Total caseload of a colorectal surgical unit: baseline measurement and identification of areas for efficiency gains.
Resource limitations are a concern in most modern public hospital systems. The aim of this study is to prospectively quantify the total caseload of a tertiary colorectal surgery unit to identify areas of redundancy. Data was collected prospectively at all points of clinical care (outpatient clinic, inpatient referrals, operating theatre and endoscopy) between March 2014 and March 2015 using specifically designed templates. The final data was analysed using descriptive statistics. During the study period, 4012 patient episodes were recorded: 2871 in outpatient clinic, 186 as emergency patient referrals, 541 at colonoscopy and 414 at surgery. The largest component of the caseload was made up primarily of colonoscopy results follow-up, protocol review for previous cancer or polyps and post-operative review. Sixty-eight percent of these episodes did not result in any active intervention such as further tests or surgery. Most new outpatient referrals were undifferentiated, with the most common indications being minor rectal bleeding, non-specific gastrointestinal symptoms, and minor non-bleeding anorectal problems. Of the new referrals, 56 % were booked for a colonoscopy, and only 13.3 % were booked directly for elective surgery. A large component of the caseload of a tertiary colorectal surgery unit is made up of post-colonoscopy, post-operative, and surveillance protocol follow-up, with a significant proportion of patients not requiring any active intervention. The majority of new referrals are undifferentiated and result in a low rate of direct booking for operative intervention. Rationalisation of this resource using evidence-based methods could reduce redundancy, workload, and cost.


Monosomy 22 in a fibrothecoma.
We found a 45,XX, -22 karyotype as the sole chromosome change in a fibrothecoma of a 67-year-old woman. These cytogenetic findings are discussed in the light of relevant cytogenetic and pathology literature data on ovarian sex cord tumors.


The interposito-rubrospinal system. Anatomical tracing of a motor control pathway in the rat.
The cerebello-rubromotor pathway, impinging on both spinal and facial motor nuclei, has been traced in the rat, using the bidirectional transport of horseradish peroxidase-wheat germ agglutinin conjugate. After injection of the tracer in the red nucleus (NR), retrograde labelling shows a topical arrangement of the cerebellorubral connection. The nucleus lateralis projects to the parvocellular NR (NRp) and the nucleus interpositus to the magnocellular NR (NRm). The nucleus interpositus anterior (NIA) reaches the entire NRm and this projection is topographically arranged: the medial NIA sends fibres ventrally, the lateral NIA dorsally. The medial two-thirds of the nucleus interpositus posterior (NIP) project only to the medial aspect of the NRm, with no apparent organization. No connection has been found between the lateral third of NIP and the NRm. After injection of the tracer in the spinal cord or the nucleus of the facial nerve, retrograde labelling is observed almost throughout the entire caudorostral extent of the NR, although labelling is more scant in NRp than in NRm. Rubrospinal and rubrofacial projections are somatotopically arranged in the dorsoventral direction: ventrolateral regions of NR reach the lumbar cord, medioventral regions the lower cervical levels, intermediary regions the upper cervical levels and finally the dorsalmost part of the NR projects to the nucleus of the facial nerve. After injection of the tracer in the cerebellar nuclei, anterograde labelling in the NR shows that interpositorubral connections determine two subregions in the NR: a lateral one under the exclusive control of the NIA, and a medial one under the control of both NIA-NIP afferents. It confirms in addition the topography of the NIA-NRm projection and shows the preponderant participation of the NIA afferents to the interpositorubral connection. Thus, it appears from our results that the cerebellorubral arrangement matches, to a great extent, the "rubromotor" efferent organization.


Self-generated elaboration and spacing effects on incidental memory.
The purpose of the present study was to investigate the effect of self-generated elaboration on incidental memory as a function of type of presentation (massed vs spacing). Subjects generated answers to "why" questions for target sentences in a self-generated elaboration condition. They then rated the appropriateness of the answers to the questions presented by the experimenter in an experimenter-provided elaboration condition. This procedure was followed by free recall tests. The target sentences were presented twice, in either a massed presentation without intervening items between the first and the second presentation or spaced presentation in which 5 items appeared between the two presentations. The self-generated elaboration effect, namely, higher recall, of self-generated elaboration over experimenter-provided elaboration, occurred with spaced but not with massed presentation. So, self-generated elaboration was facilitated in the spaced presentation because the time between the first and the second presentations led to richer encoding of each target.


[Non-Hodgkin's lymphoma of the parotid gland].
Since 1969 we have seen 17 patients with non-Hodgkin's lymphoma of the parotid gland. Retrospective analysis of these patients reveals that the primary diagnosis was established in 14 patients by parotid surgery. In 10 (58.8%) cases there was a single focus of NHL in the parotid gland proven by extensive medical and radiological examinations. Histology showed that 14 (82.3%) of the tumors were low grade and 3 (17.7%) were high grade (Kiel classification). In 5 specimens myoepithelial sialadenitis was found in the parotid gland tissue. Six patients died within 1.5 years on average, 4 of them without evidence of disease. Four of the 7 patients alive have been followed for an average of 3.1 years without evidence of disease. Primary radiation of the parotid region in stage IE in cases of parotid gland NHL seems to be an effective therapy. NHL presenting in myoepithelial sialadenitis seems to be rare, but offers the opportunity of observing an organ specific malignant process.


[Liver stiffness measured by acoustic radiation force impulse imaging in assessing hepatic functional reserve in patients with space-occupying lesions in the liver].
To investigate the value of liver stiffness measured by acoustic radiation force impulse imaging(ARFI) in assessing hepatic functional reserve in patients with space-occupying lesions in the liver. Sixty-three patients with space-occupying lesions in the liver were enrolled. Liver stiffness (LS) measurements with ARFI and indocyanine green(ICG) retention test were performed in the same day, and plasma clearance rate of indocyanine green(ICG-K), ICG retention at 15 minutes(ICGR15) as well as 10 effective values of LS were recorded. The correlation between Child-Pugh score, ICGR15, ICG-K, and LS were evaluated. The LS measurements with ARFI failed in one patient. A strong correlation between LS and ICGR15(r=0.789, P<0.01) and an inverse correlation between LS and ICG-K(r=-0.738, P<0.01) were observed. Besides, there was a significant correlation between LS measurements and Child-Pugh score(r=0.929, P<0.01) . The LS significantly differed among patients with Child-Pugh class A, B, and C(P<0.01) . ARFI is a simple, feasible and non-invasive method for assessing hepatic functional reserve in patients with space-occupying lesions in the liver.


Nitrate, fumarate, and oxygen as electron acceptors for a late step in microbial heme synthesis.
Nitrate can serve as anaerobic electron acceptor for the oxidation of protoporphyrinogen to protoporphyrin in cell-free extracts of Escherichia coli grown anaerobically in the presence of nitrate. Two kinds of experiments indicated this: anaerobic protoporphyrin formation from protoporphyrinogen, followed spectrophotometrically, was markedly stimulated by addition of nitrate; and anaerobic protoheme formation from protoporphyrinogen, determined by extraction procedures, was markedly stimulated by addition of nitrate. In contrast, anaerobic protoheme formation from protoporphyrin was not dependent upon addition of nitrate. This was the first demonstration of the ability of nitrate to serve as electron acceptor for this late step of heme synthesis. Previous studies with mammalian and yeast mitochondria had indicated an obligatory requirement for molecular oxygen at this step. In confirmation of our previous preliminary report, fumarate was also shown to be an electron acceptor for anaerobic protoporphyrinogen oxidation in extracts of E. coli grown anaerobically on fumarate. For the first time, anaerobic protoheme formation from protoporphyrinogen, but not from protoporphyrin, was shown to be dependent upon the addition of fumarate. The importance of these findings is 2-fold. First, they establish that enzymatic protoporphyrinogen oxidation can occur in the absence of molecular oxygen, in contrast to previous observations using mammalian and yeast mitochondria. Secondly, these findings help explain the ability of some facultative and anaerobic bacteria to form very large amounts of heme compounds, such as cytochrome pigments, when grown anaerobically in the presence of nitrate or fumarate. In fact, denitrifying bacteria are known to form more cytochromes when grown anaerobically than during aerobic growth. An unexpected finding was that extracts of another bacterium, Staphylococcus epidermidis, exhibited very little ability to oxidize protoporphyrinogen to protoporphyrin as compared to E. coli extracts. This finding suggests some fundamental differences in these two organisms in this key step in heme synthesis. It is known that these two facultative organisms also differ in that E. coli synthesizes cytochrome during both aerobic and anaerobic growth, while Staphylococcus only synthesizes cytochromes when grown aerobically.


Non-Hodgkin's lymphoma presenting as Pancoast's syndrome.
Pancoast's syndrome is generally caused by primary or metastatic epithelial tumors. Other causes of the syndrome are unusual but well described. The present case report describes a rare case of Pancoast's syndrome caused by non-Hodgkin's lymphoma. This report emphasises the importance of establishing a firm pathologic diagnosis of the etiology of Pancoast's syndrome before instituting treatment.


Can radiation-induced apoptosis be modulated by inhibitors of energy metabolism?
To determine the effect of the inhibitors of energy metabolism, 2-deoxyglucose (2DG) and sodium azide, on radiation-induced apoptosis. Radiation-induced apoptosis was determined in U937 monocytic leukaemia cells exposed to energy inhibitors post-irradiation. Apoptosis was scored microscopically using morphological criteria. Glycolysis was determined by assessing glucose consumption and lactate production. Adenine nucleotide levels were measured using a luciferase assay after enzymatic conversion to ATP. Respiration was measured using a Clark-type oxygen electrode. In addition to their apoptosis-inducing properties, both 2DG and azide modified post-irradiation apoptosis. 2DG induced apoptotic radiosensitization after exposure to lower concentrations (5 mM, 10 mM) up to 20 h post-irradiation while a level of radioprotection was found after 5 h exposure to higher doses up to 100 mM. By contrast, all doses of azide examined (5-50 mM) induced apoptotic radioprotection at all times examined. Glycolytic flux and ATP levels fell rapidly with increasing 2DG dose but energy charge remained unchanged. Glycolysis was less influenced by azide, with ATP levels being initially maintained after exposure but decreasing in a dose-dependent manner at 3 h post-irradiation. However, energy charge was unaffected by azide at the concentrations examined. Both 2DG and azide can influence radiation-induced apoptosis possibly through their effects on glycolysis and ATP levels. We suggest that modulation of energy metabolism provides mechanistic insight into radiation-induced apoptotic pathways.


