating a nearly inescapable cycle of health inequity. We argue that equitable access to representative data is of special moral (bioethical) importance, necessary to break the cycle of health inequities.


Production of diploid and triploid offspring by inbreeding of the triploid planarian Dugesia ryukyuensis.
Triploidy has generally been considered to be an evolutionary dead end due to problems of chromosomal pairing and segregation during meiosis. Thus, the formation of tetraploids and diploids from triploid types is a rare phenomenon. In the present study, we demonstrated that inbreeding of the triploid planarian Dugesia ryukyuensis resulted in both diploid and triploid offspring in nature. In the triploids of D. ryukyuensis, chiasmata between homologous chromosomes were observed in both female and male germ lines. This result suggests that both diploid and triploid offspring of this species are produced bisexually by zygotic fusion between sperm and eggs. Hence, this phenomenon may be a novel mechanism in planarian for escaping the triploid state.


Steroids for idiopathic sudden sensorineural hearing loss.
This is an update of a Cochrane review first published in The Cochrane Library in Issue 1, 2006 and previously updated in 2009.Idiopathic sudden sensorineural hearing loss (ISSHL) is a clinical diagnosis characterised by a sudden deafness of cochlear or retrocochlear origin in the absence of a clear precipitating cause. Steroids are commonly prescribed to treat this condition. There is no consensus on their effectiveness. To determine whether steroids in the treatment of ISSHL a) improve hearing (primary) and b) reduce tinnitus (secondary).To determine the incidence of significant side effects from the medication. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 22 April 2013. We identified all randomised controlled trials (with or without blinding) in which steroids were evaluated in comparison with either no treatment or a placebo. We considered trials including the use of steroids in combination with another treatment if the comparison control group also received the same other treatment. The two authors reviewed the full-text articles of all the retrieved trials of possible relevance and applied the inclusion criteria independently. We graded trials for risk of bias using the Cochrane approach. The data extraction was performed in a standardised manner by one author and rechecked by the other author. Where necessary we contacted investigators to obtain the missing information. Meta-analysis was neither possible nor considered appropriate because of the heterogeneity of the populations studied and the differences in steroid formulations, dosages and duration of treatment. We analysed and reported the quality of the results of each study individually. A narrative overview of the results is presented. Only three trials, involving 267 participants, satisfied the inclusion criteria and all three studies were at high risk of bias. One trial showed a lack of effect of oral steroids in improving hearing compared with the placebo control group. The second trial showed a significant improvement of hearing in 61% of the patients receiving oral steroid and in only 32% of the patients from the control group (combination of placebo-treated group and untreated control group). The third trial also showed a lack of effect of oral steroids in improving hearing compared with the placebo control. However, this trial did not follow strict inclusion criteria for participant selection and analysis of data was limited by significant exclusion of participants from the final analysis and lack of participant compliance to the treatment protocol. No clear evidence was presented in two trials about any harmful side effects of the steroids. Only one study declared that no patients suffered from adverse effects of the steroid treatment. The value of steroids in the treatment of idiopathic sudden sensorineural hearing loss remains unclear since the evidence obtained from randomised controlled trials is contradictory in outcome, in part because the studies are based upon too small a number of patients.


The application of positron-emitting molecular imaging tracers in Alzheimer's disease.
The symptomatology and known pathology of Alzheimer's disease are restricted to the central nervous system. This review details studies of PET tracers aimed at interrogating cholinergic, serotonergic, opiate, benzodiazepine, and inflammatory pathways as well as PET tracers that illuminate amyloid plaques and neurofibrillary tangles in AD. Progress has been remarkable. Together with studies of brain structure with MRI and of functional regional brain activity, e.g., through measures of blood flow and glucose metabolic rate, molecular imaging promises to dramatically alter our understanding of the structural and physiological abnormalities underlying AD symptomatology. A more immediate impact on the diagnosis and treatment evaluation of AD patients in clinical trials is predicted while the possibility of personalized treatment or prevention of AD may not be that far away.


