Transcatheter Implantation of Interatrial Shunt Devices to Lower Left Atrial Pressure in Heart Failure.
Patients with heart failure with preserved ejection fraction (HFpEF) constitutes a considerable sized population like that of subjects with heart failure with reduced ejection fraction. The symptoms include exercise induced dyspnoea and fatigue besides an increased mortality rate when compared to the general population. There is limited evidence of benefit from pharmacological therapy. A main pathophysiological mechanism is a left ventricular filling pressure that might be near to normal during resting conditions but increases during exercise leading to pulmonary congestion. Based on observations like the apparent lesser symptomatology in patients with combined mitral valve stenosis and atrial septal defect (Lutembacher syndrome) when compared to patients with isolated mitral valve stenosis, several Inter-Atrial Shunt Devices (IASD) have been developed with the intent to unload the pressure in the left atrium by creating a shunt into the right atrium. Smaller studies have found that the IASDs reduce the left ventricular filling pressure during exercise and increase the functional status of patients both subjectively and objectively with reported low rates of complications. These devices are undergoing further investigations and might prove to be a new paradigm in the treatment of patients with HFpEF.


Progress in tear microdesiccate analysis by combining various transmitted-light microscope techniques.
Tear desiccation on a glass surface followed by transmitted-light microscopy has served as diagnostic test for dry eye. Four distinctive morphological domains (zones I, II, III and transition band) have been recently recognized in tear microdesiccates. Physicochemical dissimilarities among those domains hamper comprehensive microscopic examination of tear microdesiccates. Optimal observation conditions of entire tear microdesiccates are now investigated. One-μl aliquots of tear collected from individual healthy eyes were dried at ambient conditions on microscope slides. Tear microdesiccates were examined by combining low-magnification objective lenses with transmitted-light microscopy (brightfield, phase contrasts Ph1,2,3 and darkfield). Fern-like structures (zones II and III) were visible with all illumination methods excepting brightfield. Zone I was the microdesiccate domain displaying the most noticeable illumination-dependent variations, namely transparent band delimited by an outer rim (Ph1, Ph2), homogeneous compactly built structure (brightfield) or invisible domain (darkfield, Ph3). Intermediate positions of the condenser (BF/Ph1, Ph1/Ph2) showed a structured roughly cylindrical zone I. The transition band also varied from invisibility (brightfield) to a well-defined domain comprising interwoven filamentous elements (phase contrasts, darkfield). Imaging of entire tear microdesiccates by transmitted-light microscopy depends upon illumination. A more comprehensive description of tear microdesiccates can be achieved by combining illumination methods.


Signal processing strategies that improve performance and understanding of the quantitative ultrasound SPECTRAL FIT algorithm.
Quantifying the size of the tissue microstructure using the backscattered power spectrum has had limited success due to frequency-dependent attenuation along the propagation path, thus masking the frequency dependence of the scatterer size. Previously, the SPECTRAL FIT algorithm was developed to solve for total attenuation and scatterer size simultaneously [Bigelow et al., J. Acoust. Soc. Am. 117, 1431-1439 (2005)]. Herein, the outcomes from signal processing strategies on the SPECTRAL FIT algorithm are investigated. The signal processing methods can be grouped into two categories, viz., methods that improve the performance of the algorithm and methods that provide insight. The methods that improve the performance include compensating for the windowing function used to gate the time-domain signal, averaging the spectra in the normal frequency domain rather than the log domain to improve the precision of the scatterer size and attenuation estimates, improving the selection of the usable frequency range for the SPECTRAL FIT algorithm, and improving the compensation for electronic noise. The methods that provide insight demonstrate that the anomalous rapid fluctuations of the backscattered power spectrum do not affect the SPECTRAL FIT algorithm, and accurate attenuation estimates can be obtained even when the correct scatterer geometry (i.e., form factor) is not known.


The Ras/Raf/ERK signalling pathway drives Schwann cell dedifferentiation.
Schwann cells are a regenerative cell type. Following nerve injury, a differentiated myelinating Schwann cell can dedifferentiate and regain the potential to proliferate. These cells then redifferentiate during the repair process. This behaviour is important for successful axonal repair, but the signalling pathways mediating the switch between the two differentiation states remain unclear. Sustained activation of the Ras/Raf/ERK cascade in primary cells results in a cell cycle arrest and has been implicated in the differentiation of certain cell types, in many cases acting to promote differentiation. We therefore investigated its effects on the differentiation state of Schwann cells. Surprisingly, we found that Ras/Raf/ERK signalling drives the dedifferentiation of Schwann cells even in the presence of normal axonal signalling. Furthermore, nerve wounding in vivo results in sustained ERK signalling in associated Schwann cells. Elevated Ras signalling is thought to be important in the development of Schwann cell-derived tumours in neurofibromatosis type 1 patients. Our results suggest that the effects of Ras signalling on the differentiation state of Schwann cells may be important in the pathogenesis of these tumours.


Evaluating compliance with the 2013 best practice guidelines for preventing surgical site infection in high-risk pediatric spine surgery.
Best Practice Guidelines (BPGs) were published one decade ago to decrease surgical site infection (SSI) in pediatric spinal deformity. Successful implementation has not been established. This study evaluated surgeon compliance with items on the BPG. We hypothesized that BPG authors and surgeons with more experience, higher caseload, and awareness of the BPG would have higher compliance. We queried North American and European surgeons, authors and non-authors, and members of various spine study groups on adherence to BPGs using an anonymous survey. Mean compliance scores (MCSs) were developed by correlating Likert responses with MCSs ("None of the time" = no compliance = MCS 0, "Sometimes" = weak to moderate = MCS 1, "Most of the time" = high = MCS 2, "All the time" = perfect = MCS 3). Of the 142 respondents, 73.7% reported high or perfect compliance. Average compliance scores for all guidelines was 2.2 ± 0.4. There were significantly different compliance scores between North American and European surgeons (2.3 vs 1.8, p < 0.001), authors and non-authors (2.5 vs. 2.2, p = 0.023), and surgeons with and without knowledge of the BPGs (2.3 vs. 1.8, p < 0.001). There was a weak correlation between BPG awareness and compliance (r = 0.34, p < 0.001) and no correlation between years in practice (r = 0.0, p = 0.37) or yearly caseload (r = 0.2, p = 0.78) with compliance. Compliance among our cohort of surgeons surveyed was high. North American surgeons, authors of the BPGs and those aware of the guidelines had increased compliance. Participation in a spine study group, years in practice, and yearly caseload were not associated with compliance. Level V-expert opinion.


The effect of electrostatic charge on the aspiration efficiencies of airborne dust samplers: with special reference to asbestos.
An experimental investigation has been conducted into the effects of electrostatic charge, carried by the dust particles and by the sampler itself, on the sampling of airborne dusts. Experiments covering both personal and static sampling and a range of sampler types were carried out in the laboratory for both fibrous asbestos and isometric silica gel dusts. Experiments also were carried out in the spinning shop of an asbestos textile factory. The results showed that the aspiration efficiency of the sampler always is reduced as the charge on the sampler increases, independently of the type of sampler and of whether it is used as a static or personal sampler. The effect is most marked when sampling takes place in calm air. It is concluded from the results that, for the levels of charge reached by samplers in most practical situations, the effects on aspiration efficiency will be small. Possible exceptions to this might occur, however, in workplace environments where relative humidity is very low, and charge levels of the sampler (or on the worker wearing the sampler) can become high.


Network therapy for cocaine abuse: use of family and peer supports.
Cocaine-dependent subjects were treated by psychiatric residents in a 24-week sequence of Network Therapy. This approach, developed for practitioners in solo practice, employs a cognitive-behavioral orientation in sessions with family and peers as well as in individual sessions. Of 47 subjects, 73% of all observed weekly urines were negative for cocaine, and 20 (45%) of the subjects had negative toxicologies in the last 3 scheduled samples. A positive outcome was associated with the number of network (but not individual) sessions attended and completion of the full treatment sequence. Results suggest the utility of Network Therapy, even in the hands of relatively naive therapists.


Quality assurance of medicines supplied to low-income and middle-income countries: poor products in shiny boxes?
In today's context of globalisation of pharmaceutical production and distribution, international and national procurement agencies play a de facto key role in defining the quality of medicines available in sub-Saharan Africa. We evaluated the compliance of a sample of pharmaceutical distributors active in sub-Saharan Africa with the standards of the WHO guideline 'Model Quality Assurance System (WHO MQAS) for procurement agencies', and we investigated factors favouring or hindering the adequate implementation of the guideline. We used mixed-methods methodology to analyse quantitative and qualitative data. The quantitative study consisted of a retrospective secondary analysis of data collected by QUAMED (Quality Medicines for all), a partnership that pleads for universal access to quality-assured medicines. The qualitative survey consisted of formal and informal interviews with key informants. We adopted an embedded multiple-case study design. Our analysis suggests that international distributors based in Europe perform, on average, better than sub-Saharan African distributors. However, some weaknesses are ubiquitous and concern critical processes, such as the initial selection of the products and the ongoing reassessment of their quality. This is due to several different factors: weak regulatory oversight, insufficient human/financial resources, weak negotiating power, limited judicial autonomy and/or lack of institutional commitment to quality. Our findings suggest that pharmaceutical distributors active in sub-Saharan Africa generally do not apply stringent criteria for selecting products and suppliers. Therefore, product quality is not consistently assured but depends on the requirements of purchasers. While long-term solutions are awaited, the WHO MQAS guideline should be used as an evaluation and training tool to upgrade current standards.


Microcephaly caused by congenital Zika virus infection and viral detection in maternal urine during pregnancy.
Currently Latin America is undergoing a major epidemic of Zika virus, which is transmitted by Aedes mosquitoes. Concern for Zika virus infection has been increasing as it is suspected of causing brain defects in newborns such as microcephaly and, more recently, potential neurological and autoimmune complications including Guillian-Barré syndrome and acute disseminated encephalomyelitis. We describe a case of virus infection in a 25-year-old woman during the first trimester of her pregnancy, confirmed by laboratory tests only for the detection of viral particles in maternal urine, with imaging studies demonstrating the progression of cranial and encephalic changes in the fetus and later in the newborn, such as head circumference reduction, cerebral calcifications and ventriculomegaly.