Determination of (+)-alpha-tocopherol in environmental tobacco smoke.
A high-performance liquid chromatographic method is described for the quantitation of (+)-alpha-tocopherol in the particulate phase of environmental tobacco smoke (ETS) collected on a 1-micron pore size Fluoropore membrane. A methanol (MeOH) extract of the membrane, which can be used for four other ETS procedures, is analyzed for (+)-alpha-tocopherol on a reversed-phase column with fluorescence detection at selective wavelengths of 280 nm excitation and 330 nm emission. A mobile phase of MeOH and water is used. The method is reproducible with a relative standard deviation (%) of about 12. Recovery is 88%, and the procedure is capable of detecting greater than 0.04 microgram/m3 (+)-alpha-tocopherol in ETS. A comparison of the ETS from five commercially available cigarettes shows similar (+)-alpha-tocopherol concentrations. A cigarette that primarily heats tobacco yields about 6% of that amount of (+)-alpha-tocopherol found in ETS from tobacco-burning cigarettes. (+)-alpha-Tocopherol can be used as a marker for ETS respirable suspended particles (RSP) because it is found at a consistent amount in ETS RSP of 0.29%. However, sufficient amounts of RSP would have to be generated in order to detect (+)-alpha-tocopherol.


Variations in surgical anatomy of the endolymphatic sac.
Twenty-nine specimens of the extraosseous portion of the human endolymphatic sac (ES) were serially sectioned longitudinally. The length and width of the extraosseous ES were measured and the surface area was calculated. As the specimens included the sigmoid sinus (SS), the relationship between the ES and the SS was analyzed. The extraosseous ES varied considerably in size. The lumen either consisted of a single tube or was subdivided into several tubules. The distal part of the ES overlapped the SS in one third of the specimens. The results indicate that a minute extraosseous ES could explain the sometimes difficult task of localizing this structure at ES surgery. The great variability in size might perhaps also explain the varying results of this surgery.


Social responsibility and global health: lessons from the Rio Olympics Zika controversy.
The outbreak of Zika virus infection in the Americas and its possible association with microcephaly raised several concerns among global health authorities regarding the organisation of the Olympic and Paralympic Games scheduled for August and September 2016, in the city of Rio de Janeiro, Brazil. It generated an international controversy over the continuation of the Games with debates on the ethical principle of social responsibility. Based on the principles of social responsibility and health in the Universal Declaration of Bioethics and Human Rights, the present comment ponders on the application of such principles in the context of mega-events and global health.


[BIPOLAR DISORDER AS A MULTI-SYSTEM ILLNESS].
Bipolar disorder is a chronic condition, characterized by high distress in patients and high suicide rates (30%). Most patients suffer from medical and other psychiatric comorbidities, which worsen the psychiatric symptoms and decrease the likelihood of remission. More than 70% of bipolar patients have cardio-metabolic symptoms, with higher rates compared to other psychiatric disorders. Cardiovascular disease is the major cause of high mortality rates in these patients, with 1.5-2 fold increased risk of mortality, compared to the general population without psychiatric symptoms. The rates of cardiovascular risk factors and their resulting increased mortality rates are similar to those found in schizophrenia. In addition to cardio-metabolic conditions, 50% of patients with bipolar disorder suffer from other medical symptoms, which are also associated with worse outcomes. Therefore, the current perspective is that bipolar disorder is not only a psychiatric disorder, but rather a multi-system illness, affecting the entire body. The optimal treatment for these patients should include diagnosis, monitoring and treatment of both psychiatric and physical symptoms, which would improve their prognosis.


Cognitive distortions of somatic experiences: revision and validation of a measure.
The article reports on the revision of the Cognitive Errors Questionnaire (CEQ). The CEQ which was originally developed to measure cognitive distortions specific to chronic pain, has been significantly shortened and made applicable to a wider range of somatic problems. The Cognitive Errors Questionnaire-Revised (CEQ-R) contains two subscales: Somatic--distortions specific to somatic experiences; and General--distortions to everyday life events. Validation of the scale with CFS, depressed, and chronic pain groups and healthy controls confirms the CEQ-R loads onto general and somatic factors. Both subscales have high internal consistency and good test-retest reliability. The pattern of subjects' responses to the CEQ-R scores showed that the depressed group scored significantly higher on the General CEQ-R scale than the other groups, whereas the CFS and chronic pain groups scored higher than healthy controls on the Somatic CEQ-R. Somatic CEQ-R scores showed a significant decrease over the course of a pain management program, with a concomitant decrease in disability and depression scores. Further analyses showed the Somatic CEQ-R to be significantly related to self and symptom focusing, whereas the General CEQ-R was found to be significantly correlated with higher depression, lower self-esteem, and self focusing. The CEQ-R may be a useful instrument to examine the relationship between cognitive distortions and disability in a variety of illnesses, and to differentiate primary depression from overlapping somatic disorders.


Cervical screening: time to change the policy.
1. In 1991, the "organised approach to preventing cancer of the cervix" recommended Pap smears every two years for women aged 18-70 years who have ever been sexually active. 2. The two-year interval was a compromise step towards the scientifically supported three-year interval, as many influential groups were strongly attached to annual screening. When other components of the organised approach were in place, the policy was to be reviewed. 3. Since the safeguards in the "organised approach" have been proven effective, it is appropriate to change the policy to recommend a three-year interval. Increasing the interval would allow more resources to be allocated to enrolling women currently underscreened and to evaluating and improving the program. 4. The age of commencing smears could also be reconsidered to reflect the balance of potential benefits and harm in young women, for whom cancer is very rare but follow-up investigation common. 5. If consensus is not reached within the profession, an evidence-based decision may need to be made at the political level.


[Effect of adrenocorticotropic hormone (ACTH4-10) on information network of the cardiovascular systems].
The polyparametric description of adaptation syndromes in students using a uniform set of parameters of cardiovascular system and their relationships is presented. An analog of adrenocorticotropic hormone (ACTH4-10) is shown to exert varying effects on the development of different adaptation syndromes. Adaptation syndromes characterized by moderately active physiological processes (as judged by EGG, rheovasogram, respiration rate) and lowered vascular tonus were associated with marked improvement of the health status.


Propolis aqueous extract preserves functional integrity of murine intestinal mucosa after exposure to ionizing radiation.
The ability of a specially prepared water propolis extract (PWE) to preserve the functional activity of the intestinal mucosa after radiation exposure was studied. PWE was given orally (650 mg/kg) to rats five days prior to irradiation by 6 Gy and continued for further two days. Rats were sacrificed 24h later, intestinal segments were examined histologically and homogenates were used to assess relevant biochemical parameters reflecting intestinal injury. Irradiation led to a rise in the histological damage score, a rise in tissue TNF-α and TBARS, and a decrease in sucrase, alkaline phosphatase, GSH and cholecystokinin as well as a decrease in plasma citrulline. The findings reflect a decrease in intestinal functional activity. PWE preserved the intestinal integrity and largely protected against the changes induced in the histology damage score and all parameters measured, possibly as a result of the antioxidant and anti-inflammatory action of its caffeic acid content.


Detecting symmetric patterns in EEG data: a new method of analysis.
Theoretical models of higher cognitive function predict that cortical activity will exhibit families of spatial-temporal patterns of activity whose individual members are related to each other by specific symmetry transformations. In the trion model, it is suggested that these inherent symmetries play a vital role in how we think and reason. We have developed a method of analysis (SYMMETRIC analysis), which detects families of patterns in EEG data, and characterizes the symmetry relationships between members of those pattern families. Using this analysis, significant symmetry families have been found in EEG and single unit spike train data. If symmetry is a crucial aspect of brain function, it is possible that different pathologies are associated with specific types of symmetry relationships in brain activity that could be detected in EEG data by a SYMMETRIC analysis.


Comparison of two-hand kettlebell exercise and graded treadmill walking: effectiveness as a stimulus for cardiorespiratory fitness.
Prevailing interest in the use of kettlebell (KB) exercises for rehabilitation and improvement of muscular strength has led to several recent studies, some suggesting that KB exercise may be useful for improvement of cardiorespiratory fitness. The purpose of this study was to determine whether KB exercise would produce similar cardiovascular stress to that of walking and thus provide an additional exercise mode for the improvement of cardiorespiratory fitness. It was hypothesized that a moderate-intensity, continuous KB protocol, would produce similar metabolic and cardiorespiratory responses as a brisk bout of graded treadmill (TM) walking, but greater rating of perceived exertion (RPE). Ten novice volunteers (5 men, 5 women) completed a preliminary session to determine body composition and VO2max and to familiarize participants with standardized KB exercise technique. Subsequently, they completed a 30-minute KB session that included 3 continuous 10-minute sets of 10 KB swings followed by 10 sumo deadlifts, with 3-minute rests between 10-minute exercise periods. The third session was a 30-minute TM regimen that began at the walking speed and 4% grade that matched the VO2 from the KB session and included 3-minute rest intervals after 10-minute TM exercise periods. VO2, respiratory exchange ratio, kcal·min, and blood pressure were similar for KB and moderate-intensity TM exercise, but RPE and heart rate were greater during KB exercise. Data indicate that a KB routine consisting of 2-hand swings and sumo deadlifts with 3-minute rest periods produces similar metabolic responses to those of a moderate-intensity TM walking protocol designed for the improvement of aerobic fitness.


The risk of unintentional out-of-network encounters with hospital-based physicians at in-network hospitals.
When hospital-based specialists including emergency physicians, anesthesiologists, pathologists and radiologists are not included in the same insurance networks as their parent hospitals, it creates confusion and leads to unexpected costs for patients. This study explored the frequency with which hospital-based physicians at academic medical centers are not included in the network directories for the same insurance networks as their parent teaching hospitals. We studied teaching hospitals with residency programs in all four hospital-based specialties. Using insurance plan provider directories, we determined whether each teaching hospital was in-network for randomly selected locally available insurance plans offered through the federal and state marketplace exchanges. For each established hospital-network relationship, we then determined whether hospital-based specialists were included in the provider network directory by searching for the name of each specialty's residency program director and the name of the physician practice group. We identified 79 teaching hospitals participating in 144 locally available insurance plan networks. Hospital-based specialist inclusion in these hospital-network relationships was: emergency physicians: 50.0% (CI: 40%-59%); anesthesiologists: 50.0% (CI: 42%-58%); pathologists: 45.4% (CI: 37%-54%); and radiologists: 55.1% (46%-64%). Inclusion of all four hospital-based specialties occurred in only 45.0% (CI: 36%-54%) of the hospital-network relationships. For insurance plans offered through the federal and state marketplace exchanges, hospital-based specialists frequently are not included in the directories for the insurance networks in which their parent teaching hospitals participate. Further research is needed to explore this issue at non-academic hospitals and for off-exchange insurance products, and to determine effective policy solutions.