Endothelin-1 promotes corneal epithelial wound healing in rabbits.
This study is an attempt to determine the effect of endothelin-1 (ET-1)-containing eyedrops on the rate of corneal epithelial wound closure in rabbits. After corneal epithelial debridement of about 50-60 mm2 with n-heptanol, eyedrops containing either 10(-8) M ET-1 or 10(-6) M ET-1 were applied at five different times for the next three days. The wound was serially photographed 12, 24, 36, 48, 60 and 72 hours later to measure the extent of healing with a computerized planimeter. The respective wound healing rate at 10(-6) and 10(-8) M ET-1 was 1.293 +/- 0.040 mm2/hour (n = 11) and 1.262 +/- 0.087 mm2/hour (n = 6), respectively. These rates were 29% (p < 0.01) and 26% (p < 0.05) above the control value, 1.005 +/- 0.063 mm2/hour (n = 13). Reepithelialization was not associated with any epithelial hyperplasia, neovascularization or conjunctival hyperemia. These results suggest that ET-1-containing eyedrops could be of therapeutic value in the remedy of corneal epithelial defects.


Evidence for a novel set of small heat-shock proteins that associates with the mitochondria of murine PC12 cells and protects NADH:ubiquinone oxidoreductase from heat and oxidative stress.
Several previously unreported small heat-shock proteins (sHsps) were detected in mitochondria from heat-stressed rat PC12 cells, but not in unstressed controls. Functional inactivation of the mitochondrial sHsps with murine Hsp25 antibody indicated that these sHsps protect NADH:ubiquinone oxidoreductase and NADH dehydrogenase activity (i.e., complex I) in submitochondrial vesicles during heat and oxidative stress. These results (i) confirm the existence of multiple sHsps in mammals and indicate that several of these sHsps associate with the mitochondria, (ii) indicate a conserved function between plant and mammalian mitochondrial sHsps in protecting electron transport during stress, and (iii) suggest that these sHsps may play an important role in diseases whose etiology is based upon oxidative damage of complex I.


Efficacy and tolerability of albiglutide versus placebo or pioglitazone over 1 year in people with type 2 diabetes currently taking metformin and glimepiride: HARMONY 5.
To investigate the efficacy and tolerability of albiglutide, a weekly glucagon-like peptide-1 receptor agonist, when added to metformin and glimepiride in a triple therapy regimen in people with type 2 diabetes mellitus. This was a 156-week, randomized, double-blind, parallel-group, multicentre study. In the present paper we describe the primary results, namely those at 52 weeks. Adult participants (n = 685) were randomly assigned to albiglutide (30 mg/week), pioglitazone (30 mg/day) or placebo. If needed, blinded uptitration of albiglutide (to 50 mg/week) and pioglitazone (to 45 mg/day) was allowed. The participant's current dose of metformin (>1500 mg/day) was maintained throughout. The glimepiride dose (4 mg/day), standardized before randomization, could be decreased if persistent hypoglycaemia occurred. The week 52 model-adjusted difference in change of glycated haemoglobin (primary endpoint) for albiglutide versus placebo was -0.87 [95% confidence interval (CI) -1.07, -0.68]%-units (p < 0.001), and for albiglutide versus pioglitazone it was 0.25 (95% CI 0.10, 0.40)%-units; therefore, not non-inferior. In the albiglutide group only, fasting plasma glucose reduced rapidly in the first 2 weeks. Confirmed hypoglycaemia occurred in 14% of participants on albiglutide, 25% on pioglitazone and 14% on placebo. The mean (± standard error) weight change was -0.42 (±0.2) kg with albiglutide, +4.4 (±0.2) kg (p < 0.001) with pioglitazone, and -0.40 (±0.4) kg with placebo and serious adverse events occurred in 6.3, 9.0 and 6.1% of participants in the respective groups. Injection site reactions occurred in 13% of participants on albiglutide and resulted in treatment discontinuation for four participants (1.4%). Albiglutide, as part of triple therapy, provided effective glucose-lowering and was generally well tolerated.