Modulation of catechol estrogen synthesis by rat liver microsomes: effects of treatment with growth hormone or testosterone.
The ability of GH from various mammalian species, administered to normal mature male rats by constant infusion, to decrease the hepatic 2-hydroxylation of estradiol (E2) to female levels, as measured by the release of 3H2O from [2-3H]E2, was determined. Rat and human GH (hGH) showed the highest activity while ovine GH was inactive. PRL (0.6 IU/h X kg) administered together with hGH (0.02 IU/h X kg) did not antagonize the feminizing action of GH. Infusion of hGH into male rats decreased the affinity of estradiol 2-hydroxylase for its steroid substrate and altered the linear Lineweaver-Burk plot towards a nonlinear hyperbolic plot characteristic of the female. The apparent Michaelis-Menten constant (Km) for the reaction was 1.69 microM for males and 2.75 microM for testosterone-treated ovariectomized females. An equal mixture of liver microsomes from male and female rats gave kinetic values similar to those observed with males alone. Neonatal imprinting with androgen did not alter the magnitude of the response of female rats to treatment with testosterone and/or GH at maturity and the androgen effect could only be shown in ovariectomized animals. The results with rats of different endocrine status were corroborated by the kinetic data and by the pattern of metabolites obtained with [4-14C]E2 when examined by TLC and autoradiography. The hormonal control of estradiol 2-hydroxylase, the key enzyme in catechol estrogen formation, and the contribution of sex-specific multiple forms of the enzyme to this reaction are discussed.


Oral health beliefs in diverse populations.
Using data from population-based samples of adults participating in the ICS-II USA study, and using principal components analysis, we constructed oral health belief measures corresponding to the Health Belief Model (HBM) dimensions. Tests of validity and reliability were performed. Scales measuring perceived benefit of preventive practices and seriousness of oral disease had the highest validity and reliability. We used multiple regression analysis to examine sociodemographic predictors of perceived benefits of preventive practices. Race-ethnicity and age cohort were significant predictors among Baltimore and San Antonio adults. White adults and middle-aged persons in both research locations were more likely to believe in the benefit of preventive practices. Female gender, higher educational attainment, and better self-rated health were significant indicators of more positive oral health beliefs in every research location. Results also characterize persons who place lower value on preventive practices (i.e., males, less-educated persons, and those reporting poorer self-rated health). The design of effective dental public health messages and outreach efforts requires an analysis of the individual's health orientation and the factors influencing oral health beliefs. Oral health education interventions designed to improve health beliefs should contain an evaluation component for assessing the impact of education on health practices and oral health status.


Guidelines for management of Bowen's disease: 2006 update.
This article represents a planned regular updating of the previous British Association of Dermatologists (BAD) guidelines for management of Bowen's disease. They have been prepared for dermatologists on behalf of the BAD. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines.


Quadrupole ion traps and trap arrays: geometry, material, scale, performance.
Quadrupole ion traps are reviewed, emphasizing recent developments, especially the investigation of new geometries, guided by multiple particle simulations such as the ITSIM program. These geometries include linear ion traps (LITs) and the simplified rectilinear ion trap (RIT). Various methods of fabrication are described, including the use of rapid prototyping apparatus (RPA), in which 3D objects are generated through point-by-point laser polymerization. Fabrication in silicon using multilayer semi-conductor fabrication techniques has been used to construct arrays of micro-traps. The performance of instruments containing individual traps as well as arrays of traps of various sizes and geometries is reviewed. Two types of array are differentiated. In the first type, trap arrays constitute fully multiplexed mass spectrometers in which multiple samples are examined using multiple sources, analyzers and detectors, to achieve high throughput analysis. In the second, an array of individual traps acts collectively as a composite trap to increase trapping capacity and performance for a single sample. Much progress has been made in building miniaturized mass spectrometers; a specific example is a 10 kg hand-held tandem mass spectrometer based on the RIT mass analyzer. The performance of this instrument in air and water analysis, using membrane sampling, is described.


[Effectiveness of mini incision and absorbable screw fixation for treatment of anterior cruciate ligament tibial eminence avulsion fracture].
To investigate the effectiveness of open reduction by mini incision and absorbable screw internal fixation for the treatment of anterior cruciate ligament (ACL) tibial eminence avulsion fracture. Between January 2006 and July 2012, 90 patients (90 knees) with ACL tibial eminence avulsion fracture were treated. There were 58 males and 32 females, aged from 10 to 58 years with an average of 33.7 years. The causes of injury were traffic accident injury in 60 cases, sports injury in 22 cases, and fallinginjury in 8 cases. The disease duration was 1-365 days with a median of 106 days. Combined injuries included 14 cases of meniscus injury, 5 cases of medial collateral ligament injury, and 3 cases of avulsion fracture of the anterior horn of the lateral meniscus. All patients underwent open reduction by mini incision and internal fixation with absorbable screw. Postoperative rehabilitation exercise was performed. Two patients had delayed healing of incision, and others obtained primary healing. All the patients were followed up 6-72 months (mean, 40.1 months). X-ray examination showed that bone union was achieved in all patients at 3-12 months after operation; nail tail came off in 7 cases at 4-13 months after operation, and the nail tail was taken out under arthroscopy. At 6-12 months after operation, the range of motion (ROM), Tegner score, Lysholm score, and International Knee Documentation Committee (IKDC) score were significantly increased when compared with preoperative ones (P < 0.05). A combination of open reduction by mini incision and absorbable screw internal fixation for the treatment of ACL tibial eminence avulsion fracture has the advantages of easy operation, firm fixation, and satisfactory functional rehabilitation, so it is a safe and effective method for the treatment of ACL tibial eminence avulsion fracture.


Evaluation of a 2-channel portable device and a predictive model to screen for obstructive sleep apnea in a laboratory environment.
Various portable monitors for identifying obstructive sleep apnea (OSA) have been investigated and reported to enable accurate recording of OSA severity. However, more information is needed from different populations. This study was conducted to evaluate the efficiency of a portable 2-channel sleep apnea device (SleepView) for screening OSA in the Chinese population. Ninety-three consecutive subjects underwent simultaneous SleepView testing and laboratory polysomnography (PSG) monitoring. Data were collected and blindly analyzed. The efficiency of the SleepView device and a newly established predictive model for identifying OSA was evaluated in comparison with PSG. Good agreement was evident between the SleepView and PSG based on the apnea-hypopnea index (AHI; r(2) = 0.84, P < .01). The median AHI yielded by the SleepView was higher than that of PSG: 33.2 (interquartile range of 10.5-53.3) versus 19.2 (interquartile range of 5.2-53.6). The sensitivity and specificity of the SleepView for a PSG AHI of ≥ 5 were 80.28% and 95.45%, respectively, and the cutoff was 16.8. The area under the receiver operating curve for PSG AHIs of ≥ 5, > 15, and > 30 was 0.923, 0.924, and 0.979, respectively. When the AHI and oxygen desaturation index calculated by the SleepView were combined with waist circumference, the new predictive model showed a higher sensitivity of 92.96% and a specificity of 95.45% for a PSG AHI of ≥ 5, and the corresponding area under the receiver operating curve was 0.983. The SleepView device exhibited acceptable diagnostic accuracy for OSA in the Chinese population, especially in the severe OSA group. A practical predictive model comprising waist circumference, AHI, and oxygen desaturation index obtained with the SleepView was highly effective for screening even mild OSA. This simple and practical device may serve as a useful tool to screen for OSA. Further studies are required to validate the diagnostic efficiency of the SleepView in the home environment and in different populations.


Association between Toxoplasma gondii exposure and paediatrics haematological malignancies: a case-control study.
The possible association between Toxoplasma gondii infection and paediatric haematological malignancies in a group of patients and control subjects was evaluated in the present study. We performed an age-, gender- and residence frequency-matched case-control study of 101 blood cancer patients under 18 years of age, all of which were treated in Amirkola Pediatric Hospital. One hundred and thirty-eight control samples were gathered from the outpatient clinic in the hospital. All cases and controls were tested for the presence of anti-Toxoplasma IgG antibodies and then IgG-positive subjects were evaluated for IgM antibodies by enzyme-linked immunoassays. Anti-T. gondii IgG antibodies were found in 37 (36.6%) of the cases and 12 (8.7%) subjects in the control group (odds ratio 6.07, 95% confidence interval 2.963-12.437, P < 0.0001). The median and interquartile range (IQR) of IgG titre from case group (7.7 (IQR 0.25-13.5)) was higher than the control (0.2 (IQR 0.1-0.5)) (P < 0.0001). The frequency of anti-T. gondii antibodies (IgG) in lymphoblastic leukaemia (acute lymphoblastic leukaemia), Hodgkin's lymphoma and T-cell lymphoma were 33 (31.9%), 3 (50%) and 1(100%), respectively. Anti-T. gondii IgM was not detected in the IgG-positive patients in case group. In the case subjects, no significant difference was seen in the positive rates of T. gondii infection between genders (37.3% in male; 35.7% in female; P = 0.52) and ages groups (P = 0.31). This study demonstrated that T. gondii infection is prevalent in children with blood cancer. It also showed that toxoplasmosis may possibly be linked with an increased risk of childhood haematologic malignancies. Furthermore, these results may be helpful in research on blood neoplasia aetiology.


Effect of Polydextrose Intake on Constipation in Japanese Dialysis Patients: A Triple-Blind, Randomized, Controlled Trial.
The objective of the present study was to evaluate bowel habits induced by ingestion of 10 g polydextrose (PDX) fed to Japanese hemodialysis (HD) patients. This was a randomized, placebo-controlled, triple-blind, parallel-group controlled, 8-wk study. A total of 50 HD outpatients capable of self-management (51-79 y of age) were recruited at H Clinic, Japan. Inclusion criteria for participation in the study were ingestion of one or more laxative tablets for more than 3 mo and having received HD for more than 6 mo. The participants were randomly assigned to 2 groups: A (0 g polydextrose/d; control), B (10 g polydextrose/d; PDX). The primary outcome measure was stool frequency. Secondary outcomes were stool consistency, abdominal pain, intestinal bloating and clinical biochemistry indexes. PDX had no significant effect on blood biochemistry indexes. The PDX group showed significant improvements in bowel function (stool frequency increased from 3.0 times per week to 7.5 times per week) and reported no laxation problems (abdominal distention, cramps, and diarrhea) (p<0.01). Regular consumption of the PDX products increased dietary fiber intake to recommended levels and improved bowel habits.