The use of violacein to study biochemical behaviour of Saccharomyces cerevisiae cells.
Violacein, a biochemical compound produced by Chromobacterium violaceum which has antichagasic properties, was used to study biochemical behaviour of Saccharomyces cerevisiae cells. At 20 microM and 40 microM, violacein did not alter the membrane potential (deltapsi) of S. cerevisae cells, which means that the integrity of the cell membrane was maintained. On the other hand, at 60 microM and 80 microM, violacein produced significant alterations in the membrane potential. This information will be very useful in using S. cerevisiae cells as a model to test the toxicity of new drugs before using in animals or human beings.


[Proteomic analysis of mitochondrial proteins in hydroxycamptothecin-treated SMMC-7721 cells].
To investigate the differentially expressed mitochondrial proteins in hydroxycamptothecin (HCPT)-treated SMMC-7721 cells by comparative proteomic analysis. Apoptosis of SMMC-7721 cells were induced by using HCPT and their mitochondria were isolated with a mitochondria isolation kit for cultured cells. Three different solubility protein fractions were extracted with ReadyPrep Sequential Extraction Kit and were separated by two-dimensional gel electrophoresis (2-DE). PDQuest software was used to differentiate mitochondrial proteins between control cells and HCPT-treated cells. Matrix assisted laser desorption/ionization time of flying mass spectrometry (MALDI-TOF-MS) was used to identify some of the different proteins. Highly purified mitochondria and high resolution 2-DE patterns of the proteins were obtained. Forty-four mitochondrial protein spots from the HCPT-treated cells showed different expressions compared to those of the control cells. Twenty of the different protein spots were analyzed by MALDI-TOF-MS. Differently expressed mitochondrial proteins in HCPT-treated cells and control cells were obtained in this study. This will be of help to understand the mechanism by which HCPT induces cell apoptosis.


Ocular toxicity in beagle dogs with an experimental fluoromethane-sulfonanilide sympathomimetic agent.
ocular lesions were detected in Beagle dogs receiving high doses of BA6650, an experimental fluoremethane-sulfonanilide sympathomimetic agent, during a preclinical safety evaluation study. The oral dose of BA6650 was increased during the 14-day study from 20 mg/kg twice daily (bid) for days 1-3 to 30 mg/kg bid for days 4-6 and finally to 40 mg/kg bid for days 7-14. Two males and two females received BA6650 while one male and one female were not dosed. Intraocular pressure in the untreated controls fluctuated during the study between 17 and 22 mmHg. Intraocular pressure decreased in 3 of 4 BA6650 treated dogs from an initial mean value of 17 to a final mean value of 8 mmHg. Ocular lesions consisting of conjunctival hyperemia, corneal opacities, epiphora, mydriasis followed by miosis, corneal herniation, hypopyon, ptosis, and anterior synechia developed in three of the animals.


Iron overload by transferrin receptor protein 1 regulation plays an important role in palmitate-induced insulin resistance in human skeletal muscle cells.
Free fatty acid is considered to be one of the major pathogenic factors of inducing insulin resistance. The association between iron disturbances and insulin resistance has recently begun to receive a lot of attention. Although skeletal muscles are a major tissue for iron utilization and storage, the role of iron in palmitate (PA)-induced insulin resistance is unknown. We investigated the molecular mechanism underlying iron dysregulation in PA-induced insulin resistance. Interestingly, we found that PA simultaneously increased intracellular iron and induced insulin resistance. The iron chelator deferoxamine dramatically inhibited PA-induced insulin resistance, and iron donors impaired insulin sensitivity by activating JNK. PA up-regulated transferrin receptor 1 (tfR1), an iron uptake protein, which was modulated by iron-responsive element-binding proteins 2. Knockdown of tfR1 and iron-responsive element-binding proteins 2 prevented PA-induced iron uptake and insulin resistance. PA also translocated the tfR1 by stimulating calcium influx, but the calcium chelator, BAPTA-AM, dramatically reduced iron overload by inhibiting tfR1 translocation and ultimately increased insulin sensitivity. Iron overload may play a critical role in PA-induced insulin resistance. Blocking iron overload may thus be a useful strategy for preventing insulin resistance and diabetes.-Cui, R., Choi, S.-E., Kim, T. H., Lee, H. J., Lee, S. J., Kang, Y., Jeon, J. Y., Kim, H. J., Lee, K.-W. Iron overload by transferrin receptor protein 1 regulation plays an important role in palmitate-induced insulin resistance in human skeletal muscle cells.


MRI criteria for multiple sclerosis: Evaluation in a pediatric cohort.
This study assessed the validity of established MRI criteria for multiple sclerosis (MS) in a cohort of 20 children with clinically definite MS. The authors found that many pediatric MS patients did not meet the MRI criteria established for adult-onset MS, particularly the McDonald MRI criteria for dissemination in space. The authors thus suggest that MRI criteria for adult MS be applied cautiously to pediatric MS patients.


Three-year predictive validity of DSM-IV attention deficit hyperactivity disorder in children diagnosed at 4-6 years of age.
Predictive validity is a fundamental consideration in evaluating the DSM-IV diagnostic criteria for attention deficit hyperactivity disorder (ADHD), particularly for younger children. The authors conducted four annual assessments of ADHD and functional impairment using multiple informants in 255 probands and matched comparison children who were 4-6 years old in wave 1. Nearly all children who met full criteria for ADHD in wave 1 met full criteria for ADHD over the next 3 years and continued to display marked functional impairment relative to comparison children, even when intelligence, co-occurring psychopathology, and demographic characteristics were controlled. These findings support the validity of the DSM-IV diagnosis of ADHD in younger children by demonstrating that the symptoms and associated impairment are likely to persist well into elementary school.


Contribution of the MexXY multidrug efflux pump and other chromosomal mechanisms on aminoglycoside resistance in Pseudomonas aeruginosa isolates from canine and feline infections.
As study of multidrug efflux pumps is a crucial step for development of efflux pump inhibitors for treatment of Pseudomonas aeruginosa infection, the objective of this study was to examine the contribution of the MexXY multidrug efflux systems and other chromosomal mechanisms in aminoglycoside (AMG) resistance in P. aeruginosa isolated from dogs and cats. Thirteen Pseudomonas aeruginosa isolates from canine and feline infections were examined for contribution of the MexXY multidrug efflux pump and four other chromosomally-encoded genes including PA5471, galU, nuoG and rplY to AMG resistance. All the isolates were resistant to multiple AMGs and expressed mexXY. Deletion of mexXY caused 2- to 16-fold reduction in AMG MICs. Overproduction of MexXY did not fully account for the observed AMG resistance. No good correlations were detected between MexXY transcription level and AMG MICs. While no mutations were found in mexZ, PA5471 expression varied and its impact on MexXY expression and AMG resistance is diverse. No mutations were found in galU. Only two isolates carried a single base change G-367-T in rplY. Complete transcription of nuoG was detected in all the isolates. In conclusion, the MexXY multidrug efflux pump plays a role in AMG resistance in the dog and cat P. aeruginosa isolates, while disruption of nuoG, rplY and galU did not have a significant impact. These results indicate the existence of uncharacterized AMG-resistance mechanisms.


THE GENETIC ARCHITECTURE OF PLASTICITY TO DENSITY IN IMPATIENS CAPENSIS.
Plant responses to crowding may be mediated by resource availability and/or by a specific environmental cue, the ratio of red:far red wavelengths (R:FR) perceived by phytochrome. This study examined the contribution of phytochrome-mediated photomorphogenesis to genetic variation in plastic responses to density in the annual plant Impatiens capensis. Inbred lines derived from open and woodland populations were grown under low density high density, and high density with selective removal of FR wavelengths to block phytochrome-mediated perception of neighbor proximity. Genetic variation in plasticity to density and to the R:FR cue was detected for several traits Plants grown at high density displayed increased internode elongation; decreased branch, flower, and node production; increased menstem dormancy; and decreased leaf area and specific leaf weight compared to plants grown at low density. Stem elongation responses to density were suppressed when phytochrome perception was blocked at high density. For these phytochrome-mediated traits, a genotype's plasticity to density was strongly correlated with its response to R:FR. Phytochrome-mediated traits were tightly correlated with one another, regardless of the density environment. However, the responses to density of meristem allocation to branching and leaf traits were less strongly phytochrome-mediated. These traits differed in patterns of plasticity, and their genetic correlations often differed across environments. In particular, genetic trade-offs involving meristem allocation to branching were expressed only at low density. The observed density dependence of phenotypic and genetic correlations implies that indirect selection and the potential for correlated response to selection will depend upon the competitive environment. Thus the differential sensitivity of characters to the R:FR cue can influence the evolution of integrated plastic responses to density.


Psychiatric education at the crossroads: issues and future directions.
Psychiatric education is currently facing many critical issues. Their resolution will determine the future availability of psychiatrists and is dependent on the development of new strategies that will require a reorientation in several aspects of current psychiatric education. This may be necessary if the vitality of psychiatry as a specialized branch of medicine is to be maintained and the relevance of psychiatric training and practice to service needs and research objectives is to be increased.


Changes in mental health financing since 1971: implications for policymakers and patients.
The aggregate share that total mental health spending claims of national income has been stable over the past thirty-five years. This stability is a consequence of immense change--new organizational technologies, new treatment technologies, and a growing supply of providers. Aggregate spending stability has been accompanied by major shifts in the composition of financing, which have tended to spread the costs of mental illness more broadly but also have led to fragmentation in public responsibility for people with mental illnesses. Recent developments suggest that financing could be further constrained in the future, even as fragmentation continues to increase.