Molecular origins of lung cancer: prospects for personalized prevention and therapy.
The first Meeting on "Molecular Origins of Lung Cancer--Prospects for Personalized Prevention and Therapy" was held from January 10 to 14, 2010 in San Diego, California. The purpose of the meeting was to discuss important basic, translational, and clinical work aimed at improving lung cancer prevention, detection, and treatment. Topics included drug design, target identification, early detection, cancer stem cells, microRNAs, genome wide approaches to determining risk and outcome, mouse models, and tumor microenvironment. The role of cancer advocates in supporting research was an important component of the meeting. Meeting presentations demonstrated that emerging technologies can molecularly dissect lung cancers that have important relevance for clinical utility. This includes molecular based strategies not only for treatment of established cancers but also individualized and molecularly-based strategies for cancer risk reduction and chemoprevention.


Heart rate variability and urinary catecholamines from job stress in korean male manufacturing workers according to work seniority.
The aim of this study was to evaluate the relationships between job stress and indicators of autonomic nervous system activity in employees of the manufacturing industry. A total of 140 employees from a company that manufactures consumer goods (i.e., diapers and paper towels) were recruited for participation in this study. Job stress was assessed using Karasek's Job Content Questionnaire. Heart rate variability (HRV) was measured using a heart rate monitor, and urinary catecholamines were measured by an HPLC-ECD. Information on demographic characteristics, previous job history, smoking status and alcohol consumption was also collected. Job stress did not have a significant effect on HRV or catecholamines. However, low-frequency HRV was significantly higher in the high-strain group of subjects with a short duration of employment. Low- and high-frequency HRV were higher in the high-strain group than in the low-strain group, but these differences were not statistically significant. The results of the present study indicate that low-frequency HRV was significantly higher in the high-strain group of subjects with a short duration of employment. In addition, the results of this study show that HRV can be used as a potential physiologic indicator of job stress in employees with a short duration of employment.


Generalized smooth muscle hamartoma with multiple congenital anomalies without the "Michelin tire baby" phenotype.
We report a patient with generalized smooth muscle hamartoma who presented with many of the variety of congenital anomalies that have been reported in babies with multiple symmetric circumferential rings of folded skin known as Michelin tire baby (MTB) syndrome, but our patient did not show the MTB phenotype. This constellation of findings in the absence of the MTB phenotype has not been previously reported.


Vibrotactile perception and effects of short-term exposure to hand-arm vibration.
This study clarifies whether the established frequency weighting procedure for evaluating exposure to hand-transmitted vibration can effectively evaluate the temporary changes in vibrotactile perception thresholds due to pre-exposure to vibration. In addition, this study investigates the relationship between changes of the vibrotactile perception thresholds and the normalized energy-equivalent frequency-weighted acceleration. The fingers of 10 healthy subjects, five male and five female, were exposed to vibration under 16 conditions with a combination of different frequencies, intensities, and exposure times. The vibration frequencies were 31.5 and 125 Hz and exposure lasted between 2 and 16 min. According to International Organization for Standardization (ISO) 5349-1, the energy-equivalent frequency-weighted acceleration for the experimental time of 16 min is 2.5 or 5.0 m s(-2) root-mean-square, corresponding to a 8-h equivalent acceleration, A(8), of approximately 0.5 and 0.9 m s(-2), respectively. A measure of the vibrotactile perception thresholds was conducted before the different exposures to vibration. Immediately after the vibration exposure, the acute effect was measured continuously on the exposed index finger for the first 75 s, followed by 30 s of measures every minute for a maximum of 10 min. If the subject's thresholds had not recovered, the measures continued for a maximum of 30 min with measurements taken every 5 min. Pre-exposure to vibration significantly influenced vibrotactile thresholds. This study concludes that the influence on the thresholds depends on the frequency of the vibration stimuli. Increased equivalent frequency-weighted acceleration resulted in a significant change in threshold, but the thresholds were unaffected when changes in the vibration magnitude were expressed as the frequency-weighted acceleration or the unweighted acceleration. Moreover, the frequency of the pre-vibration exposure significantly influenced (up to 25 min after exposure) recovery time of the vibrotactile thresholds. This study shows that the frequency weighting procedure in ISO 5349-1 is unable to predict the produced acute changes in the vibrotactile perception. Moreover, the results imply that the calculation of the 'energy-equivalent' frequency-weighted acceleration does not reflect the acute changes of the vibration perception thresholds due to pre-exposure to vibration. Furthermore, when testing for the vibrotactile thresholds, exposure to vibration on the day of a test might influence the results. Until further knowledge is obtained, the previous practice of 3 h avoidance of vibration exposure before assessment is recommended.