Non-union and avascular necrosis of delayed reduction and screw fixation in displaced femoral neck fracture in young adults.
Management of displaced femoral neck fracture is crucial and vulnerable to develop complications. The present study was performed to evaluate the clinical outcome of delayed reduction with multiple screw fixations in young patients who had displaced femoral neck fracture. The authors conducted a retrospective study in young patients, aged less than 50 years old, who underwent delayed fixation for traumatic displaced femoral neck fracture (Garden classification III or IV) at Phetchabun Hospital between 1997 and 2002. Either closed or open reduction was performed to achieve an acceptable alignment and fixed with 2 or 3 cancellous screws. Study factors were age, gender Garden classification, time to reduction, type of reduction, number of screw fixation and Garden alignment index. Non-union and avascular necrosis was assessed by clinical and radiographic findings. There were 26 eligible patients. The average duration of delayed surgery was 13 days (range 2 to 30 days). Twenty-three patients had completed followed-up at average 28.4 months (range 14-52 months). All patients revealed complete union and independently ambulated within 10-16 months postoperatively. Clinical and radiographic avascular necroses of the femoral head developed in 2 patients (8.7%) at 20 and 24 months after surgery. Three patients who had early fixation failure underwent hemiarthroplasty except one patient refused to re-operate. Within 30-day delayed reduction and screw fixation for the treatment of displaced femoral neck fracture in the young is still good alternative treatment to preserve the femoral head with low rate of avascular necrosis.


Effects of a parallel-arm randomized controlled weight loss pilot study on biological and psychosocial parameters of overweight and obese breast cancer survivors.
Weight gain often occurs after breast cancer (BC) diagnosis and obesity along with sedentary behavior are associated with increased risk of BC recurrence and mortality. The primary objective of this study was to determine whether a significant weight loss, of approximately 10%, would lead to beneficial changes in biomarkers associated with cancer and/or cancer recurrence, and quality of life (QOL) in overweight and obese BC survivors. This parallel-arm study took place in Minneapolis, Minnesota, from January 2009 until March 2010. Participants were overweight and obese postmenopausal BC survivors who had completed treatment at least 3 months prior to enrollment and who did not smoke. Twenty-one BC survivors were randomized, via a random number generator computer software, to a 1000-calorie deficit feeding and exercise intervention (CR) or a weight management counseling intervention (WM) for 12 weeks followed by a 6-week follow-up. Body weight, biomarkers, and QOL were measured at baseline, weeks 6, 12, and 18. Body composition and fitness level were measured at only two time points. Twenty-one women were enrolled into the study and 20 completed all time points. Weight loss occurred with both interventions. Body weight in CR changed from 85.5 (95% confidence interval (CI) 77, 94) kg to 76.7 (95% CI 68.1, 85.2) kg, whereas in WM it changed from 98.3 (95% CI 89.8, 106.8) kg to 93.2 (95% CI 84.6, 101.7) kg. Fitness in CR changed from 4.9 (95% CI 4, 5.8) to 6.3 (95% CI 5.4, 7.2). CR led to lower plasma levels of leptin, F2-isoprostanes, and CRP. Quality of life seemed to improve with both interventions, while sleep quality decreased only in CR. Overweight and obese BC survivors were able to adhere to a strict diet and exercise program, which significantly decreased body weight, increased fitness level, and improved biomarkers and QOL. However, the strict dietary intervention in CR seemed to decrease participants' sleep quality and social relationships. Future larger randomized controlled trials should focus on behavioral modification and personalized nutrition counseling to help breast cancer survivors achieve a sustainable weight loss and fitness level. ClinicalTrials.gov identifier: NCT02940470.


Runx3 specifies lineage commitment of innate lymphoid cells.
Subsets of innate lymphoid cells (ILCs) reside in the mucosa and regulate immune responses to external pathogens. While ILCs can be phenotypically classified into ILC1, ILC2 and ILC3 subsets, the transcriptional control of commitment to each ILC lineage is incompletely understood. Here we report that the transcription factor Runx3 was essential for the normal development of ILC1 and ILC3 cells but not of ILC2 cells. Runx3 controlled the survival of ILC1 cells but not of ILC3 cells. Runx3 was required for expression of the transcription factor RORγt and its downstream target, the transcription factor AHR, in ILC3 cells. The absence of Runx3 in ILCs exacerbated infection with Citrobacter rodentium. Therefore, our data establish Runx3 as a key transcription factor in the lineage-specific differentiation of ILC1 and ILC3 cells.


Kinetic characterization of individual hexose transporters of Saccharomyces cerevisiae and their relation to the triggering mechanisms of glucose repression.
In Saccharomyces cerevisiae, there are a large number of genes (HXT1-HXT17/SNF3/RGT2) encoding putative hexose transporters which, together with a galactose permease gene (GAL2), belong to a superfamily of monosaccharide facilitator genes. We have performed a systematic analysis of the HXT1-7 and GAL2 genes and their function in hexose transport. Glucose uptake was below the detection level in the hxt1-7 null strain growing on maltose. Determination of the kinetic parameters of individual hexose transporter-related proteins (Hxtp) expressed in the hxt null background revealed Hxt1p and Hxt3p as low-affinity transporters (Km(glucose) = 50-100 mM), Hxt2p and Hxt4p as moderately low in affinity (Km(glucose) about 10 mM), and Hxt6p, Hxt7p as well as Gal2p as high-affinity transporters (Km(glucosse) = 1-2 mM). However, Hxt2p kinetics in cells grown on low glucose concentrations showed a high-affinity (Km = 1.5 mM) and a low-affinity component (Km = 60 mM). Furthermore, we investigated the involvement of glucose transport in glucose signalling. Glucose repression of MAL2, SUC2 and GAL1 was not dependent on a specific transporter but, instead, the strength of the repression signal was dependent on the level of expression, the properties of the individual transporters and the kind of sugar transported. The strength of the glucose repression signal correlated with the glucose consumption rates in the different strains, indicating that glucose transport limits the provision of a triggering signal rather then being directly involved in the triggering mechanism.


Longitudinal change in dysarthria associated with Friedreich ataxia: a potential clinical endpoint.
CNS functions that show change across short periods of time are particularly useful clinical endpoints for Friedreich ataxia. This study determined whether there is measurable acoustical change in the dysarthria associated with Friedreich ataxia across yearly intervals. A total of 29 participants diagnosed with Friedreich ataxia were recorded across 4 years at yearly intervals. A repeated measures ANOVA was used to determine which acoustic measures differed across time, and pairwise t tests were used to assess the consistency of the change across the time intervals. The relationship between the identified measures with perceptual severity was assessed with stepwise regression. Significant longitudinal change was observed with four measures that relate to the utterance duration and spectral changes in utterances. The spectral measures consistently detected change across time intervals of two or more years. The four measures combined moderately predicted perceptual severity. Together, the results implicate longitudinal change in speaking rate and utterance duration. Changes in speech associated with Friedreich ataxia can be measured across intervals of 2 years and therefore show rich potential for monitoring disease progression and therapy outcomes.


Sinusitis: when to treat and how.
When a common viral infection is mistaken for bacterial sinusitis, the antibiotics prescribed for it can contribute to the spread of antibiotic-resistant strains of bacteria. Here's what you need to know to correctly determine which type of sinusitis is making your patient miserable and treat it effectively.


Laparoscopic Adjustable Gastric Banding: Predictive Factors for Weight Loss and Band Removal After More than 10 Years' Follow-Up in a Single University Unit.
Weight loss and overall outcomes following laparoscopic adjustable gastric banding (LAGB) are more variable than with other bariatric procedures. Our aim was to investigate the predictive value of certain parameters in a cohort of 794 patients with 10 years' minimum follow-up after LAGB. We retrospectively reviewed the records of 794 patients undergoing LAGB performed by the authors between April 1996 and December 2004. We collected patients' data on weight loss and band-related complications and performed logistic regression modelling and calculated Kaplan-Meier curves for band preservation. The follow-up rate at 10 years was 90.4%. The mean follow-up duration was 15.1 years (range, 120-228 months). Overall band removal with or without conversion or replacement was required in 304 (38.2%) patients. The mean survival time of the band was 148.4 months (95% confidence interval: 138.3-167.4), and there was no difference in the rate of removal by operative technique (p = 0.7). The highest rate of band removal occurred in female patients (p = 0.05), those with BMI > 50 kg/m2 (p = 0.005) and in those <40 years of age (p = 0.04). For patients with the band in situ, the success rate was significantly lower in patients with initial BMI > 50 kg/m2. Conversely, differences in success rate were not statistically significant for age (using 50 years as the cut-off), technique or sex. Higher rates of removal occurred in women, younger patients and those with BMI > 50 kg/m2. Regardless of these criteria, the rate of band removal for complications rose over time. Patients should be informed of the high risk of the need for band removal long-term.


A prospective cohort study investigating factors associated with depression during medical internship.
Although the prevalence of depression among medical interns substantially exceeds that of the general population, the specific factors responsible are not well understood. Recent reports of a moderating effect of a genetic polymorphism (5-HTTLPR) in the serotonin transporter protein gene on the likelihood that life stress will precipitate depression may help to understand the development of mood symptoms in medical interns. To identify psychological, demographic, and residency program factors that are associated with depression among interns and to use medical internship as a model to study the moderating effects of this polymorphism. A prospective cohort study. Thirteen US hospitals. Seven hundred forty interns entering participating residency programs. Subjects were assessed for depressive symptoms using the 9-item Patient Health Questionnaire (PHQ-9), a series of psychological traits, and the 5-HTTLPR genotype prior to internship and then assessed for depressive symptoms and potential stressors at 3-month intervals during internship. The PHQ-9 depression score increased from 2.4 prior to internship to a mean of 6.4 during internship (P < .001). The proportion of participants who met PHQ-9 criteria for depression increased from 3.9% prior to internship to a mean of 25.7% during internship (P < .001). A series of factors measured prior to internship (female sex, US medical education, difficult early family environment, history of major depression, lower baseline depressive symptom score, and higher neuroticism) and during internship (increased work hours, perceived medical errors, and stressful life events) was associated with a greater increase in depressive symptoms during internship. In addition, subjects with at least 1 copy of a less-transcribed 5-HTTLPR allele reported a greater increase in depressive symptoms under the stress of internship (P = .002). There is a marked increase in depressive symptoms during medical internship. Specific individual, internship, and genetic factors are associated with the increase in depressive symptoms.