Bronchopulmonary obstruction in children with respiratory virus infections.
Among 873 children hospitalized with confirmed respiratory viral infections, 492 suffered from bronchopulmonary obstruction. Respiratory syncytial virus infections were dominant among the patients with bronchopulmonary obstruction (80%). The majority of patients with rhinovirus infections suffered from bronchopulmonary obstruction (57%). Two main groups of children at risk from developing bronchopulmonary obstruction during respiratory virus infections were found: 1) infants, suffering from bronchiolitis, mainly due to respiratory syncytial virus, and 2) children of all ages with bronchial asthma, among whom acute attacks were precipitated by virus infections, mainly rhinovirus and respiratory syncytial virus infections. The pathogenesis of bronchopulmonary obstruction during respiratory virus infections is discussed.


Bedside ultrasound measurement of skeletal muscle.
Skeletal muscle and lean body mass may be vital to prognosis and functional recovery in chronic and acute illness, particularly in conditions in which muscle atrophy is prevalent. Ultrasound provides a precise and expedient method to measure muscle mass and changes in skeletal muscle at the bedside. Here, we describe the various methodological approaches along with the validation and reliability tests that have been performed in various populations. Current applications of ultrasound in chronic and acute illness as well as its limitations and strengths in quantifying the muscle mass and changes in muscle over time are discussed. To capitalize on the beneficial features of ultrasound for measuring muscle, we describe the work that is needed to optimize the usefulness of ultrasound in chronic disease and acute care. Given the precision, practicality, and ease of use, ultrasound is emerging as a highly useful tool in expediently measuring the muscle mass and changes in muscle tissue at the bedside. Ultrasound may be valuable in identifying patients who are at risk of malnutrition, in tracking muscle atrophy for the purpose of calculating nutrient delivery, and in assessing the success or failure of nutrition, pharmacological and rehabilitative interventions that aim to counter muscle atrophy.


Click characteristics of northern bottlenose whales (Hyperoodon ampullatus) and Sowerby's beaked whales (Mesoplodon bidens) off eastern Canada.
Passive acoustic monitoring (PAM) is crucial to expanding the knowledge of beaked whales, including the northern bottlenose whale (Hyperoodon ampullatus) and Sowerby's beaked whale (Mesoplodon bidens). Existing descriptions of clicks produced by these species are limited by sample size, number of individuals recorded, and geographic scope. Data from multiple encounters in the western North Atlantic are used to provide a quantitative description of clicks produced by these species. Recordings from nine encounters with northern bottlenose whales in Nova Scotia and Newfoundland were analyzed (N = 2239 clicks). The click type described had a median peak frequency of 25.9 kHz (10th-90th percentile range: 22.9-29.3 kHz), and a median inter-click interval (ICI) of 402 ms (N = 1917, 10th-90th percentile range: 290-524 ms). Recordings from 18 Sowerby's beaked whale encounters from Nova Scotia were analyzed (N = 762 clicks). The click type described had a median peak frequency of 65.8 kHz (10th-90th percentile range: 61.5-76.5 kHz), and a median ICI of 237 ms (N = 677, 10th-90th percentile range: 130-315 ms). These results will contribute to the development of methods to detect and classify beaked whale clicks to the species level, improving the effectiveness of PAM and enhancing scientific understanding and conservation efforts for cryptic and at-risk cetaceans.


Atrial natriuretic peptide inhibits cell cycle activity of embryonic cardiac progenitor cells via its NPRA receptor signaling axis.
The biological effects of atrial natriuretic peptide (ANP) are mediated by natriuretic peptide receptors (NPRs), which can either activate guanylyl cyclase (NPRA and NPRB) or inhibit adenylyl cyclase (NPRC) to modulate intracellular cGMP or cAMP, respectively. During cardiac development, ANP serves as an early maker of differentiating atrial and ventricular chamber myocardium. As development proceeds, expression of ANP persists in the atria but declines in the ventricles. Currently, it is not known whether ANP is secreted or the ANP-NPR signaling system plays any active role in the developing ventricles. Thus the primary aims of this study were to 1) examine biological activity of ANP signaling systems in embryonic ventricular myocardium, and 2) determine whether ANP signaling modulates proliferation/differentiation of undifferentiated cardiac progenitor cells (CPCs) and/or cardiomyocytes. Here, we provide evidence that ANP synthesized in embryonic day (E)11.5 ventricular myocytes is actively secreted and processed to its biologically active form. Notably, NPRA and NPRC were detected in E11.5 ventricles and exogenous ANP stimulated production of cGMP in ventricular cell cultures. Furthermore, we showed that exogenous ANP significantly decreased cell number and DNA synthesis of CPCs but not cardiomyocytes and this effect could be reversed by pretreatment with the NPRA receptor-specific inhibitor A71915. ANP treatment also led to a robust increase in nuclear p27 levels in CPCs compared with cardiomyocytes. Collectively, these data provide evidence that in the developing mammalian ventricles ANP plays a local paracrine role in regulating the balance between CPC proliferation and differentiation via NPRA/cGMP-mediated signaling pathways.


[Prognostic factors of prostate cancer treated with first-line hormone therapy].
Endocrine therapy of prostate cancer is designed to eliminate the action of androgens to prevent the growth of hormone-sensitive cancer cells. The duration and quality of the response to this treatment vary from one patient to another. The objective of this study was to evaluate the prognostic factors of patients treated by first-line endocrine therapy for prostate cancer. From September 1988 to September 1999, 170 patients receiving first-line endocrine therapy for prostate cancer were included. Endocrine therapy consisted of LHRH analogues alone in 59.4% of cases, complete androgen suppression in 21.2% of cases, antiandrogens alone in 17.6% of cases and oestrogens in 1.8% of cases. Clinical, laboratory, scintigraphic and histological data were collected. The overall survival was studied by univariate analysis as a function of pretreatment criteria using Kaplan-Meier survival curves. The mean survival of the population was 33 +/- 26 months (range: 2-126 months). The following parameters were associated with a significant reduction of overall survival: age greater than 70 years, high ECOG score, mode of presentation of the cancer by alteration of general state, presence of bone pain, presence of bone metastases particularly in the appendicular skeleton, dilatation of renal cavities, Gleason score > 5, PSA level > 100 ng/ml, haemoglobin < 13.5 g/dl, serum creatinine > 105 mumol/l, low plasma testosterone, high alkaline phosphatase, poor response to treatment assessed by PSA greater than 4 ng/ml at 3, 6 and 12 months. Determination of these prognostic factors can be used to predict the patient's response to endocrine therapy and survival. These factors can also be used to stratify patients in comparable groups for clinical trials.


Correlation between the severity of sleep apnea and upper airway morphology in pediatric and adult patients.
Recent advances in upper airway imaging allow a better analysis of the upper airway morphology. With the increased accuracy of computed tomography, MRI and other imaging techniques, it becomes possible to identify very local changes in bony structure, soft tissues and lumen of the pharyngeal airway. These advances are able to provide new insights into obstructive sleep apnea (OSA) evaluation and treatment. The present review intends to capture the current status of the research on the correlation between OSA severity and upper airway morphology. Morphological abnormalities that are responsible for OSA differ with age. Therefore, correlations between morphology and OSA in children and adults and the effects of puberty are discussed in different chapters. Literature provides several anatomical correlates that correlate with the severity of OSA but are not able to differentiate healthy individuals from OSA patients. As anatomical correlates are not able to identify OSA in an individual, their main importance might lie in the selection of the ideal treatment on a patient-specific basis. Several sources report promising results in this use of morphological biomarkers. These, in combination with the new insights gained by the advances in imaging, should be the bases for additional research in the domain of treatment selection and result prediction.


[Peutz-Jeghers syndrome and cancer:a retrospective study in 14 Japanese patients with Peutz-Jeghers syndrome].
We retrospectively investigated 14 Japanese patients with Peutz-Jeghers (PJ) syndrome who were treated in six hospitals to determine the prevalence of cancer in Japanese patients with PJ syndrome. The study included seven males and seven females. The mean age at the time of diagnosis of PJ syndrome was 28.1 years (range 2-60 years). Hamartomatous polyps were observed in 13 (92.9%) patients, mucocutaneous pigmentation in 11 (78.6%), and positive family history in six patients (42.9%). The mean observation period after the diagnosis of PJ syndrome was 10.1 years (range 0-34 years). Although one patient died of cancer of unknown primary origin, the remaining 13 patients included in the study completed their last follow-up at each hospital. Cancers were detected in six patients (42.9%), including cancer of the uterine cervix (N=3), breast cancer (N=1), duodenal cancer (N=1), transverse colon cancer (N=1), and cancer of unknown primary origin (N=1). One patient presented with both cervical cancer and breast cancer. No patient presented with pancreatic cancer. This study highlights that patients with PJ syndrome are at high risk for intestinal and extra-intestinal cancers, such as uterine and breast cancer. Routine surveillance for intestinal and extra-intestinal malignancies is warranted in patients with PJ syndrome.


Resting metabolic rate in young Polynesian and Caucasian women.
To investigate whether resting metabolic rate (RMR) differs between Caucasian and Polynesian women. Cross-sectional comparison. Eighty-two (42 Caucasian, 40 Polynesian) healthy women aged between 18 and 27 y. RMR (indirect calorimetry) and body composition (fat-free mass and fat mass derived from oxygen-18 dilution measurement of total body water). RMR was similar in the Caucasian (6956 +/- 1291 (s.d.) kJ/d) and Polynesian (7125 +/- 1290 kJ/d) groups while fat-free mass was significantly lower in the Caucasian group (45.3 +/- 6.8 vs 51.0 +/- 6.4 kg, P < 0.002). After adjustment for fat-free mass and fat mass, RMR was lower in the Polynesian than the Caucasian groups (6783 +/- 904 vs 7281 +/- 901 kJ/d, P = 0.023). The significantly lower relative RMR observed in Polynesian compared to Caucasian women may predispose Polynesian women to eventual onset of obesity.


