Feasibility and acceptability of a proposed pharmacy-based harm reduction intervention to reduce opioid overdose, HIV and hepatitis C.
Evidence-based harm reduction intervention components which might benefit pharmacy patients have not been integrated and studied. To investigate the feasibility and acceptability of a proposed pharmacy-based harm reduction intervention to reduce opioid overdose, HIV and hepatitis C called PharmNet. Indiana managing pharmacists were surveyed in 2018 to assess the feasibility and acceptability of an intervention for opioid misuse screening, brief intervention, syringe and naloxone dispensing, and referrals provision. The Consolidated Framework for Implementation Research informed the survey development and analysis. The sample included 303 (30.8%) pharmacists; 215 (70.9%) provided detailed written comments. Intervention Characteristics: 83.3% believed PharmNet would benefit patients, and that staff could deliver the intervention with adequate training (70.0%). Inner Setting: While 77.2% believed their pharmacy culture supported practice change, 57.5% of chain pharmacists believed their pharmacies would not have time for PharmNet. Outer Setting: 73.3% believed additional addiction and overdose screening is needed in their community, and pharmacies should offer new services to help reduce opioid overdose and addiction among their patients (79.5%). A vast majority (97.7%) were asked by patients in the past 2 years about syringe related issues; 67.7% were asked about syringes for non-prescription injection drug use. Individuals Involved: While 62.4% believed PharmNet was within pharmacy scope of practice and 90.1% were comfortable consulting about syringe use, pharmacists reported that they had limited control over the implementation environment. 38.0% of pharmacists indicated interest in advising the development of PharmNet. An implementation trial of a modified version of PharmNet is likely feasible; yet will be challenged by structural pressures particularly in chain pharmacies. Successful implementation will involve the development of resources and policy components to manage outer and inner setting characteristics and align the intervention to the implementation environment.


Induction of tolerance in murine autoimmune diabetes by transient blockade of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway.
The present study demonstrated that a short-term administration of mAbs against leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) at critical periods resulted in complete protection of autoimmune diabetes in non-obese diabetic (NOD) mice. When these mAbs were administered for only 6 days at 2 wk of age, neither diabetes nor insulitis was observed at 30 wk of age. It appears that the tolerance against beta cell Ag(s) was induced by this transient blockade of the LFA-1/ICAM-1 pathway. Protective suppressor activity was not enough to prevent diabetes because co-transfer of splenocytes from female NOD mice, which had received these mAbs at 2 wk of age, resulted in only a short delay of the diabetic onset caused by adoptive transfer of splenocytes from acutely diabetic NOD mice. Transfer of these splenocytes to young NOD mice could not also abrogate the spontaneous diabetes and insulitis. Furthermore, cyclophosphamide treatment could not abrogate the protection. When splenocytes from the treated NOD mice were transferred to NOD-SCID mice, none of the recipient mice developed significant insulitis and subsequent overt diabetes, suggesting the absence or the inactivation of diabetogenic effector T cells. However, splenic T cells from the insulitis-free NOD mice that had received the mAb treatment preserved proliferative responses to both islet cells and 65-kDa glutamic acid decarboxylase (GAD65) in vitro. These results suggest that a unique peripheral tolerance was induced by the transient blockade of the LFA-1/ICAM-1 pathway in an early age of NOD mice.


Accelerating adaptive inverse distance weighting interpolation algorithm on a graphics processing unit.
This paper focuses on designing and implementing parallel adaptive inverse distance weighting (AIDW) interpolation algorithms by using the graphics processing unit (GPU). The AIDW is an improved version of the standard IDW, which can adaptively determine the power parameter according to the data points' spatial distribution pattern and achieve more accurate predictions than those predicted by IDW. In this paper, we first present two versions of the GPU-accelerated AIDW, i.e. the naive version without profiting from the shared memory and the tiled version taking advantage of the shared memory. We also implement the naive version and the tiled version using two data layouts, structure of arrays and array of aligned structures, on both single and double precision. We then evaluate the performance of parallel AIDW by comparing it with its corresponding serial algorithm on three different machines equipped with the GPUs GT730M, M5000 and K40c. The experimental results indicate that: (i) there is no significant difference in the computational efficiency when different data layouts are employed; (ii) the tiled version is always slightly faster than the naive version; and (iii) on single precision the achieved speed-up can be up to 763 (on the GPU M5000), while on double precision the obtained highest speed-up is 197 (on the GPU K40c). To benefit the community, all source code and testing data related to the presented parallel AIDW algorithm are publicly available.