Remission associated with human herpesvirus infection in west syndrome.
Generally, West syndrome is an intractable epileptic syndrome in infancy, although spontaneous remission has been reported in some cases. An immunologic response to infection might be one of the factors involved in the remission of West syndrome, but the mechanisms remain unknown. On the other hand, exanthema subitum is a common disease occurring in infancy with the characteristics of fever and rash. Two kinds of human herpesvirus, 6 and 7, have been isolated as causal agents of exanthema subitum. We experienced one symptomatic case and three cryptogenic cases of West syndrome that showed spontaneous remission. In the symptomatic case, the subject showed a temporary remission; however, in the other cases, the remissions were long term. In the present study, we report the patients' improvement and electroencephalographic (EEG) findings. In all of our cases, hypsarrythmia disappeared on the EEG findings, the human herpesvirus 6 IgG antibodies increased in all four cases, and the herpesvirus 7 IgG antibodies increased in two cases. We postulate that the remission of the four cases proceeded from infection by exanthema subitum. The changes in serum antibody values suggest that the spontaneous remission of West syndrome was related to human herpesvirus 6 and 7 infections.


Pyoderma gangrenosum associated with Takayasu's arteritis.
Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterized by destructive, necrotizing and noninfective ulceration of the skin mostly on lower extremities. PG is well known as a complication of Takayasu's arteritis in Japan. However, this association is not commonly observed in North American and European patients. We describe a case of PG that was associated with Takayasu's arteritis who was successfully treated with systemic cyclosporin. We have reviewed 35 well-documented PG cases with Takayasu's arteritis in comparison to 106 PG cases without Takayasu's arteritis. The results demonstrate that this association occurs predominantly in young females and that these cases exhibit more widespread PG lesions.


[Concept and outcome of general practice quality circles on the topic of diabetes mellitus].
In Saxonia, an agreement of shared care was reached between health insurances and the society of general practitioners with the objective to have a better medical care for patients with diabetes mellitus. This model of shared care means integrated medical care for out-patient diabetics between general practitioner and specialists. It must be accompanied by quality assurance measures. After a training of moderators according to a structured programme of the Central Research Institute for Outpatient Health Care, quality circles started with seven to ten members and two moderators in five Saxonian cities in May 1994. General practitioners interactively improved their medical knowledge about diabetes mellitus during five sessions with two hours each. The regional specialist participated in the first and the last session. He also answered open questions left in a mail box. Based on patient data the following results were achieved: 553 documentations.


Microbiota from Alzheimer's patients induce deficits in cognition and hippocampal neurogenesis.
Alzheimer's disease is a complex neurodegenerative disorder leading to a decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor in Alzheimer's disease by showing specific alterations in the gut microbiome composition of Alzheimer's patients and in rodent models. However, it is unknown whether gut microbiota alterations are causal in the manifestation of Alzheimer's symptoms. To understand the involvement of Alzheimer's patient gut microbiota in host physiology and behaviour, we transplanted faecal microbiota from Alzheimer's patients and age-matched healthy controls into microbiota-depleted young adult rats. We found impairments in behaviours reliant on adult hippocampal neurogenesis, an essential process for certain memory functions and mood, resulting from Alzheimer's patient transplants. Notably, the severity of impairments correlated with clinical cognitive scores in donor patients. Discrete changes in the rat caecal and hippocampal metabolome were also evident. As hippocampal neurogenesis cannot be measured in living humans but is modulated by the circulatory systemic environment, we assessed the impact of the Alzheimer's systemic environment on proxy neurogenesis readouts. Serum from Alzheimer's patients decreased neurogenesis in human cells in vitro and were associated with cognitive scores and key microbial genera. Our findings reveal for the first time, that Alzheimer's symptoms can be transferred to a healthy young organism via the gut microbiota, confirming a causal role of gut microbiota in Alzheimer's disease, and highlight hippocampal neurogenesis as a converging central cellular process regulating systemic circulatory and gut-mediated factors in Alzheimer's.


Synchronous Primary Renal Lymphoma and Renal Cell Carcinoma: Collision Tumors in the Same Kidney.
Background: Primary renal lymphoma (PRL) is an exceptionally rare disease with under 50 reported cases in the literature. PRL is an aggressive condition that can present with nonspecific symptoms and local invasion mimicking renal cell carcinoma (RCC). We present an unusual case involving a collision tumor between PRL and RCC. Case Presentation: The patient is a 62-year-old immunosuppressed man with an incidental left renal mass on cross-sectional imaging. Renal mass biopsy confirmed clear cell type RCC. He underwent robot-assisted, laparoscopic left radical nephrectomy for presumed RCC without evidence for extrarenal disease or discernable lymphadenopathy. Final pathology revealed a collision tumor, including PRL and RCC. Conclusion: To our knowledge, this is the first reported case within the literature describing a collision tumor between PRL and RCC. Although rare, it is important to consider PRL in the differential diagnosis of a solid renal mass, especially in patients with a prior history of transplantation and/or chronic immunosuppression.


Safety and efficacy of photoselective vaporization of prostate in patients receiving anticoagulants.
Objective of the present study was to evaluate the safety and efficacy of photoselective vaporization of the prostate (PVP) using a 80W potassium titanyl phosphate (KTP) laser, in benign prostatic enlargement (BPE) patients who were on ongoing anticoagulant therapy during the perioperative period. Prospectively collected laser prostatectomy patient database of our hospital for the period between July 2009-Jan 2012 was retrospectively reviewed. Data on perioperative safety, functional outcome and complications up to follow-up at 6 months of 45 eligible patients who underwent PVP-KTP and were on perioperative anticoagulant therapy (study group) was compared with 47 eligible patients who underwent PVP-KTP and were not on perioperative anticoagulant therapy (control group). P<0.05 was considered statistically significant. The baseline characteristics of the two groups were similar except for ASA score which was significantly higher in the study group.(2.64±0.60 vs. 1.53±0.50). Though the need (15.55% vs. 4.25% patients) and duration of postoperative irrigation (243.33±49.66 vs. 52.5±10.60 min) was significantly higher in the study group, the postoperative hemoglobin drop 24 hours postoperatively did not differ significantly between the two groups (8.54% vs. 6.48%). No patient required a blood transfusion. The overall complication rate was similar in the two groups. In both groups, significant improvement was recorded in the IPSS, QOL, Q max, PVRU and prostate volume data upto 6 months follow up with no significant differences noted. KTP-PVP can be performed safely and effectively in BPE patients on ongoing anticoagulation, without increasing the risk of perioperative bleeding or the need for blood transfusion.


The effect of detergents on bovine adrenal ferredoxin.
The incubation of adrenal ferredoxin with various detergents in the presence of oxygen or ferricyanide leads to bleaching of the protein. The bleached preparation has the properties of apoferredoxin and it can be reconstituted with high yield by conventional methods.


Audiovisual synchrony detection for fluent speech in early childhood: An eye-tracking study.
During childhood, the ability to detect audiovisual synchrony gradually sharpens for simple stimuli such as flashbeeps and single syllables. However, little is known about how children perceive synchrony for natural and continuous speech. This study investigated young children's gaze patterns while they were watching movies of two identical speakers telling stories side by side. Only one speaker's lip movements matched the voices and the other one either led or lagged behind the soundtrack by 600 ms. Children aged 3-6 years (n = 94, 52.13% males) showed an overall preference for the synchronous speaker, with no age-related changes in synchrony-detection sensitivity as indicated by similar gaze patterns across ages. However, viewing time to the synchronous speech was significantly longer in the auditory-leading (AL) condition compared with that in the visual-leading (VL) condition, suggesting asymmetric sensitivities for AL versus VL asynchrony have already been established in early childhood. When further examining gaze patterns on dynamic faces, we found that more attention focused on the mouth region was an adaptive strategy to read visual speech signals and thus associated with increased viewing time of the synchronous videos. Attention to detail, one dimension of autistic traits featured by local processing, has been found to be correlated with worse performances in speech synchrony processing. These findings extended previous research by showing the development of speech synchrony perception in young children, and may have implications for clinical populations (e.g., autism) with impaired multisensory integration.


Tyrosylprotein sulfotransferase-2 expression is required for sulfation of RNase 9 and Mfge8 in vivo.
Protein-tyrosine sulfation is mediated by two Golgi tyrosyl-protein sulfotransferases (TPST-1 and TPST-2) that are widely expressed in vivo. However, the full substrate repertoire of this enzyme system is unknown and thus, our understanding of the biological role(s) of tyrosine sulfation is limited. We reported that whereas Tpst1(-/-) male mice have normal fertility, Tpst2(-/-) males are infertile despite normal spermatogenesis. However, Tpst2(-/-) sperm are severely defective in their motility in viscous media and in their ability to fertilize eggs. These findings suggest that sulfation of unidentified substrate(s) is crucial for normal sperm function. We therefore sought to identify tyrosine-sulfated proteins in the male genital tract using affinity chromatography on PSG2, an anti-sulfotyrosine monoclonal antibody, followed by mass spectrometry. Among the several candidate tyrosine-sulfated proteins identified, RNase 9 and Mfge8 were examined in detail. RNase 9, a catalytically inactive RNase A family member of unknown function, is expressed only in the epididymis after onset of sexual maturity. Mfge8 is expressed on mouse sperm and Mfge8(-/-) male mice are subfertile. Metabolic labeling coupled with sulfoamino acid analysis confirmed that both proteins are tyrosine-sulfated and both proteins are expressed at comparable levels in wild type, Tpst1(-/-), and Tpst2(-/-) epididymides. However, we demonstrate that RNase 9 and Mfge8 are tyrosine-sulfated in wild type and Tpst1(-/-), but not in Tpst2(-/-) mice. These findings suggest that lack of sulfation of one or both of these proteins may contribute mechanistically to the infertility of Tpst2(-/-) males.