Forward and backward waves in the arterial system, their relationship to pressure waves form.
The purpose of this work was to analyze, in human subjects, the shape of the aortic pressure wave from its forward and backward components calculated by use of Westerhof's model. Twenty-nine patients were studied: 11 normal subjects, 11 hypertensive patients and 7 patients with congestive heart failure. The following measurements and calculations were performed both under control conditions and during either angiotensin infusion in 5 normal subjects or nitroprusside infusion in 6 hypertensive patients: cardiac output, aortic blood pressure (catheter tip micromanometer), blood flow velocity (electromagnetic catheter-tip velocity transducer) in the ascending aorta, aortic impedance and reflection coefficients allowing the calculation of the aortic forward and backward pressure waves. The results show that the shape of aortic pressure wave in hypertensive patients is related to increased arterial wall stiffness which determines greater values and overlap of the forward and backward waves. This result is corroborated by the changes observed during angiotensin infusion in normal subjects. The shape of pressure wave in heart failure patients is dicrotic. This shape is related to smaller values and overlap of forward and backward waves. This appears related to a reduced stroke volume. During peripheral vasodilation the shape of pressure wave in hypertensive patients becomes dicrotic. However, this was mainly related to later backward waves. These results confirm that the shape of pressure waves depends both on the arterial wall stiffness and on the left ventricular performance: mainly on the stroke volume. The calculation of forward and backward waves allows a quantitative analysis of pressure waves.


Intensive training and cardiac autonomic control in high level athletes.
We aimed to evaluate in a longitudinal study the effect of intensive training on cardiac autonomic control in athletes using 24-h heart rate variability analysis. Time and frequency domain measures of heart rate variability were calculated from 24-h Holter monitoring in 15 high level bicyclists (mean age 21 +/- 4 yr) after 1 month of detraining and after 5 months of vigorous training. At the same times echocardiographic left ventricular mass and dimensions and maximal oxygen consumption (VO2max) were assessed. In detrained athletes, VO2max values, left ventricular mass and dimensions, and time and frequency domain measures of vagal modulation of heart rate were higher than in a group of untrained subjects of similar age while heart rate and the low-to-high frequency ratio were lower, indicating an enhanced vagal modulation of heart rate in athletes as compared with that in control subjects. After 5 months of vigorous training, left ventricular mass and dimensions and VO2max increased in athletes, while heart rate decreased further. In contrast, no changes were detectable in time and frequency domain measures of heart rate variability over the entire 24-h and in both waking and sleeping hours. This study demonstrates that an increased cardiac vagal control is detectable in detrained athletes; however, after intensive training, despite a significant decrease in heart rate, time and frequency domain measures of heart rate variability reflecting cardiac vagal control remain unchanged. Thus, other mechanisms than changes in cardiac autonomic control could be involved in determining the profound bradycardia of athletes.


Allocentric spatial memory in humans with hippocampal lesions.
An immersive virtual reality (IVR) system was used to investigate allocentric spatial memory in a patient (PR) who had selective hippocampal damage, and also in patients who had undergone unilateral temporal lobectomies (17 right TL and 19 left TL), their performance compared against normal control groups. A human analogue of the Olton [Olton (1979). Hippocampus, space, and memory. Behavioural Brain Science, 2, 315] spatial maze was developed, consisting of a virtual room, a central virtual circular table and an array of radially arranged up-turned 'shells.' The participant had to search these shells in turn in order to find a blue 'cube' that would then 'move' to another location and so on, until all the shells had been target locations. Within-search errors could be made when the participants returned to a previously visited location during a search, and between-search errors when they revisited previously successful, but now incorrect locations. PR made significantly more between-search errors than his control group, but showed no increase in within-search errors. The right TL group showed a similar pattern of impairment, but the left TL group showed no impairment. This finding implicates the right hippocampal formation in spatial memory functioning in a scenario in which the visual environment was controlled so as to eliminate extraneous visual cues.