Ginger essential oil-based microencapsulation as an efficient delivery system for the improvement of Jujube (Ziziphus jujuba Mill.) fruit quality.
Microencapsulation of Zingiber officinale essential oil (EO) in polysaccharide, chitosan (CH) and sodium carboxymethyl cellulose (CMC) based on the electrostatic interaction between charged polysaccharides at pH 3.0 in dual delivery system. Ratio variations of CH and CMC in microencapsulation were studied at 1:2, 2:1 and 1:1. This study aimed to evaluate the influence of the encapsulating materials combination on freeze-dried EO powders and to present the mechanisms for loading and releasing EO involved in the preparation of CH/CMC microcapsules. The spectroscopy analysis, physical properties, microstructural, encapsulation efficiency and EO release behavior in obtained EO microparticles were evaluated by using the analysis of fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and gas chromatography mass spectrometry (GC-MS), respectively. Afterwards, the above prepared microcapsules were applied on winter jujube fruit (Ziziphus jujuba Mill.) preservation. Results demonstrated that both the microstructure and stability of microencapsulation were improved in delivery system loading with CH and CMC (1:1) with the encapsulation efficiency of 88.50%, compared to other ratios of CH and CMC (1:2 and 2:1). Furthermore, the microencapsulation had a capacity to control and reduce the EO release, therefore the morphological and sensory quality of jujube fruits in EO delivery system during storage was enhanced significantly (P < 0.05), in comparison to control. Results revealed that the microparticles produced with CH and CMC (1:1) was considered to present better characteristics of microstructure, encapsulation efficiency, as well as to maintain higher nutritional quality for jujube fruit. Thus, EO microencapsulation loaded in CH/CMC-based dual delivery system has potential application and developmental value prospects in food industries.


Kingella kingae endophthalmitis in an infant.
An 11-month-old girl presented with metastatic endophthalmitis. The causative organism was the Gram-negative coccobacillus Kingella kingae. This is an uncommon organism first recognised in 1967. It has never been previously reported to cause endophthalmitis, but is associated with at least four other infective syndromes in children. Endophthalmitis is a potentially lethal and sight-threatening disease. Kingella kingae is primarily a paediatric pathogen which fortunately responds well to antibiotics. A case study, details of the bacteriology and a table of other clinical syndromes associated with this organism seen at our institution constitute this article. (12 references).


Amino acid sequence of rabbit carbonic anhydrase II.
The amino acid sequence of the high activity form of erythrocyte carbonic anhydrase, carbonic anhydrase II, purified from rabbit erythrocytes has been determined. This sequence was determined primarily from the cyanogen bromide and tryptic peptides through use of automated Edman degradation procedures. The ordering of the peptides from rabbit carbonic anhydrase II was based on the high degree of homology between the rabbit enzyme and the homologous enzymes derived from sheep, bovine, and human erythrocytes. The function of certain residues is discussed in the context of these three known sequences and the previously reported three-dimensional structure of human carbonic anhydrase II. Possible microheterogeneity of rabbit carbonic anhydrase II is also discussed.


Tension required for pectate chemistry to control growth in Chara corallina.
Recent work showed that polygalacturonate (pectate) chemistry controlled the growth rate of the large-celled alga Chara corallina when turgor pressure (P) was normal (about 0.5 MPa). The mechanism involved calcium withdrawal from the wall by newly supplied pectate acting as a chelator. But P itself can affect growth rate. Therefore, pectate chemistry was investigated at various P. A pressure probe varied P in isolated walls, varying the tension on the calcium pectate cross-links bearing the load of P. When soluble pectate was newly supplied, the wall grew irreversibly but the pectate was inactive below a P of 0.2 MPa, indicating that tension was required in the existing wall before new pectate acted. It was suggested that the tension distorted some of the wall pectate (the dominant pectin), weakening its calcium cross-links and causing the calcium to be preferentially lost to the new pectate, which was not distorted. The preferential loss provided a molecular mechanism for loosening the wall structure, resulting in faster growth. However, the resulting relaxation of the vacated wall pectate would cause calcium to be exchanged with load-bearing calcium pectate nearby, auto-propagating throughout the wall for long periods. There is evidence for this effect in isolated walls. In live cells, there is also evidence that auto-propagation is controlled by binding the newly supplied pectate (now calcium pectate) to the wall and/or by additional Ca(2+) entering the wall structure. A tension-dependent cycle of pectate chemistry thus appeared to control growth while new wall was deposited as a consequence.


Human foetal measurements between 50 and 150 days of gestation, in relation to crown-heel length.
Weights and a number of linear measurements were related to crown-heel length in fresh apparently normal foetuses ranging from 8 to 21 weeks' post-menstrual age. The average relationships agreed remarkably well with results reported many years ago on the basis of preserved specimens mostly from spontaneous abortions. There was no evidence of sex differences.


Specific conductance and ionic characteristics of farm canals in the everglades agricultural area.
Specific conductance in farm canals of the Everglades Agricultural Area (EAA) in south Florida is an important water quality parameter that was categorized as a parameter of concern according to an observed frequency of >5% excursions over the Class III water quality criterion and needed to be addressed as a part of the Everglades Regulatory Program. This study was conducted to evaluate specific conductance in farm canals of the EAA. Specific conductance was monitored at 10 representative farms (a total of 12 pump stations) in the EAA using multi-parameter water quality data loggers, for periods ranging from 24 to 83 mo. Cation and anion concentrations were also determined. Nonparametric Mann-Kendall trend analyses and Sen's slope analysis of specific conductance were conducted to determine specific conductance trends. Mean specific conductance ranged from 0.74 to 1.68 dS m(-1) and only 2 of the 10 farms were above the State Class III water quality criterion of 1.275 dS m(-1). Statistically significant downward trends were observed at 3 of the 10 farms. Determination of ion compositions in grab samples at 8 of the 10 farms indicated that the major ions contributing to the increase in specific conductance in the EAA were Cl-, HCO3-, and Na+. Mean Na/Cl ratios in most of the EAA canals ranged from 0.57 to 0.78, whereas those of SO4/Cl ranged from 0.46 to 0.98. Investigation of historical data and literature indicates that elevated specific conductance in parts of the EAA is a natural phenomenon due to entrapment of connate seawater in the Everglades formation. Sulfur contributes minor increases in specific conductance in the EAA with probable sources from organic soil mineralization, ground water, Lake Okeechobee, and S fertilizers.


Bacillus Calmette-Guérin interacts with the carboxyl-terminal heparin binding domain of fibronectin: implications for BCG-mediated antitumor activity.
Intravesical bacillus Calmette-Guérin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma of the bladder. The mechanisms by which BCG achieves this effect remain unclear. Reports have attributed an important role to fibronectin both in the initial attachment of BCG to bladder surfaces and in the limitation of tumor cell motility. In the present study, using limited protease cathepsin B degradation followed by Western blot analyses with antibodies to various domains of the fibronectin molecule, we showed that BCG appears to bind to fibronectin near the carboxyl terminal and adjacent to the heparin binding domain. Furthermore a 51-chromium release assay with human bladder cancer cell line T24 as target cells and lymphokine activated killer (LAK) cells as effector cells showed that fibronectin was needed for tumor cytotoxicity by the LAK cells. By using antibodies and peptides to various domains of the fibronectin molecule, the heparin binding domain, but not the cell binding domain, carboxyl terminal region, or the amino terminal region of the fibronectin molecule, was identified as essential to tumor cell lysis by the LAK cells. Flow cytometric analysis showed that both peripheral blood lymphocytes and the LAK cells express fibronectin receptors VLA-3, VLA-4 and VLA-5 on their surfaces. However, the numbers of receptors are not significantly different in the two cell populations. We conclude that, by binding near the carboxyl terminal region and adjacent to the heparin-binding domain of the fibronectin molecule, BCG may protect this region of the molecule from tumor proteases, and may thus allow the antitumor activity of the host immune cells to take place.


[CA 125 kinetic pattern during chemotherapy].
CA 125 is a tumoral marker that may be elevated in non-mucinous epithelial ovarian tumours but is neither sensitive nor specific enough to be used as a diagnostic tool. However, CA 125 serum concentration variations can be used for monitoring chemotherapy efficiency. This study concerns 75 patients who underwent surgical cytoreduction followed by a first-line chemotherapy during which CA 125 serum variations were studied by calculation of mono-exponential regression curve slopes and half-lives. Persistence of tumour residues was evaluated by tomodensitometry and/or second look surgery du- ring a post-chemotherapy check-up. A slope > - 0,0156 (half-life > 44,43 d) was a perfect predictor of a persistent tumour; conversely, a slope < - 0,0340 (half-life < 20,39 d) reliably predicted the absence of detectable tumour. We propose a personalised graphic representation of CA 125 variations to follow-up chemotherapy. Its exploitation, in association with classical prognostic factors, could improve patients monitoring.


Hardware failures in spinal cord stimulation (SCS) for chronic benign pain of spinal origin.
Spinal cord stimulation (SCS) has become an established clinical option for treatment of refractory chronic pain not related to cancer. Current hardware and implantation techniques for SCS are already highly developed and continuously improving, however equipment failures over the course of the long-term treatment are still encountered in a relatively high proportion of treated cases. Percutaneous SCS electrodes seem to be particularly prone to dislocation and insulation failures. This review summarizes the experience of the authors with management of hardware failures and their causes in patients treated with SCS for chronic pain of benign origin. The published literature is critically surveyed and discussed.


Effect of compressive force on the production of prostaglandin E(2) and its receptors in osteoblastic Saos-2 cells.
In orthodontic tooth movement, prostaglandin E(2) (PGE(2)) released from osteoblasts can alter the normal process of bone remodeling. We examined the effect of compressive force (CF) on PGE(2) production, PGE receptors (Ep1-4) expression, phosphorylation of protein kinase A (p-PKA), and calcium content in Saos-2 cells. PGE(2) production increased as CF strength. Applying CF of 98 or 294 Pa caused the cells to produce approximately 700 and 1,400 pg/mL PGE(2), respectively. CF of 98 Pa increased Ep2 gene expression, and 98 and 294 Pa CF increased Ep4. Immunohistochemical staining showed strong expression of Ep2 under 98 Pa and Ep4 under 98 and 294 Pa. The p-PKA increased as the strength of CF or PGE(2) concentration. The calcium content was increased by the addition of 700 pg/mL PGE(2) but was decreased by 1400 pg/mL. Thus, mechanical stress controls bone formation by stimulating PGE(2) production and Ep2 and/or Ep4 expression in osteoblasts.


[Hi-tech trends in future dentistry--part A: computerized technologies].
Growing knowledge and information in the field of dentistry has had a great impact on dental education, management and practice. A prominent change is the digital revolution, which presents new computed technologies and accessible means of communication for sharing written and visual information. Biotechnology, yet another innovated field, will change dentistry even further. This article presents dental innovations forwarded by Israeli Hi-Tech companies. An overview of some advances in technology in the field of dentistry is presented. Part of the described technologies is in R&D phase, part is under preliminary clinical evaluation, and a few have undergone short-term clinical studies. Part A of the article discusses the application of computerized imaging systems to educational purposes, diagnostics and treatment; part B presents other diagnostic and therapeutic technologies.