Engineered proteins pull double duty.
Myriad bi-specific proteins have been developed that recognize two different clinical targets, with the goal of achieving enhanced therapeutic effects as compared with proteins that interact with only one target. These engineered proteins are starting to enter clinical testing for a variety of biomedical applications, particularly cancer treatment.


Hole array enhanced dual-band infrared photodetection.
Photonic structures have been attracting more attention due to their ability to capture, concentrate and propagate optical energy. In this work, we propose a photon-trapping hole-array structure integrated in a nip InAsSb-GaSb heterostructure for the enhancement of the photoresponse in both near- and mid-infrared regions. The proposed symmetrical hole array can increase the photon lifetime inside the absorption layer and reduce reflection without polarization dependence. Significant enhancements in absorption and photoelectric conversion efficiency are demonstrated in dual bands for unpolarized incidence. The enhancement factors of responsivity at room temperature under zero-bias are 1.12 and 1.33 for the near- and mid-infrared, respectively, and they are increased to 1.71 and 1.79 when temperature drops to the thermoelectric cooling temperature of 220 K. Besides, such an integrated hole array also slightly improves working frequency bandwidth and response speed. This work provides a promising way for high-efficiency polarization-independent photoelectric conversion in different electromagnetic wave ranges.


Antithyroid treatment of maternal hyperthyroidism during lactation.
Eleven pregnant women were treated for hyperthyroidism with carbimazole (CZ) and one with propylthiouracil (PTU). Based upon a previous study it was decided that lactation should be permitted if the dose required after delivery did not exceed 15 mg of CZ or 150 mg of PTU. In the patients studied here the daily dose of CZ varied from 5 to 15 mg and that of PTU was 125 mg. TSH was measured in cord blood and in the blood of the newborn infants usually after 2 and 3 weeks of lactation. Serum T4 was measured serially in the infants' blood from day 4 up to 21 day of age, at least. In all instances the TSH concentration in cord blood remained below 45 mU/l the level used in screening for neonatal hypothyroidism. Serum TSH and T4 were all within the appropriate reference limits during the 3 weeks of study with only one exception. In the infant whose mother was treated with PTU the serum T4 measured 5 d after birth was slightly below the lower limit but later returned to normal. Since serum TSH and T4 did not deviate from the reference range in newborn infants during lactation, we conclude that breast-feeding can be permitted if the daily dose of CZ does not exceed 15 mg (or 150 mg of PTU) and if facilities are available for measuring neonatal serum TSH and T4.


The clarification and assessment of a method of psychotherapy.
The 'conversational model' of psychotherapy was investigated with a view to discovering which behaviours distinguish psychotherapists trained in this method from others, of equal clinical experience. A rating scheme designed to capture the theoretical aspects of the model, and 30 predictions were made concerning behaviours which were expected to distinguish the psychotherapists. Five psychotherapists were matched to five psychiatrists who had not been trained in this method; each doctor took on four patients for therapy, and each patient was seen on five occasions. All interviews were recorded, and excerpts from the recordings rated. Only ten of the 30 predictions were upheld. In ten further predictions, the psychotherapists displayed the appropriate behaviours, but the behaviours were not peculiar to the model, since eclectic psychiatrists also displayed them. Six model behaviours were not practised frequently by the psychotherapists, and four 'non-model' behaviours were equally common in either group. The research formed the basis for the preparation of materials to teach psychotherapeutic skills in a more efficient way.


The future of aptamers in medicine.
Aptamers, simply described as chemical antibodies, are synthetic oligonucleotide ligands or peptides that can be isolated in vitro against diverse targets including toxins, bacterial and viral proteins, virus-infected cells, cancer cells and whole pathogenic microorganisms. Aptamers assume a defined three-dimensional structure and generally bind functional sites on their respective targets. They possess the molecular recognition properties of monoclonal antibodies in terms of their high affinity and specificity. The applications of aptamers range from diagnostics and biosensing, target validation, targeted drug delivery, therapeutics, templates for rational drug design to biochemical screening of small molecule leads compounds. This review describes recent progress made in the application of biomedically relevant aptamers and relates them to their future clinical prospects.


Stable isotopes and bioelectrical impedance for measuring body composition in infants born small for gestational age.
The assessment of body composition in infants born small for gestational age (SGA) is required primarily to evaluate nutritional status and to monitor growth in the neonatal period. Measurement of total body water, using stable isotopes of hydrogen (2H) and oxygen (18O), offers a potential method by which body composition can be assessed. This technique is non-invasive and recently has been used successfully in a cohort of 5-week-old infants born SGA. Nevertheless, the assessment of total body water using stable isotopes requires specialized laboratories and equipment, which may limit its use. Prediction of total body water by bioelectrical impedance is a possible alternative. This technique uses electrical theory to predict the volume of the conducting medium in the body, namely, water. A potential limitation of bioelectrical impedance analysis is the accuracy, which may impinge on its usefulness in small infants.


[Preoperative Preparation: Patient Blood Management - What is Optimal?]
Patient Blood Management (PBM) focusses on anemia management, the minimization of (unnecessary) iatrogenic blood loss and the exhaustion of natural tolerance to anemia with rational use of red blood cell transfusion. The focus of the current review article is now the preoperative phase with the following PBM components: management of anemia, pre-transfusion analytics and management of anticoagulants. Preoperative anemia is an independent risk factor for increased perioperative morbidity and mortality. In elective surgery, the causes of anemia should be diagnosed prior to surgery as early as possible, and if indicated, a specific treatment for treatable causes should be initiated. Preoperative pre-transfusion analytics should be performed by a step-wise approach depending on the transfusion probability (and the baseline hemoglobin) and current in-house data. Management of (oral) anticoagulants needs to consider an individual risk stratification for bleeding and thromboembolic events, should be initiated in the preoperative phase, and should specify whether the anticoagulant needs to be continued, stopped or bridged. Long-term success of the preoperative PBM program can only be guaranteed with clearly defined responsibilities in the preoperative PBM team, communication and training of all those involved in the process of care.


The Cryo-EM structure of a complete 30S translation initiation complex from Escherichia coli.
Formation of the 30S initiation complex (30S IC) is an important checkpoint in regulation of gene expression. The selection of mRNA, correct start codon, and the initiator fMet-tRNA(fMet) requires the presence of three initiation factors (IF1, IF2, IF3) of which IF3 and IF1 control the fidelity of the process, while IF2 recruits fMet-tRNA(fMet). Here we present a cryo-EM reconstruction of the complete 30S IC, containing mRNA, fMet-tRNA(fMet), IF1, IF2, and IF3. In the 30S IC, IF2 contacts IF1, the 30S subunit shoulder, and the CCA end of fMet-tRNA(fMet), which occupies a novel P/I position (P/I1). The N-terminal domain of IF3 contacts the tRNA, whereas the C-terminal domain is bound to the platform of the 30S subunit. Binding of initiation factors and fMet-tRNA(fMet) induces a rotation of the head relative to the body of the 30S subunit, which is likely to prevail through 50S subunit joining until GTP hydrolysis and dissociation of IF2 take place. The structure provides insights into the mechanism of mRNA selection during translation initiation.


Detection of respiratory syncytial virus RNA in blood of neonates by polymerase chain reaction.
During the winter season of 1994/1995, nasopharyngeal aspirates and blood samples of neonates who were admitted to the Neonatal Intensive Care Unit (NICU) (group 1) and infants with respiratory tract disease (group 2) were examined prospectively for the presence of respiratory syncytial virus (RSV). Examination of nasal washes were done by antigen detection and blood samples were tested by nested reverse transcription and polymerase chain reaction (RT-PCR). The results of the 41 neonates studied were as follows: 14/41 were positive for RSV antigen in nasal washes and for RSV-RNA in blood, 5/41 were only RSV antigen positive, 13/41 neonates had negative nasal washes; 6 had positive RT-PCR results in blood. In 9/41 cases only blood samples were available. Five of these were positive by RT-PCR testing. Group 2 included 20 infants hospitalized with respiratory tract disease, e.g., pneumonia, bronchiolitis, or Upper Respiratory Tract Infection (URTI). Eleven out of twenty were positive for RSV antigen in nasal washes and 6/20 were also positive for RSV-RNA in blood. The conclusion is that viremia may be a frequent occurrence in neonates and young children.


Pharmacotherapy of methamphetamine addiction: an update.
Methamphetamine dependence is a serious public health problem worldwide for which there are no approved pharmacological treatments. Psychotherapy is still the mainstay of treatment; however, relapse rates are high. The search for effective pharmacological treatment has intensified in the last decade. This review will highlight progress in pharmacological interventions to treat methamphetamine dependence as well as explore new pharmacological targets. Published data from clinical trials for stimulant addiction were searched using PubMed and summarized, as well as highlights from a recent symposium on methamphetamine pharmacotherapy presented at the ISAM 2006 meeting, including interim analysis data from an ongoing D-amphetamine study in Australia. Early pilot data are encouraging for administering D-amphetamine and methylphenidate as treatment for heavy amphetamine users. Abilify at 15 mg/day dose increased amphetamine use in an outpatient pilot study. Sertraline, ondansetron, baclofen, tyrosine, and imipramine were ineffective in proof-of-concept studies. Development of pharmacotherapy for methamphetamine dependence is still in an early stage. Data suggesting D-amphetamine and methylphenidate as effective pharmacotherapy for methamphetamine addiction will need to be confirmed by larger trials. Preclinical data suggest that use of GVG, CB1 antagonist, and lobeline are also promising therapeutic strategies.


Application of capability indices and control charts in the analytical method control strategy.
In this study, we assessed the usefulness of control charts in combination with the process capability indices, Cpm and Cpk , in the control strategy of an analytical method. The traditional X-chart and moving range chart were used to monitor the analytical method over a 2-year period. The results confirmed that the analytical method is in-control and stable. Different criteria were used to establish the specifications limits (i.e. analyst requirements) for fixed method performance (i.e. method requirements). If the specification limits and control limits are equal in breadth, the method can be considered "capable" (Cpm = 1), but it does not satisfy the minimum method capability requirements proposed by Pearn and Shu (2003). Similar results were obtained using the Cpk index. The method capability was also assessed as a function of method performance for fixed analyst requirements. The results indicate that the method does not meet the requirements of the analytical target approach. A real-example data of a SEC with light-scattering detection method was used as a model whereas previously published data were used to illustrate the applicability of the proposed approach.