[Sample technique in cytology (author's transl)].
Modern theory and experience question the reliability and suitability of sampling per judgment being the method for the evaluation of the percentage of cells in clinical cytology till now. For the reduction of this gap empirical studies were undertaken in order to receive proper estimates of blood smears. A simple method for the differential blood count is to take 30 or more strips of the width of the field of vision of the microscope perpendicular to the smearing direction as sampling units at random or by systemtaic selection with a random starting point. For the class of cells under consideration as well as for whole the cell population on the slide, the coefficient of variation of the mean of the cells within different strips has to be less than 0,1. Smears of a width of 10 mm instead of the usual 22 mm seems to be preferable. Under such conditions more than 1.000 cells are to be counted for a reliable estimate of the more frequent classes of cells. It is not supposed that this tedious method will be carried out by technicians but modern apparatus are presumed to give consistent estimates in such a way.


[Perimetry in chiasmal syndrome -Liminal and surpraliminal stimuli (author's transl)].
The value of static and kinetic perimetry with white and colored stimuli in chiasmal syndrome seems to be equal. The presentation of evenly moving supraliminal targets allows for an evaluation of sensory disturbance. This procedure is even more subjective, variable and difficult to perform accurately. It may reveal, however, more discrete sensory pathology than conventional perimetry can do. Red is often better than other colors, spectral colors are better than pigment colors. The sector-shaped pattern of disturbance of sensation might relfect the arrangement of nerve-fibers in the optic chiasm.


Crystal structure of ribonuclease Ms (as a ribonuclease T1 homologue) complexed with a guanylyl-3',5'-cytidine analogue.
A ribonuclease T1 homologue, ribonuclease Ms (RNase Ms) from Aspergillus saitoi, has been crystallized as a complex with a substrate analogue GfpC where the 2'-hydroxyl (2'-OH) group of guanosine in guanylyl-3',5'-cytidine (GpC) is replaced by the 2'-fluorine (2'-F) atom to prevent transesterification. The crystal structure of the complex was solved at 1.8-A resolution to a final R-factor of 0.204. The role of His92 (RNase T1 numbering) as the general acid catalyst was confirmed. Of the two alternative candidates for a general base to abstract a proton from the 2'-OH group, His40 and Glu58 were found close to the 2'-F atom, making the decision between the two groups difficult. We then superposed the active site of the RNase Ms/GfpC complex with that of pancreatic ribonuclease S (RNase S) complexed with a substrate analogue UpcA, a phosphonate analogue of uridylyl-3',5'-adenosine (UpA), and found that His12 and His119 of RNase A almost exactly coincided with Glu58 and His92, respectively, of RNase Ms. Similar superposition with a prokaryotic microbial ribonuclease, RNase St [Nakamura, K. T., Iwahashi, K., Yamamoto, Y., Iitaka, Y., Yoshida, N., & Mitsui, Y. (1982) Nature 299, 564-566], also indicated Glu58 as a general base. Thus the present comparative geometrical studies consistently favor, albeit indirectly, the traditional as well as the most recent notion [Steyaert, J., Hallenga, K., Wyns, L., & Stanssens, P. (1990) Biochemistry 29, 9064-9072] that Glu58, rather than His40, must be the general base catalyst in the intact enzymes of the RNase T1 family.