[Causes and diagnostic criteria of hepatic coma--an analysis of 560 cases].
560 patients with hepatic coma were treated during the years 1958 to 1982 in Homburg and Bad Kissingen . 82 patients had an endogeneous and 478 an exogeneous hepatic coma. Endogeneous hepatic coma was caused most frequently by fulminant virus hepatitis, intoxication, and hepatorenal syndrome accompanying serum hepatitis. Exogeneous hepatic coma in patients with cirrhosis of the liver was caused in most cases by gastrointestinal bleeding, by a diet too high in protein, or by excessive diuresis. Early clinical symptoms are changes in writing tests and ability to concentrate, whereas hepatic foetor occurs in coma stage III and IV. Clinical chemistry findings pointing to imminent hepatic coma are increase of arterial ammonia in exogeneous hepatic coma, and increase of free phenols in endogeneous hepatic coma. The increase of prothrombin time is prognostic for imminent hepatic coma in both types. Prognosis of endogeneous hepatic coma is still rather bad; 87% of the patients suffering from it died; in exogeneous hepatic coma prognosis has improved for stage I and II in the last 23 years, whereas however the total prognosis for all 4 stages is still unchanged, letality being 55%.


Recognition memory for typical and unusual faces.
In four studies, recognition memory for faces rated as similar to a prototype was found to be inferior to memory for faces rated as unusual in appearance. This result was obtained under both incidental and intentional learning conditions, at presentation rates ranging from 3 to 15 sec, and with retention intervals from 3 to 24 hr. A fifth experiment established interitem similarity as the structural basis of this typicality effect in recognition memory. Difficulties in interpreting the findings in terms of some current models for classification learning, depth of processing models, or present models of the word frequency effect are discussed.


Accumulation of CD69+ tissue‑resident memory T cells in the nasal polyps of patients with chronic rhinosinusitis.
In patients with chronic rhinosinusitis with nasal polyps (CRSwNP), a relative accumulation of cluster of differentiation (CD)8+ T cells over CD4+ T cells occurs in nasal polyps compared with the peripheral blood. Nasal CD8+ T cells and CD4+ T cells predominantly present an effector memory phenotype. Immunological studies have reported that memory T cells recirculate from the tissues to the peripheral blood and a high percentage of these T cells persist within the tissue. The aim of the present study was to characterize CD69+ sphingosine‑1‑phosphate receptor 1 (S1PR1)‑ tissue resident memory T cells (Trm) in the polyps of patients with CRSwNP. Tissue and blood samples were collected from 10 patients undergoing nasal sinus surgery. Expression of specific extra‑ and intracellular molecules were analyzed using multicolor flow cytometry. A significantly higher level of CD8+ T cells than CD4+ T cells was present in nasal polyps, while significantly more CD4+ T cells than CD8+ T cells were detected in the peripheral blood of patients with CRSwNP. The frequency of CD69+ T cells was significantly higher in CD8+ and CD4+ T cells in nasal polyps compared with the peripheral blood. The frequency of CD69+ S1PR1‑ Trm was also significantly higher in CD4+ and CD8+ T cells from nasal polyps compared with the peripheral blood. Within polyps, the frequency of CD69+ S1PR1‑ Trm was again significantly higher in CD8+ compared with CD4+ T cells. In summary, a significantly higher frequency of CD69+ S1PR1‑ T cells was observed in the nasal polyps compared with the peripheral blood in patients with CRSwNP. The results of the present study suggest that local regulation of the immune response occurs within nasal polyps. As such, Trm should be considered a potential stimulus in the pathogenesis of nasal polyps. However, the role of Trm in nasal polyps as a pathogenic trigger of the local inflammatory reaction requires further investigation.


Experimental Characterization of the Binding Affinities between Proapoptotic BH3 Peptides and Antiapoptotic Bcl-2 Proteins.
The Bcl-2 family proteins are key regulators of the intrinsic apoptotic pathway and are among the validated targets for developing anticancer drugs. Protein-protein interactions between the pro- and antiapoptotic members of this family determine mitochondrial outer-membrane permeabilization. Elucidating such protein-protein interactions in a quantitative way is helpful for network pharmacology studies on the Bcl-2 family, which, in turn, will provide valuable guidance for developing new anticancer therapies. In this study, the binding affinities of the BH3 peptides derived from eight proapoptotic BH3-only proteins (i.e., Bid, Bim, Puma, Noxa, Bad, Bmf, Bik, Hrk) against five well-studied antiapoptotic proteins (i.e., Bcl-xL , Bcl-2, Mcl-1, Bcl-w, Bfl-1) in the Bcl-2 family have been measured. Three different types of binding assay (i.e., surface plasmon resonance, fluorescence polarization, and homogeneous time-resolved fluorescence) were employed for cross-validation. The results confirmed that each proapoptotic BH3 peptide exhibited a distinct binding profile against the five antiapoptotic proteins. The binding data obtained herein serve as a fresh update or correction to existing knowledge. It is expected that such binding data will be helpful for building more accurate mathematical network models for depicting the complex protein-protein interactions within the Bcl-2 family.


Is there a natural limit of the transformation rate of oral leukoplakia?
Recent reviews described a cumulative risk of 0-38% of oral leukoplakias (OL) to transform into oral squamous cell carcinoma (OSCC). The annual transformation rate (ATR) of OL into OSCC amounted up to 6.3%. To elucidate epidemiological consequences of varying ATR. Variations of the prevalence (1-2%) and ATR (0.5-4%) of OL were used to compute the proportional incidences of OSCC developing in OL. These were compared to the actual incidences of OSCC excerpted from European cancer registries. A ratio <50% of predicted to actual incidence overall indicated a plausible ATR. With an ATR>or=3%, the predicted incidences of OSCC would exceed the reported incidences in all countries. With an ATR<or=1%, the ratio of OSCC developed in OL to OSCC overall would be always lower than 50%. Based on present data, it was concluded that the ATR of OL into OSCC should not exceed 1%.


Genetic correlations between pain phenotypes and depression and neuroticism.
Correlations between pain phenotypes and psychiatric traits such as depression and the personality trait of neuroticism are not fully understood. In this study, we estimated the genetic correlations of eight pain phenotypes (defined by the UK Biobank, n = 151,922-226,683) with depressive symptoms, major depressive disorders and neuroticism using the the cross-trait linkage disequilibrium score regression (LDSC) method integrated in the LD Hub. We also used the LDSC software to calculate the genetic correlations among pain phenotypes. All pain phenotypes, except hip pain and knee pain, had significant and positive genetic correlations with depressive symptoms, major depressive disorders and neuroticism. All pain phenotypes were heritable, with pain all over the body showing the highest heritability (h2 = 0.31, standard error = 0.072). Many pain phenotypes had positive and significant genetic correlations with each other indicating shared genetic mechanisms. Our results suggest that pain, neuroticism and depression share partially overlapping genetic risk factors.


Influence of Density on Interspecific Competition Between Spathius galinae (Hymenoptera: Braconidae) and Tetrastichus planipennisi (Hymenoptera: Eulophidae), Larval Parasitoids of the Invasive Emerald Ash Borer (Coleoptera: Buprestidae).
The outcomes of interspecific interactions between parasitoids depend on a variety of factors. Understanding the influence of these factors is important for classical biological control, where the success of parasitoid releases partly depends on interactions with native and other introduced species. However, results from laboratory experiments may not always reflect those in the field, as densities may be artificially inflated. To mitigate this problem, we examined the effects of multiple densities on interspecific competition between two larval parasitoids of emerald ash borer (Agrilus planipennis Fairmaire): Spathius galinae Belokobylskij and Tetrastichus planipennisi Yang. Parasitoid species were housed individually or together at two different densities, and we measured the effects on percent parasitism and progeny production, before calculating the interaction strengths. We found no significant effects of parasitoid density on percent parasitism, but the effect of competition on parasitism generally was reduced at lower densities. However, there were significant differences in parasitism by species, with S. galinae parasitizing more larvae than T. planipennisi. There were also no significant effects of parasitoid density on the number of progeny produced by each species, though the effect of competition on progeny production was greater at higher densities. Similarly, though, there were significant differences between species in the number of progeny produced. Specifically, T. planipennisi consistently produced larger broods than S. galinae. Our findings complement existing research suggesting that competition between these two species in the field will likely be negligible.


Aggregates of mutant protein appear progressively in dendrites, in periaxonal processes of oligodendrocytes, and in neuronal and astrocytic perikarya of mice expressing the SOD1(G93A) mutation of familial amyotrophic lateral sclerosis.
Mice expressing the G93A and other mutations of Cu,Zn superoxide dismutase (SOD1(G93A)) are valid models for the familial form of amyotrophic lateral sclerosis (FALS) with SOD1 mutations and, probably, for sporadic ALS. Adult mice become progressively paralyzed and show most of the histopathological lesions reported in sporadic ALS, i.e. neuronal loss, astrogliosis, ubiquitin and Lewy body-like inclusions, dystrophic axons and fragmentation of the Golgi apparatus (GA) of motor neurons. In transgenic mice, the mutant protein and ubiquitin aggregate within pathological 13 nm thick filaments [Stieber A, Gonatas JO, Gonatas NK. J Neurol Sci 2000;173:53-62]. This immunocytochemical and quantitative study of mice expressing SOD1(G93A) establishes the chronological order and cellular localization of aggregates of SOD1 and their correlation with fragmentation of the GA. Young asymptomatic mice expressing SOD1(G93A) showed aggregates of mutant SOD1 within neurites, prior to the detection of SOD1 in the perikarya of spinal cord motor neurons and astrocytes. Both dendrites and the periaxonal oligodendroglial cytoplasm, surrounding atrophic axons, contained SOD1 as revealed by immunoelectron microscopy The perikarya of a small percentage of spinal cord motor neurons contained both fragmented GA and aggregates of SOD1; however, about 50% of motor neurons with fragmented GA did not contain SOD1 in the perikaryon, suggesting that aggregates of mutant protein may not directly cause fragmentation of the GA. The mechanism of the putative toxic effect by the mutant protein remains to be clarified. The isolation and biochemical characterization of the filamentous aggregates of mutant protein and ubiquitin from spinal cords of transgenic mice expressing mutations of the SOD1 gene may offer clues on pathogenetic mechanisms.