Use of avidin-biotin-glucose oxidase complex to detect antimalarial antibody in serum by light microscopy.
An immunohistochemical assay was developed combining an avidin-biotin-glucose oxidase complex procedure (ABC-GO) with light microscopy to detect specific antibody against Plasmodium falciparum. Thin blood films were prepared from culture material of P. falciparum and fixed with acetone. Antibody was detected by successive incubations with test serum, biotinylated goat antihuman antibody, avidin-biotin-glucose oxidase complex, and glucose oxidase substrate. In the presence of reactive serum, a blue precipitate formed on the parasites and could be visually observed with a 40x objective. Sera from patients with single infections for P. vivax or P. ovale were unreactive. No cross-reactivity was observed with sera from patients with rheumatoid arthritis, filariasis, amebiasis, schistosomiasis, dengue, scrub typhus, leptospirosis, or toxoplasmosis. The sensitivity of ABC-GO is comparable to that of the indirect fluorescent antibody test.


Bone cement cardiac and pulmonary embolism.
This case describes a complication of bone cement use. A 65-year-old male patient with back spine trauma caused by a fall, underwent a percutaneous vertebroplasty. Five years later, he consulted for palpitations, and the electrocardiogram showed supraventricular arrhythmia. A transthoracic two-dimensional echocardiography showed a hyperechogenic linear structure of 7 cm length, running from the lateral wall of the right ventricle to the right atrium through the tricuspid valve. This foreign body, which was suspicious for bone cement embolism, appeared rigid and was attached at the lateral wall of the right ventricle, with its proximal end free in the right atrium. The tip of the cement embolus was inside the myocardium of the lateral wall of the right ventricle, with risk of cardiac perforation. A fluoroscopy was performed, which confirmed the presence of cement within the right heart, with great mobility in each cardiac cycle. Chest computed tomography (CT) and multidetector CT three-dimensional reconstruction confirmed the presence of cement within the right heart. Chest CT showed two pulmonary embolisms, one in the right upper lobe and one in the left lower pulmonary lobe. This case emphasizes the risk of late clinical manifestations of cardiac and pulmonary embolism of methylmethacrylate after percutaneous vertebroplasty, suggesting that the risk of such embolism might be underestimated. We propose routine chest radiography, two-dimensional echocardiography, and chest CT after every percutaneous vertebroplasty, to detect asymptomatic cardiac and pulmonary embolism and thereby prevent serious delayed cardiopulmonary failures.


The influence of hormonal changes during menstrual cycle on serum adiponectin concentrations in healthy women.
Adiponectin is an adipocyte-derived hormone involved in the regulation of carbohydrate and lipid metabolism. Its concentrations are decreased in patients with obesity, type 2 diabetes and atherosclerosis and are higher in females than in males. Gender differences of adiponectin levels raise the possibility that sex hormones directly regulate its serum concentrations, which may in turn influence insulin sensitivity in different phases of the menstrual cycle. To test this hypothesis we measured serum adiponectin, estradiol, progesterone, luteinizing hormone and follicle-stimulating hormone concentrations daily throughout the menstrual cycle in six healthy women. Mean adiponectin levels strongly positively correlated with serum cortisol concentrations [R=0.94286; p=0.0048 (Spearman correlation test)], but were not significantly related to other anthropometric, biochemical and hormonal characteristics of the subjects (BMI, blood glucose, insulin, testosterone, prolactin, cholesterol, HDL cholesterol, LDL cholesterol, triglycerides concentrations, or atherogenic index). Furthermore, no significant changes of serum adiponectin levels were found throughout the menstrual cycle. We conclude that changes in sex hormones during the menstrual cycle do not affect total circulating adiponectin levels in healthy women. Therefore, the differences in insulin sensitivity in various phases of the menstrual cycle are not due to changes of circulating adiponectin levels.


Sequence determinants of quaternary structure in lumazine synthase.
Riboflavin, an essential cofactor for all organisms, is biosynthesized in plants, fungi and microorganisms. The penultimate step in the pathway is catalyzed by the enzyme lumazine synthase. One of the most distinctive characteristics of this enzyme is that it is found in different species in two different quaternary structures, pentameric and icosahedral, built from practically the same structural monomeric unit. In fact, the icosahedral structure is best described as a capsid of twelve pentamers. Despite this noticeable difference, the active sites are virtually identical in all structurally studied members. Furthermore, the main regions involved in the catalysis are located at the interface between adjacent subunits in the pentamer. Thus, the two quaternary forms of the enzyme must meet similar structural requirements to achieve their function, but, at the same time, they should differ in the sequence traits responsible for the different quaternary structures observed. Here, we present a combined analysis that includes sequence-structure and evolutionary studies to find the sequence determinants of the different quaternary assemblies of this enzyme. A data set containing 86 sequences of the lumazine synthase family was recovered by sequence similarity searches. Seven of them had resolved three-dimensional structures. A subsequent phylogenetic reconstruction by maximum parsimony (MP) allowed division of the total set into two clusters in accord with their quaternary structure. The comparison between the patterns of three-dimensional contacts derived from the known three-dimensional structures and variation in sequence conservation revealed a significant shift in structural constraints of certain positions. Also, to explore the changes in functional constraints between the two groups, site-specific evolutionary rate shifts were analyzed. We found that the positions involved in icosahedral contacts suffer a larger increase in constraints than the rest. We found eight sequence sites that would be the most important icosahedral sequence determinants. We discuss our results and compare them with previous work. These findings should contribute to refinement of the current structural data, to the design of assays that explore the role of these positions, to the structural characterization of new sequences, and to initiation of a study of the underlying evolutionary mechanisms.


We're Going Digital: The Current State of CAD/CAM Dentistry in Prosthodontics.
This paper reviews the current state of computer-aided design and manufacturing (CAD/CAM) in dentistry, with a special focus on restorative dental applications. The potential, advantages, and limitations of the technology will be discussed, comparing the digital workflow to conventional techniques, based on contemporary clinical evidence. The technology does seem to offer a more streamlined and efficient means of treatment planning and delivery of care through reduced chairside time, with reported improved patient satisfaction. Nonetheless, the accuracy and treatment outcomes of CAD/CAM treatment modalities are inconsistent and do not support a superior performance to existing conventional techniques, rather a comparable one.


GP and patient perspectives on treatment with non-steroidal anti-inflammatory drugs for the treatment of pain in osteoarthritis.
Two nationwide surveys were carried out using an electronic poll of 2,000 GPs and postal questionnaires were sent to 30,000 patients with osteoarthritis (OA). Both surveys found a high level of gastro-intestinal (GI) side-effects in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). Almost every GP (97%) reported experience of patients suffering GI symptoms while on an NSAID, 38% reported patients who had been hospitalised and 4% reported patients who had died owing to NSAID-induced side-effects. Most GPs (92%) said they were concerned about GI safety when prescribing an NSAID and almost a third (32%) said they were concerned about litigation from patients who had experienced a bleed. Use of NSAIDs in OA remained high, with 44% of GPs prescribing conventional NSAIDs to at least three quarters of their patients, 57% of GPs using simple analgesia and just 12% using a cyclo-oxygenase-2 (COX-2) selective inhibitor in over 74% of patients. Some 45% of patients reported receiving NSAIDs compared with 43% on simple analgesia and 4% on COX-2 selective inhibitors. Most GPs (69%) stated that their main therapeutic objective in using an NSAID to treat OA was to control pain without GI side-effects. Almost a quarter (24%) said they used low-dose NSAIDs in the hope that this would control pain without GI side-effects. Dissatisfaction with treatment was the most common reason reported by GPs for patients on an NSAID to re-present, with 73% citing either breakthrough pain or incomplete pain relief as the most common reason for patient dissatisfaction. This mirrored the patients' perception, with 63% citing inadequate pain relief as their main reason for dissatisfaction with current painkillers compared to 17% who cited stomach upsets or irritation. Patient and GP appear to be united in their concern at the GI risks of NSAID treatment. In the light of this and recent data on the efficacy, safety profile and cost-effectiveness of COX-2 selective inhibitors, GPs should re-examine their medical management of OA.


Bioinspired Design and Fabrication of Polymer Composite Films Consisting of a Strong and Stiff Organic Matrix and Microsized Inorganic Platelets.
Intensive studies on nacre-inspired composites with exceptional mechanical properties based on an organic/inorganic hierarchical layered structure have been conducted; however, integrating high strength, stiffness, and toughness for engineering materials still remains a challenge. We herein report the design and fabrication of polymer composites through a hydrogel-film casting method that allow for building uniformly layered organic/inorganic microstructure. Alginate (Alg) was used for an organic matrix, whose mechanical properties were controlled by Ca2+ cross-linking toward the simultaneously strong, stiff, and tough resultant composite. Alumina (Alu) microplatelets were used for horizontally aligned inorganic phase, and their alignment and interactions with the organic matrix were improved by polyvinylpyrrolidone (PVP) coating on the platelet. The composite film exhibits well-balanced elastic and plastic deformation under tensile stress, leading to high stiffness and toughness, which have not been generally achieved in microplatelet-based composite films developed in previous studies. The synergistic effect of Ca2+ cross-linking and PVP-coated Alu platelets on the mechanical properties improved polymer-platelet interfacial interactions, and platelet alignment is clearly demonstrated through mechanical tests and Fourier transform infrared and X-ray diffraction analyses. We further demonstrate that the reinforcing effect of the Alu platelet and PVP-coated platelet on the mechanical properties is dependent on humidity. Such effects are maximized at highly dry conditions, which is consistent with the model estimation. Furthermore, a thick bulk composite was produced by laminating thin films and showed high mechanical properties under flexural stress. Our design and fabrication strategies combined with the understanding of their mechanism yield an alternative approach to produce engineered composite materials.