Pediatric airway control and ventilation.
Emphasis on a clear airway is a primary requisite for effective CPR. Airway control in the trauma victim needs special consideration of the possibility of associated cervical vertebrae and spinal cord injury; thus, modification of the patient positioning for transport is essential. Emphasis on visualization of chest movement is the most important factor in assessing adequacy of ventilation. Experience in the use of bag-valve-mask devices requires appropriate instruction and on-going practice. Small bag volume devices limit the ability to provide adequate tidal volumes and prolong inspiratory times. Tracheal intubation provides optimal airway management. In-field use of this procedure will depend upon the skill and experience of the operator. Validation of correctness of tracheal tube placement is critical; seeing the tube pass the glottic opening on laryngoscopy, bilateral and equal chest movement, auscultation of breath sounds in the chest. Methods to measure end-tidal CO2 as a valuable check for tube position is a useful adjunct but must not be relied upon. Foreign body management continues to be controversial and remains unchanged for the present; ie, the infant < 1 year of age the recommendations are back blows followed by chest thrusts. Above 1 year of age, abdominal thrusts (Heimlich maneuver) is recommended.


Adult mesenchymal stem cells and their potency in the cell-based therapy.
Recent advances in the field of regenerative medicines manifested the unique properties of stem cells including the ability of self-renewal and differentiation to make them available for their replacement in tissue injury. Mesenchymal stem cells (MSCs) are important tools in treating immune disorders and in tissue repair due to their multipotency, immunosuppressive properties, and production of cytokines or growth factors. MSC-mediated therapy is a fast-growing field that has proven safe and effective in the treatment of various degenerative diseases and tissue injuries. Generation of induced pluripotent stem (iPS) cells holds a great promise for regenerative medicine and other aspects of clinical applications. The mechanisms governing multipotency in MSCs are not well understood. This review mainly throws light on the biology of MSCs, including their efficiency in treating several diseases and also the progress of the use of iPSC-derived MSC widely in the clinic.


Experimental demonstration of quantitative imaging beyond Abbe's limit with optical diffraction tomography.
Optical diffraction tomography (ODT) is a recent imaging technique that combines the experimental methods of phase microscopy and synthetic aperture with the mathematical tools of inverse scattering theory. We show experimentally that this approach permits us to obtain the map of permittivity of highly scattering samples with axial and transverse resolutions that are much better than that of a microscope with the same numerical aperture.


General and specific mortality among the elderly during the 2003 heat wave in Genoa (Italy).
The effects of heat waves on health can be serious for elderly persons, especially those in urban areas. We investigated in-depth the mortality excess during the 2003 heat wave among elderly persons (>74 years) in the City of Genoa (Italy). The excess in general mortality was calculated for the period July 16-August 31, as the ratio of observed to expected deaths. To evaluate "harvesting", we compared observed and expected mortality in the period September 2003-April 2004. We also studied the relationship between mortality and climatic conditions considering daily maximum temperature and Humidex discomfort degrees, as well as "lag-time". For cause-specific mortality, we considered all pathologies reported on the death certificate. The excess in general mortality was significant and was greatest in the first half of August. During Summer 2003, in Genoa the climatic conditions (described in terms of maximum temperature and Humidex Index) were extremely hot; regarding lag-time, the greatest correlation between the number of observed deaths and the maximum temperature values was observed for the three preceding days (rho=0.568; significance level<0.01). The prominent causes of death, for which an excess was observed, were cerebrovascular diseases, severe respiratory diseases, severe renal diseases, dementia; moreover, certain pathologic conditions and symptoms, usually not lethal, were also frequent causes of death (e.g., hypovolemia, hyperpyrexia, decubitus ulcers and immobilization syndrome). The results of this study confirm the relationship between the heat waves and death among elderly, stressing that, because of their poorer physical health and the prevalence of cognitive disturbances that hinder risk perception, it is necessary to properly care for them during heat waves.