Health Insurance Coverage of Gender-Affirming Top Surgery in the United States.
Despite the medical necessity, legislative mandates, and economic benefits of gender-affirming surgery, access to treatment remains limited. The World Professional Association for Transgender Health (WPATH) has proposed guidelines for transition-related surgery in conjunction with criteria to delineate medical necessity. The authors assessed insurance coverage of "top" gender-affirming surgery and evaluated the differences between insurance policy criteria and WPATH recommendations. The authors conducted a cross-sectional analysis of insurance policies for coverage of top gender-affirming surgery. Insurance companies were selected based on their state enrollment data and market share. A Web-based search and individual telephone interviews were conducted to identify the policy. Medical necessity criteria were abstracted from publicly available policies. Of the 57 insurers evaluated, bilateral mastectomy (transmasculine) was covered by significantly more insurers than breast augmentation (transfeminine) (96 percent versus 68 percent; p < 0.0001). Only 4 percent of companies used WPATH-consistent criteria. No criterion was universally required by insurers. Additional prerequisites for coverage that extended beyond WPATH guidelines for top surgery were continuous living in congruent gender role, two referring mental health professionals, and hormone therapy before surgery. Hormone therapy was required in a significantly higher proportion of transfeminine policies compared with transmasculine policies (90 percent versus 21 percent; p < 0.0001). In addition to the marked intercompany variation in criteria for insurance coverage that often deviated from WPATH recommendations, there are health care insurers who categorically deny access to top gender-affirming surgery. A greater evidence base is needed to provide further support for the medical necessity criteria in current use.


Color image phase conjugation in photorefractive crystal Fe:LiNbO(3).
This paper reports a color phase conjugation demonstration in photorefractive crystal iron doped lithium niobate. Two color lasers are used with wavelengths of 4880 and 6328 A. We obtain a color phase conjugation wave. Distortion correction of the color image is done in the experiment. Weak coupling between the two color laser waves is discovered.


Management of undescended testis: a decision analysis.
Undescended testis (UDT) or cryptorchidism is the most common genital anomaly seen in boys and can be treated surgically by orchidopexy. The age at which orchidopexy should be performed is controversial for both congenital and acquired UDT. A decision analysis is performed in which all available knowledge is combined to assess the outcomes of orchidopexy at different ages. Without surgery, unilateral congenital UDT and bilateral congenital UDT are associated with average losses in quality-adjusted life-years (QALYs) of 1.53 QALYs (3% discounting 0.66 QALYs) and 5.23 QALYs (1.91 QALYs), respectively. Surgery reduces this QALY loss to on average 0.84 QALYs (0.21 QALYs) for unilateral UDT and 1.66 QALYs (0.40 QALYs) for bilateral UDT. Surgery at detection will lead to the lowest QALY loss of 0.91 (0.34) and 1.73 (0.60) QALYs, respectively, for unilateral and bilateral acquired UDT compared with surgery during puberty and no surgery. No sensitivity analysis is able to change the preferences for these strategies. Based on our decision analytic model using societal valuations of health outcomes, surgery for unilateral UDT (both congenital and acquired) yielded the lowest loss in QALYs. Given the modest differences in outcomes, there is room for patient (or parent) preference with respect to the performance and timing of surgery in case of unilateral UDT. For bilateral UDT (both congenital and acquired), orchidopexy at any age provides considerable benefit, in particular through improved fertility. As there is no strong effect of timing, the age at which orchidopexy is performed should be discussed with the parents and the patient. More clinical evidence on issues related to timing may in the future modify these results and hence this advice.


Distinct histological features characterize primary angiosarcoma of bone.
To define the histological criteria of primary angiosarcoma of bone. Forty-two angiosarcomas of bone in 23 males and 15 females were studied. Histological criteria were related to patients' outcome. Eleven patients had multifocal lesions. Lesions were located in the long and short tubular bones followed by the pelvis, spine and trunk. Tumour cells were positive for CD31 in 38 of 40, von Willebrand Factor in 21 of 35, CD34 in 15 of 38, smooth muscle actin in 22 of 36, D2-40 in 11 of 35 and keratin AE1AE3 in 27 of 39. Thirty-nine tumours showed an epithelioid phenotype. One- and 5-year survival rates were 55% and 33%, respectively. Survival analysis showed that a macronucleolus, three or more mitoses per 10 high-power field (HPF) and fewer than five eosinophilic granulocytes per 10 HPF within a tumour was associated with an even worse survival compared to the overall group. Because keratin positivity is seen in the majority of cases, pathologists should avoid misinterpretation as metastatic carcinoma. A macronucleolus, three or more mitoses per 10 HPF and fewer than five eosinophilic granulocytes per 10 HPF can be used to further define angiosarcoma of bone.


Microvascular density and vascular endothelial growth factor have little correlation with prognosis of craniopharyngioma.
Craniopharyngioma is histologically a benign epithelial tumor located in the supersellar cistern that often presents aggressive growth and repeated recurrence. The authors hypothesized that craniopharyngioma recurrence and invasive growth are angiogenesis dependent and evaluated the significance of vascularization in the prognosis of craniopharyngioma by a prospective cohort study. The cohorts consisted of 32 patients with AE and 31 patients with SP tumor. The primary and recurrence removal specimens of the cohort patients were gathered. Microvascular density and VEGF protein in the recurrence group and recurrence-free group were detected by the immunohistochemistry avidin-biotin-peroxidase method and analyzed quantitatively through computer-assisted microscopy to evaluate the correlation of MVD and VEGF with prognosis of craniopharyngiomas. The average follow-up phase was 63.34 months; 14 of 32 patients with AE and 6 of 31 patients with SP had recurrence and underwent operation again. Although MVD and VEGF have significant difference between AE and SP (P=.000, P=.018, respectively), MVD and VEGF have no statistical difference between the recurrence group and recurrence-free group (P>.05). Microvascular density and VEGF in craniopharyngioma tissue have no correlation with prognosis of the tumor, which may be explained by the minimal blood circulation in the craniopharyngioma. Adamantine epithelioma showed more tendency to recur than SP.


New tuberculosis therapeutics: a growing pipeline.
Novel chemotherapeutic drugs are needed to improve tuberculosis (TB) control, especially in the developing world. Given the magnitude of the problem and the resources available in countries that have the highest burden of disease, the present standards of care for the treatment of drug-susceptible TB, drug-resistant TB, TB/human immunodeficiency virus (HIV) coinfection, and latent TB infection are all unsatisfactory. Because no truly novel compounds for the treatment of TB have been discovered in the past 40 years, the recent enhanced activity in the research and development of new TB drugs is extremely encouraging. Seven compounds are presently in clinical development specifically for the treatment of TB. Other known antibiotic compound families are being investigated preclinically, in an attempt to identify new antimicrobial drugs with specific antituberculous activity. In addition, novel targets have been identified and are the subject of efforts to validate their potential usefulness in the treatment of TB.


[Cancer treatment by comprehensive regulation of anti-tumor immune network].
Anti-tumor effects of current cancer vaccines are limited. However, detailed analyses of clinical trials revealed several important points to be improved towards immunological tumor rejection. These are, (1) identification of tumor antigens involved in tumor cell proliferation/survival and expressed in cancer stem cells, (2) development of in situ tumor destruction methods which release tumor antigens in an immunogenic manner to induce immune responses to multiple endogenous tumor antigens, (3) development of methods to augment antigen processing and presentation by dendritic cells, including effective adjuvants, (4) development of methods to expand CTL and helper T cells in vivo, (5) understanding of mechanisms underlying cancer induced immunosuppression and development of methods to overcome them. Comprehensive interventions on these points in the antitumor immune network will lead to effective cancer immunotherapy.


Dry eye disease in chronic graft-versus-host disease: results from a Spanish retrospective cohort study.
We describe the incidence, clinical features, and final outcome of dry eye disease (DED) associated with chronic graft-versus-host disease (GVHD) over a 5-year period. We reviewed 109 clinical charts from patients undergoing hematopoietic stem cell transplantation (HSCT) between January 2000 and December 2005, abstracting data from the 57 patients who developed chronic GVHD and survived at least 180 days after allogenic HSCT. DED occurred in 22 (40%) patients at an average of 16.5 months after HSCT. Photophobia, irritation, and foreign body sensation were the most frequent symptoms, while punctate keratitis was the most common sign. DED tended to improve over time, with fewer than 5% of patients requiring more than two topical medications at the end of follow-up. Our study represented a formal evaluation of DED incidence among Spanish chronic GVHD patients. It is of utmost importance to assure patients will undergo a comprehensive ophthalmologic evaluation throughout their follow-up.


[A case of pleomorphic liposarcoma originating from mesentery].
Liposarcoma is one of the most common soft tissue sarcomas that occurs in adults and is currently divided into five main subgroups: well-differentiated, myxoid, round cell, pleomorphic, and dedifferentiated. Primary mesenteric liposarcoma is extremely rare, and the treatment strategy is surgical resection with a wide free margin, often followed by radiation and adjuvant chemotherapy if distant metastasis is not detected. A 73-year-old male patient presented with lower abdominal distension. Abdominal CT scan revealed a large homogeneously enhancing mass lesion abutting the sigmoid colon and urinary bladder. At laparotomy, the solid mass measured 28×26×12 cm in size, was well-demarcated, and originated from the mesentery of the middle ileum. It was removed along with some small intestine (ileocecal valve upper 50-150 cm) and ileal mesentery because of adhesion. Histologically, the tumor proved to be pleomorphic liposarcoma. The patient did not undergo any adjuvant treatment following surgery, but he remains disease free until 33 months after surgery. Herein, we report a case of pleomorphic liposarcoma arising from small bowel mesentery.


Objective correlates of an unusual subjective experience: A single-case study of number-form synaesthesia.
There is a universal and often unconscious tendency to mentally associate the number sequence with a spatial continuum (the mental number line). Here we study one individual who reports a strong and vivid sense of space when processing numbers. For him, the number sequence has a precise spatial form: a curvilinear right-to-left oriented line. We used various tasks to demonstrate that this numerical-spatial association is not a mere figment of his imagination, but a constrained experiential phenomenon consistent across sessions and automatically triggered by the visual presentation of numbers. We also show that this idiosyncratic representation can coexist with another implicit association, the SNARC effect (Spatial-Numerical Association of Response Codes, where small numbers are associated with the left side of space). This effect is present in individuals without explicit number forms and is not affected in the present subject in spite of his reversed subjective representation.