The Impact of Yoga on Fatigue in Cancer Survivorship: A Meta-Analysis.
Mind-body approaches, particularly yoga, are used by cancer survivors to cope with treatment-related symptoms. Consistency of yoga-related effects on treatment-related symptoms are not known. This meta-analysis was designed to examine effects of yoga on pre- to postintervention improvements in fatigue among cancer patients. PubMed and PsycINFO were searched for peer-reviewed articles of yoga randomized controlled trials including cancer survivors and reporting at least one fatigue measure. Twenty-nine studies met inclusion criteria (n = 1828 patients). Effect sizes (Hedge's g) were calculated for fatigue, depression, and quality of life. Patient-related and intervention-related characteristics were tested as moderators of outcomes. All statistical tests were two-sided. Yoga practice was associated with a small, statistically significant decrease in fatigue (g = 0.45, P = .013). Yoga type was a statistically significant moderator of this relationship (P = .02). Yoga was associated with a moderate decrease in depression (g = 0.72, P = .007) but was not associated with statistically significant changes in quality of life (P = .48). Session length was a statistically significant moderator of the relationship between yoga and depression (P = .004). Neither timing of treatment (during treatment vs posttreatment) nor clinical characteristics were statistically significant moderators of the effects of yoga on outcomes. The effect of yoga on fatigue and depression was larger when the comparator was a "waitlist" or "usual care" than when the control group was another active treatment (P = .036). Results suggest yoga may be beneficial as a component of treatment for both fatigue and depression in cancer survivors.


Panama: An Open-Source Educational App for Ion Channel Biophysics Simulation.
This article describes an open-source educational software, called Panama, developed using R, that simulates the biophysics of voltage-gated ion channels. It is made publicly available as an R package called Panama and as a web app at http://www.neuronsimulator.com. A need for such a tool was observed after surveying available software packages. Available packages are either not robust enough to simulate multiple ion channels, too complicated, usable only as desktop software, not optimized for mobile devices, not interactive, lack intuitive graphical controls, or not appropriate for educational purposes. This app simulates the physiology of voltage-gated sodium, potassium, and chlorine channels; A channel; M channel; AHP channel; calcium-activated potassium channel; transient-calcium channel; and leak-calcium channel, under current-clamp or voltage-clamp conditions. As the input values on the app are changed, the output can be instantaneously visualized on the web browser and downloaded as a data table to be further analyzed in a spreadsheet program. This app is a first-of-its-kind, mobile-friendly, and touchscreen-friendly online tool that can be used as an installable R package. It has intuitive touch-optimized controls, instantaneous graphical output, and yet is pedagogically robust for educational purposes.


Biochemical and proteomic insights into sarcoplasmic reticulum Ca2+-ATPase complexes in skeletal muscles.
Skeletal muscles contain large numbers of high-molecular-mass protein complexes in elaborate membrane systems. Integral membrane proteins are involved in diverse cellular functions including the regulation of ion handling, membrane homeostasis, energy metabolism and force transmission. The proteomic profiling of membrane proteins and large protein assemblies in skeletal muscles are outlined in this article. This includes a critical overview of the main biochemical separation techniques and the mass spectrometric approaches taken to study membrane proteins. As an illustrative example of an analytically challenging large protein complex, the proteomic detection and characterization of the Ca2+-ATPase of the sarcoplasmic reticulum is discussed. The biological role of this large protein complex during normal muscle functioning, in the context of fiber type diversity and in relation to mechanisms of physiological adaptations and pathophysiological abnormalities is evaluated from a proteomics perspective. Mass spectrometry-based muscle proteomics has decisively advanced the field of basic and applied myology. Although it is technically challenging to study membrane proteins, innovations in protein separation methodology in combination with sensitive mass spectrometry and improved systems bioinformatics has allowed the detailed proteomic detection and characterization of skeletal muscle membrane protein complexes, such as Ca2+-pump proteins of the sarcoplasmic reticulum.


Floral symmetry genes and the origin and maintenance of zygomorphy in a plant-pollinator mutualism.
The evolution of floral zygomorphy is an important innovation in flowering plants and is thought to arise principally from specialization on various insect pollinators. Floral morphology of neotropical Malpighiaceae is distinctive and highly conserved, especially with regard to symmetry, and is thought to be caused by selection by its oil-bee pollinators. We sought to characterize the genetic basis of floral zygomorphy in Malpighiaceae by investigating CYCLOIDEA2-like (CYC2-like) genes, which are required for establishing symmetry in diverse core eudicots. We identified two copies of CYC2-like genes in Malpighiaceae, which resulted from a gene duplication in the common ancestor of the family. A likely role for these loci in the development of floral zygomorphy in Malpighiaceae is demonstrated by the conserved pattern of dorsal gene expression in two distantly related neotropical species, Byrsonima crassifolia and Janusia guaranitica. Further evidence for this function is observed in a Malpighiaceae species that has moved to the paleotropics and experienced coincident shifts in pollinators, floral symmetry, and CYC2-like gene expression. The dorsal expression pat-tern observed in Malpighiaceae contrasts dramatically with their actinomorphic-flowered relatives, Centroplacaceae (Bhesa paniculata) and Elatinaceae (Bergia texana). In particular, B. texana exhibits a previously undescribed pattern of uniform CYC2 expression, suggesting that CYC2 expression among the actinomorphic ancestors of zygomorphic lineages may be much more complex than previously thought. We consider three evolutionary models that may have given rise to this patterning, including the hypothesis that floral zygomorphy in Malpighiaceae arose earlier than standard morphology-based character reconstructions suggest.


The analysis of methods for measurement of methane oxidation in landfills.
Landfills and dumps are important sources of atmospheric methane. There is no generally accepted estimate of the influence of methane oxidation on landfill methane emissions. The present work aimed to analyse different methods for the investigation of methane emission and oxidation in methane-producing environments (wetlands, landfills, sludge checks), and to develop the precise procedure for the landfills. The combination of geochemical and microbiological methods to estimate and monitor the oxidation and emission of methane in landfills during different seasons is proposed. It includes the measurements, both on the surface and at different depths (up to 1 m) of landfill ground of the following parameters: (1) concentrations of methane, carbon dioxide and oxygen; (2) quantity of 13C isotope in gas samples; (3) methane-oxidation activity of landfill grounds assayed with two different methods: (a) in conditions of no moisture or substrate limitations, and (b) in conditions with a minimal deviation to in situ conditions; (4) the density of methanotrophic microbial population.


Conditional intrinsic voltage oscillations in mature vertebrate neurons undergo specific changes in culture.
Although intrinsic neuronal properties in invertebrates are well known to undergo specific adaptive changes in culture, long-term adaptation of similar properties in mature vertebrate neurons remain poorly understood. To investigate this, we used an organotypic slice preparation from the spinal cord of adult turtles maintainable for several weeks in culture conditions. N-methyl-D-aspartate (NMDA)-induced-tetrodotoxin (TTX)-resistant voltage oscillations in motoneurons were approximately 10 times faster in culture than in acute preparations. Oscillations in culture were abolished by NMDA receptor antagonists or by high extracellular Mg2+ concentrations. However, in contrast with results from motoneurons in the acute slice, NMDA-induced oscillations in culture did not depend on CaV1.3 channel activation as they still remained after nifedipine application. Other CaV1.3 channel-mediated properties such as metabotropic receptor-induced oscillations and plateau potentials failed to be induced in culture. This study shows that changes specifically affecting CaV1.3 channel contribution to intrinsic oscillatory property expression may occur in culture. The results contribute also to understanding further the potential for plasticity of mature vertebrate neurons.


Treatment of chickenpox in immunocompromised children.
In Hungary since 1981, 98 immunocompromised children have been treated with intravenous acyclovir for varicella zoster virus infections. They were treated in an open study or a double-blind study. Results of both are discussed briefly. Overall, five of 74 patients with varicella died, whereas all 24 patients with herpes zoster recovered. Treatment failures occurred in patients in whom treatment started late and in those with severe lymphocytopenia. In some children, varicella zoster virus-specific antibodies failed to develop by the end of treatment, and a proportion of these suffered recurrent episodes of varicella.


PARTIAL TOPOGRAPHY-GUIDED PHOTOREFRACTIVE KERATECTOMY FOLLOWED BY CORNEAL CROSS LINKING IN THE MANAGEMENT OF PROGRESSIVE KERATOCONUS: OUR INITIAL TEN-MONTH RESULTS.
The aim was to assess the results achieved in keratoconic corneas submitted to the combined partial topography-guided photorefractive keratectomy (TG-PRK) and corneal cross linking (CXL) procedure performed on the same day. Four patients underwent this treatment of one eye. Corneal epithelium removal was performed by 50-micron phototherapeutic keratectomy. Then, partial TG-PRK laser treatment was applied (Wavelight Allegretto, Eye Q, 400Hz), followed by corneal collagen cross-linking (CXL, 3 mW/cm2) for 30 minutes using 0.1% topical riboflavin solution. Outcome measurements included uncorrected distance visual acuity (UCDVA), best spectacle corrected distance visual acuity (BSCDVA), manifest refraction spherical equivalent, keratometry, corneal high order aberration values, and corneal tomography. At the end of 10-month follow up, all eyes showed improvement in BSCDVA of 1-5 lines on Snellen chart. All other investigated parameters showed significant improvement as well. One eye showed some topographic improvement, but no improvement in UCDVA. No corneal haze, prolonged epithelial healing or endothelial cell loss occurred. During 10-month follow up, the same-day combined TG-PRK and CXL appeared to offer tomographic improvement and better visual acuity in keratoconus patients.