Analysis of 6-keto PGF1 alpha, 5-HETE, and LTC4 in rat lung: comparison of GM/MS, RIA, and EIA.
The recent availability of fast and sensitive radioimmunoassay (RIA) and enzyme immunoassay (EIA) procedures to measure icosanoids has led to utilization of these techniques by many investigators. A major concern has been that techniques based on immunoreactivity may lack specificity, in particular if complex biologic fluids or tissue extracts are evaluated. The purpose of this investigation was the comparison of icosanoid measurements obtained either with EIA or RIA with those obtained by gas chromatography/mass spectrometry (GC/MS). Rats were injected with Salmonella enteritidis endotoxin, killed at various times after the injection and the lung extract assayed for 6-keto-PGF1 alpha, 5-HETE and LTC4. By EIA lung tissue was found to contain large quantities of 6-keto-PGF1 alpha after endotoxin stimulation. Comparisons made between EIA and GC/MS analysis showed good correlation between 6-keto-PGF1 alpha amounts in lung as determined by each technique. It was also determined that little purification of lung extract was needed to obtain reliable quantitation of 6-keto-PGF1 alpha, probably due to the specificity of the antibody and the large quantity of this prostaglandin produced. Crudely purified (Sep-Pak) lung extracts gave 5-HETE levels by RIA which were highly correlated with GC/MS values, but RIA values were 70% higher than those obtained by GC/MS. The presence of other components in lung extract which cross react with this 5-HETE antibody was probably responsible for the higher values obtained by RIA. LTC4 was measured by immunoassay in crude lung extracts, as well as after Sep-Pak purification and HPLC purification. LTC4 levels were identical in unpurified lung extract and after Sep-Pak purification, but decreased substantially after HPLC purification. Thus, by validating the icosanoid immunoassays, we have found that they can give accurate and reproducible results in lung tissue, although LTC4 and 5-HETE must be purified prior to analysis.


The role of culturally competent communication in reducing ethnic and racial healthcare disparities.
Promoting culturally competent communication at the provider, care institution, health plan, and national levels is likely to contribute to success in reducing racial and ethnic disparities in the receipt of high quality care. Although some health plans recently have shown interest in addressing racial and ethnic disparities in care, very few have addressed how health plans can improve their cultural competency to reduce disparities. This commentary summarizes the importance of culturally competent communication across several levels of the healthcare system and details concrete steps that managed care organizations can take to maximize their ability to provide culturally competent communication and care.


Arrest of chlorophyll synthesis and differential decrease of Photosystems I and II in a cyanobacterial mutant lacking light-independent protochlorophyllide reductase.
The chlL gene encodes one subunit of the light-independent protochlorophyllide reductase. A chlL-lacking mutant of the cyanobacterium Plectonema boryanum is unable to synthesize chlorophyll (Chl) in the dark, causing Chl synthesis to become light-dependent as in angiosperms. When the mutant cells were cultivated heterotrophically in the dark, Chl synthesis was arrested and the Chl content decreased exponentially in reverse profile to cell propagation, indicating that most of the pre-existing Chl was recruited for daughter cells. During this 'etiolating' process the Chl content became less than 0.5% of the original level. In parallel to this there was a decrease in the activity of Photosystem I (PSI), the amount of its core Chl-binding subunits, PsaA/PsaB, and a peripheral subunit, PsaC. Levels of transcripts for these subunits were not significantly changed upon the arrest of Chl synthesis. In contrast, Photosystem II (PSII) was maintained to a significant extent in terms of activity and protein levels of D1 and CP47 until a late stage of the etiolation, implying that PSII is newly synthesized though Chl synthesis was arrested. Low-temperature (77 K) fluorescence spectral analysis supported a selective decrease in Chl associated with PSI. Taken together, it is suggested that the pre-existing Chl molecules in periphery of PSI could be released and re-distributed for PSII biosynthesis in the etiolating cyanobacterial cells.


Enhanced quantum correlations in bound higher-order solitons
Quantum effects in N-bound solitons can be drastically enhanced compared to the fundamental soliton. In particular, the spectral photon-number correlations are much stronger. The formation of spectral domains of almost perfect positive and negative correlations is predicted. Criteria that are based on the Cauchy-Schwarz inequality are used for studying nonclassical correlations. Interferences between different soliton components of the N-bound solution being responsible for the strong changes in the coherent amplitude may also be a mechanism for the strong correlations. The results offer novel possibilities of producing light with highly nonclassical properties.