Factors influencing return to work of cancer survivors: a population-based study in Italy.
Little is known about return to work (RTW) of cancer survivors (CSs) in Central and Southern Europe. This study investigates the RTW rate of Italian CSs, describes their sick leave (SL) pattern, and explores factors affecting their RTW process. A population-based cross-sectional survey involving CSs registered at the Cancer Registry of Reggio Emilia Province (Italy) was launched in July 2016. Eligibility was restricted to individuals with first diagnosis of cancer in 2012 (stages I-III), aged 20-59, and employed at the time of diagnosis. Of the 266 individuals interviewed, 140 (52.6%) were reintegrated without difficulty, 113 (42.5%) returned to work with some difficulty, and 13 did not RTW (4.9%). The majority of CSs (56%) took SL for some periods during treatment. Age > 50 years and higher income seemed to facilitate RTW (RR = 0.65, 95% CI 0.49-0.88 and RR = 0.72, 95% CI 0.54-0.97, respectively), while being divorced acted as a barrier compared to being married (RR = 1.45, 95% CI 1.04-2.01). Individuals uncertain about the type of company they were working for reported greater difficulty in RTW (RR = 1.68, 95% CI 1.03-2.72). Individuals who had undergone chemotherapy and those perceiving physical limitations had a higher risk of difficulty in the RTW process (RR = 1.79, 95% CI 1.42-2.24 and RR = 1.59, 95% CI 1.25-2.02, respectively). Most CSs did RTW, with 2/3 combining work and treatment. However, almost half reported difficulty in RTW process. Factors affecting this process should be addressed throughout context-specific social and healthcare pathways aimed at preventing difficulties and potential job loss in this population.


Therapeutic arterial embolisation in children.
Arterial embolisation was performed in five paediatric patients. Indications were hypersplenism in two, gastrointestinal bleeding in two and treatment of an aneurysmal bone cyst in one. Embolisation provided definitive treatment in each case with no complications.


Postmenopausal bilateral oophorectomy is not associated with increased fracture risk in older women.
We studied whether oophorectomy performed after menopause is associated with an increased risk of hip or vertebral fractures in 6295 Study of Osteoporotic Fractures participants. There was no association between postmenopausal oophorectomy and the risk of hip or vertebral fractures. Bilateral oophorectomy after natural menopause has been associated with an increased risk of osteoporotic fractures, potentially because of a decline in serum estradiol and testosterone levels after the oophorectomy. We prospectively tested this hypothesis in the Study of Osteoporotic Fractures (SOF). We studied 6295 white women 65 years of age participating in the SOF who were not taking estrogen therapy at baseline. Hip fracture analyses included 708 hip fractures; vertebral fracture analyses included 267 incident vertebral fractures. Baseline serum estradiol and free testosterone values were available in a small subset of participants. There were no significant differences in age, weight, or BMD between the women who underwent postmenopausal oophorectomy (n = 583) and those who did not (n = 5712). Free testosterone levels were significantly lower among women who had a postmenopausal oophorectomy. A history of postmenopausal oophorectomy was not associated with an increased risk of hip (hazard ratio [HR] = 1.1; 95% CI = 0.9-1.5) or vertebral fracture (HR = 0.7; 95% CI = 0.5-1.2). The relationship between oophorectomy and hip fracture was not altered by adding serum estradiol level (HR = 1.3; 95% CI = 0.5-3.2) or serum free testosterone level (HR = 1.7; 95% CI = 0.8-3.7) to the model. In summary, postmenopausal oophorectomy was not associated with an increased risk of hip or vertebral fracture in this cohort. These results are in contrast to previous findings, suggesting that the relationship between postmenopausal oophorectomy and fractures is not fully elucidated and that incidental oophorectomy after menopause should still be considered carefully in each potential patient.


Macrohabitat associations of fishes in shallow waters of the Detroit River.
Seasonal variation in large-scale habitat selection by fishes in shallow, Canadian waters of the Detroit River was examined. Fish communities were compared among three river segments (upstream, middle and downstream) consisting of areas of shallow water habitat separated by wide hydrologic barriers of deep, flowing water and between inshore and offshore areas. In spring, the most unique, diverse and abundant fish assemblages were found at inshore sites in the middle segment where the largest remaining wetland habitats are located. Fishes used inshore habitat to spawn and probably avoided offshore areas because macrophyte cover was not available in spring. In summer, juvenile gizzard shad Dorosoma cepedianum and white bass Morone chrysops were observed in high densities in the upstream segment, probably migrating downstream from Lake St Clair. There was little difference in the fish assemblage among macrohabitats in autumn. The upstream segment appeared to be the most degraded, because it contained no species that were not found in the other segments, had a paucity of uncommon species and had significantly more non-native species. This state was attributed to the infilling of coastal wetlands by urban land use and a resulting loss of habitat heterogeneity. The middle segment, with the only remaining wetland habitats, had the greatest occurrence of uncommon species and the only species at risk found in this study. Conservation and restoration efforts should be greatest for wetlands; however, shallow offshore areas provide important fish habitat in summer and autumn.


NICE guidelines to improve TB management and prevention.
In the UK although the majority of the population is at very low risk of TB due to vaccination, the number of cases reported is increasing. In response NICE has released fresh guidance on prevention and treatment. Nurses can play a crucial role in adherence due to the extent of their patient contact.


HIV testing and sexual behavior among intravenous drug users in Bangkok, Thailand.
The relationships between previous HIV counseling and testing and sexual behavior were examined among injecting drug users in Bangkok. Six hundred one i.v. drug users (IVDUs) were recruited from drug treatment programs in November of 1989. A standardized interview on AIDS risk behavior was administered and a blood sample was collected for HIV testing of the 601 people. Fifty-six percent reported that they had not been previously tested (NPT), 15% had previously tested positive (PT+), and 29% had previously tested negative (PT-). Previous testing was associated with higher levels of safer sex and contraception with primary partners: 56% of the PT+ people with regular partners reported using condoms at least some of the time with that partner, compared with 28% of the PT- and only 20% of the NPT people. Similarly, 89% of the PT+ and 72% of the PT- people, compared with 59% of the NPT people, reported practicing some form of contraception with regular partners. The results strongly support the utility of HIV counseling and testing as a method of reducing heterosexual and perinatal HIV transmission among IVDUs in Bangkok.


Effect of melatonin on methamphetamine- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity and methamphetamine-induced behavioral sensitization.
Methamphetamine (METH)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity is thought to be associated with the formation of free radicals. Since evidence suggests that melatonin may act as a free radical scavenger and antioxidant, the present study was undertaken to investigate the effect of melatonin on METH- and MPTP-induced neurotoxicity. In addition, the effect of melatonin on METH-induced locomotor sensitization was investigated. The administration of METH (5 mg kg(-1) x 3) or MPTP (20 mg kg(-1) x 3) to Swiss Webster mice resulted in 45-57% depletion in the content of striatal dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 57-59% depletion in dopamine transporter binding sites. The administration of melatonin (10 mg kg(-1)) before each of the three injections of the neurotoxic agents (on day 1), and thereafter for two additional days, afforded a full protection against METH-induced depletion of dopamine and its metabolites and dopamine transporter binding sites. In addition, melatonin significantly diminished METH-induced hyperthermia. However, the treatment with melatonin had no significant effect on MPTP-induced depletion of the dopaminergic markers tested. In the set of behavioral experiments, we found that the administration of 1 mg kg(-1) METH to Swiss Webster mice for 5 days resulted in marked locomotor sensitization to a subsequent challenge injection of METH, as well as context-dependent sensitization (conditioning). The pretreatment with melatonin (10 mg kg(-1)) prevented neither the sensitized response to METH nor the development of conditioned locomotion. Results of the present study indicate that melatonin has a differential effect on the dopaminergic neurotoxicity produced by METH and MPTP. Since it is postulated that METH-induced hyperthermia is related to its neurotoxic effect, while regulation of body temperature is unrelated to MPTP-induced neurotoxicity or METH-induced locomotor sensitization, the protective effect of melatonin observed in the present study may be due primarily to diminishing METH-induced hyperthermia.


Hierarchies from D-brane instantons in globally defined Calabi-Yau orientifolds.
We construct the first globally consistent semirealistic type I string vacua on an elliptically fibered manifold where the zero modes of the Euclidean D1-instanton sector allow for the generation of nonperturbative Majorana masses of an intermediate scale. In another class of global models, a D1-brane instanton can generate a Polonyi-type superpotential breaking supersymmetry at an exponentially suppressed scale.


Coping with flow: behavior, neurophysiology and modeling of the fish lateral line system.
With the mechanosensory lateral line fish perceive water motions relative to their body surface and local pressure gradients. The lateral line plays an important role in many fish behaviors including the detection and localization of dipole sources and the tracking of prey fish. The sensory units of the lateral line are the neuromasts which are distributed across the surface of the animal. Water motions are received and transduced into neuronal signals by the neuromasts. These signals are conveyed by afferent nerve fibers to the fish brain and processed by lateral line neurons in parts of the brainstem, cerebellum, midbrain, and forebrain. In the cerebellum, midbrain, and forebrain, lateral line information is integrated with sensory information from other modalities. The present review introduces the peripheral morphology of the lateral line, and describes our understanding of lateral line physiology and behavior. It focuses on recent studies that have investigated: how fish behave in unsteady flow; what kind of sensory information is provided by flow; and how fish use and process this information. Finally, it reports new theoretical and biomimetic approaches to understand lateral line function.


[Comparative analysis of spatial EEG organization on models of non-verbal divergent and convergent thinking].
Features of neurophysiological organization of two main thinking types playing different roles in creative processes, i.e., divergent and convergent were studied with participation of 30 right-handed male subjects at the age from 30 to 50 years. Two tests were presented: (1) creation of many visual images on the basis of two simple geometrical figures (the model of divergent thinking) and (2) classification of a figure element with one of the offered standard samples (convergent thinking). The number of created images or correctly classified elements for five minutes served a criterion of performance productivity. It was found that performance of the divergent test with high productivity (as compared to low productivity) was characterized by a greater increase in non-linear interactions between the cortical potentials, especially in the axis right frontal--left occipital areas. At the same time, under conditions of high productivity, the number of active narrow-frequency spectral-coherent EEG bands increased. The data confirm the notion of neurophysiological organization of creative processes, according to which creative processes require the intensification of retrieval operations (both conscious and unconscious), based on extensive interhemispheric interaction and involvement of a system of EEG coherent structures oscillating with different frequencies.