Cytoskeletal role in the transition from compensated to decompensated hypertrophy during adult canine left ventricular pressure overloading.
Increased microtubule density causes cardiocyte contractile dysfunction in right ventricular (RV) pressure-overload hypertrophy, and these linked phenotypic and contractile abnormalities persist and progress during the transition to failure. Although more severe in cells from failing than hypertrophied RVs, the mechanical defects are normalized in each case by microtubule depolymerization. To define the role of increased microtubule density in left ventricular (LV) pressure-overload hypertrophy and failure, in a given LV we examined ventricular mechanics, sarcomere mechanics, and free tubulin and microtubule levels in control dogs and in dogs with aortic stenosis both with LV hypertrophy alone and with initially compensated hypertrophy that had progressed to LV muscle failure. In comparing initial values with those at study 8 weeks later, dogs with hypertrophy alone had a very substantial increase in LV mass but preservation of a normal ejection fraction and mean systolic wall stress. Dogs with hypertrophy and associated failure had a substantial but lesser increase in LV mass and a reduction in ejection fraction, as well as a marked increase in mean systolic wall stress. Cardiocyte contractile function was equivalent, and unaffected by microtubule depolymerization, in cells from control LVs and those with compensated hypertrophy. In contrast, cardiocyte contractile function in cells from failing LVs was quite depressed but was normalized by microtubule depolymerization. Microtubules were increased only in failing LVs. These contractile and cytoskeletal changes, when assayed longitudinally in a given dog by biopsy, appeared in failing ventricles only when wall stress began to increase and function began to decrease. Thus, the microtubule-based cardiocyte contractile dysfunction characteristic of pressure-hypertrophied myocardium, originally described in the RV, obtains equally in the LV but is shown here to have a specific association with increased wall stress.


The role of subunit sialic acid in the thyrotropic and gonadotropic activities of human chorionic gonadotropin.
The present studies were undertaken to delineate the role of sialic acid residues in the two subunits of hCG in relation to its hormonal activity. Sialic acid was removed by treatment of the individual subunits or intact hCG with insolubilized neuraminidase. Desialylated variants of hCG were obtained by combining an asialo subunit (as alpha or as beta) with its complementary intact or desialylated subunit. When tested in the hCG receptor assay using a rat testis fraction, none of the hCG variants exhibited any loss of activity compared with that of intact purified hCG. In in vitro bioassays that employed cAMP and testosterone generation in rat Leydig cells as indices of response, intact hCG and as alpha in combination with intact beta (as alpha-beta) were equipotent. In contrast, intact alpha-subunit combined with as beta (alpha-as beta) and desialylated intact hCG (asialo-hCG) showed activity that at the highest concentration of each tested (20 ng/ml) was no more than half of that evoked by intact hCG. In a TSH receptor assay in human thyroid membranes, loss of sialic acid from either one or both hCG subunits resulted in enhancement of binding affinity; the rank order of decreasing potency was asialo-hCG, alpha-as beta, as alpha-beta. However, despite their enhanced binding affinity, and like intact hCG itself, none of the variants elicited a cAMP response in either human thyroid membranes or cultured human thyroid cells. Rather, asialo-hCG and alpha-as beta, but not intact hCG and as alpha-beta, were effective antagonists of the stimulatory response induced by bovine TSH in thyroid cells. These findings indicate that desialylation of hCG enhances its binding affinity for hCG receptors in testis and, much more so, for TSH receptors in human thyroid. Desialylation also changes hCG from a full agonist to a partial agonist in testis and from a nonagonist to an antagonist in human thyroid. In all cases, sialic acid in the beta-subunit of hCG appears to have a predominant role in these effects.


Decreased SIRT4 protein levels in endometrioid adenocarcinoma tissues are associated with advanced AJCC stage.
Members of the SIRT family are a highly conserved family of NAD+-dependent enzymes, many of which (SIRT1-7) play an important role in tumor formation. Recently, several studies have suggested that SIRT4 not only regulates glutamine metabolism, but also serves as a tumor suppressor. There are no studies have assessed its clinical significance in endometrioid adenocarcinoma. We investigated SIRT4 protein levels in endometrioid adenocarcinoma and its possible association with selected clinico-pathological parameters by immunohistochemical staining of a tissue microarray that included 65 endometrioid adenocarcinoma patients. SIRT4 protein levels in endometrioid adenocarcinoma were markedly lower than its non-neoplastic tissue counterpart (P< 0.001). Moreover, lower SIRT4 expression levels were observed in advanced AJCC stages of development (P= 0.002). Our results indicated that SIRT4 may be involved in the development of endometrioid adenocarcinoma and is a promising target for both the diagnosis and potential therapy of endometrioid adenocarcinoma.


Amino acid abnormalities in cerebrospinal fluid of patients with parkinsonism and extrapyramidal disorders.
Free amino acid determinations in the cerebrospinal fluid of patients with Parkinson's disease or other extrapyramidal disorders showed that in both groups most amino acids were increased. Significantly increased amino acids were neutral and basic amino acids. Amino acid clusters were present and corresponded with the grouping of amino acids in accordance with amino acid transport systems. The amino acids within the clusters showed a remarkable degree of correlation, and there was a notable correlation between the clusters both in the parkinsonian group and in the group of extrapyramidal disorders, but not in a control group. Our data suggest that in a number of extrapyramidal disorders, Parkinson's disease included, a more generalized abnormality exists than neuronal loss only and, in addition, that patients with these neurologic conditions have a common biochemical defect in their amino acid transport systems.


An occupational health approach to anaesthetic air pollution.
The principles of occupational health practice as applicable to operating theatre staff are stated. Operating theatre air was samples for halothane at three Sydney hospitals--one in which a scavenging system was in operation and two without such a system. A method giving time-weighted average concentrations over the period of sampling was used. Anaesthetic techniques varied for adults and children. The scavenging system was found to be highly efficient. Less than 0.1 ppm of halothane was found in the air of one theatre in which a flow rate of 4 litres per minute with 0.5% halothane and controlled ventilation were being used for routine anaesthetics in adults. In another theatre in which paediatric surgery was being performed, the anaesthetic technique utilized a flow rate of 6 litres per minute with 0.5% halothane and a T-piece, and the air was found to contain 0.8 ppm of halothane. Concentrations of up to 8 ppm were found in unscavenged theatres. Other possible occupational hazards of the environment, such as exposure to X-rays, viral infection and aerosol sprays, are mentioned. These may be significant.


Accurate double many-body expansion potential energy surface for triplet H3+. II. The upper adiabatic sheet (2(3)A').
We report on a global potential energy hypersurface for the upper sheet of the lowest triplet state of H3+. The analytic representation is based on the double many-body expansion theory. The ab initio data points, calculated with a large cc-pV5Z basis, are represented with a root mean square deviation of only 5.54 cm(-1) in the energy region below the H(+)+2H(2S) dissociation threshold. The quasi-bound vibronic states supported by this surface have also been calculated.


Aurora B prevents aneuploidy via MAD2 during the first mitotic cleavage in oxidatively damaged embryos.
A high rate of chromosome aneuploidy is exhibited in in vitro fertilization (IVF)-derived embryos. Our previous experiments suggested that reactive oxygen species (ROS) can activate Mad2, a key protein in the spindle assembly checkpoint (SAC), and delay the first mitotic, providing time to prevent the formation of embryonic aneuploidy. We aimed to determine whether mitotic kinase Aurora B was involved in the SAC function to prevent aneuploidy in IVF-derived embryos. We analysed aneuploidy formation and repair during embryo pre-implantation via 4',6-diamidino-2-phenylindole (DAPI) staining and karyotype analysis. We assessed Aurora B activation by immunofluorescence and investigated the effect of Aurora B inhibition on embryo injury-related variables, such as embryonic development, ROS levels, mitochondrial membrane potential and γH2AX-positive expression. We observed the expression and phosphorylation of Thr232 in Aurora B in oxidative stress-induced zygotes. Moreover, inhibition of Aurora B caused chromosome mis-segregation, abnormal spindle structures, abnormal chromosome number and reduced expression of Mad2 in IVF embryos. Our results suggest that Aurora B causes mitotic arrest and participates in SAC via Mad2 and H3S10P, which is required for self-correction of aneuploidies. We demonstrate here that oxidative stress-induced DNA damage triggers Aurora B-mediated activation of SAC, which prevents aneuploidy at the first mitotic cleavage in early mouse IVF embryos.


Comparative assessment of blood and urine analyses in patients with acute poisonings by medical, narcotic substances and alcohol in clinical toxicology.
Acute poisonings by medical, narcotic substances and alcohol are actual in Russia in the recent years. Comparison of analytic facilities of modern analytical techniques: chromatographic (HPLC, GC, GC-MS) and immuno-chemical (FPIA) in clinical toxicology for urgent diagnostics, assessment of the severity of acute poisoning and the efficacy of the treatment in patients with acute poisonings by psychotropic drugs, narcotics and alcohol have been done. The object of the study were serum, blood, urine of 611 patients with acute poisonings by amitriptyline, clozapine, carbamazepine, opiates and also alcohol. Threshold concentrations (threshold, critical and lethal) of the toxicants and their active metabolites which corresponded to different degrees of poisoning severity have been determined. The most comfortable and informative screening method for express diagnostics and assessment of severity of acute poisonings by psychotropic drugs and narcotics showed the HPLC with using automatic analyzers. FPIA using the automatic analyzer could be applied for screening studies, if group identification is enough. GC-FID method is advisable in case of poisoning by medical substances and narcotics in view of repeated investigation for assessment of the efficacy of the therapy. GC-MS could be advisable for confirming the results of other methods. GC-TCD possess high sensitivity and specificity and is optimal for express differential diagnostics and quantitative assessment of acute poisoning by ethanol and other alcohols.


Plausible Roles for RAGE in Conditions Exacerbated by Direct and Indirect (Secondhand) Smoke Exposure.
Approximately 1 billion people smoke worldwide, and the burden placed on society by primary and secondhand smokers is expected to increase. Smoking is the leading risk factor for myriad health complications stemming from diverse pathogenic programs. First- and second-hand cigarette smoke contains thousands of constituents, including several carcinogens and cytotoxic chemicals that orchestrate chronic inflammatory responses and destructive remodeling events. In the current review, we outline details related to compromised pulmonary and systemic conditions related to smoke exposure. Specifically, data are discussed relative to impaired lung physiology, cancer mechanisms, maternal-fetal complications, cardiometabolic, and joint disorders in the context of smoke exposure exacerbations. As a general unifying mechanism, the receptor for advanced glycation end-products (RAGE) and its signaling axis is increasingly considered central to smoke-related pathogenesis. RAGE is a multi-ligand cell surface receptor whose expression increases following cigarette smoke exposure. RAGE signaling participates in the underpinning of inflammatory mechanisms mediated by requisite cytokines, chemokines, and remodeling enzymes. Understanding the biological contributions of RAGE during cigarette smoke-induced inflammation may provide critically important insight into the pathology of lung disease and systemic complications that combine during the demise of those exposed.