Comparative study of 3 exophthalmometers and computed tomographic biometry.
Accurate and reproducible exophthalmometry is mandatory to diagnose and follow-up orbital patients, especially in Graves disease. However, many variations are described among the different commercially available exophthalmometers. Sixty patients, who underwent a cerebral computed tomography (CT) scan, were included. External prebicanthal segments (EPBCS) for right and left eyes (RE and LE), interorbital distance, and globe axial length were recorded by a first observer (O1), more experienced than a second (O2). Intraobserver and interobserver reproducibility were evaluated, using intraclass correlation coefficient (ICC) and Bland and Altman plots. Concordance between each EPBCS measurement for each eye and CT scan biometry was moderate for the Luedde ruler for the 2 observers. For the Hertel exophthalmometer, concordance was moderate for O1 in the 2 eyes and moderate in RE but good in LE for O2. For the Mourits exophthalmometer, this concordance was very good in RE and good in LE for O1, and good whatever the eye for O2. Intraobserver (ICC varying from 0.75 to 0.95 for the 2 observers) and interobserver (ICC from 0.69 to 0.94) reproducibility were high, especially for the Mourits exophthalmometer. Bland and Altman plots showed underestimations when using the Luedde ruler, overestimations when using the Hertel exophthalmometer, and overestimation of small values and underestimation of high values when using the Mourits exophthalmometer when compared to CT scan biometry. We demonstrated great accuracy to CT scan biometry with 1-prism Mourits exophthalmometer, low accuracy with the Luedde instrument, and intermediate accuracy with the Hertel exophthalmometer, with fair intraobserver and interobserver reproducibility.


Contrasting effects of phosphatidylinositol- and phosphatidylcholine-specific phospholipase C on apoptosis in cultured endothelial cells.
In the authors' previous studies, they found that phosphatidylcholine-specific phospholipase C (PC-PLC) and phosphatidylinositol-specific phospholipase C (PI-PLC) played contrary roles in the apoptosis of vascular endothelial cells (VECs), but the mechanism underlying the phenomenon remains unclear. To address this question, in this study, the authors investigated the changes of cell cycle distribution, the expression of P53, and the phosphorylation of Akt when PI-PLC was inhibited by its specific inhibitor compound 48/80, and they also examined the phosphorylation of Akt when VEC apoptosis was inhibited by D609, a specific inhibitor of PC-PLC. The results showed that suppression of PI-PLC promoted VEC apoptosis by inhibiting Akt phosphorylation, elevating P53 expression, and affecting the cell cycle distribution. Contrarily, suppression of PC-PLC promoted the phosphorylation of Akt. The data suggested that PI-PLC and PC-PLC might control the apoptosis by jointly regulating Akt phosphorylation, P53 expression, and affecting cell cycle in VECs.


[Cavernous hemangioma of the colon. Case report and review of the literature].
Colon and rectum hemangioma is a rare disease, and even more so when it presents as cavernous subtype; few of these hemangioma have been confirmed by pathology reports. The main presentation of this disease is observed by transrectal painless bleeding; other manifestations are less frequent. Diagnosis implies high index of suspicion and proper diagnostic workup; this entity has been frequently misdiagnosed as other more common entities. We present the case of a 15-year-old female patient with a cavernous hemangioma of the sigmoid colon; her principal complaint was abdominal pain. Diagnosis was suspected due to the finding of phleboliths in plain abdominal film and diagnostic findings in colonoscopy. The patient was treated by means of segmental resection of the colon and experienced a satisfactory postoperatory recovery. According to the literature, these hemangiomas originate from embryologic sequestrations of mesodermal tissue, while clinically they usually present between the ages of 5 and 25 years, most commonly with painless transrectal bleeding and less frequently with intestinal obstruction, tenesmus, urgency, abdominal pain or mass, and anemia. The majority of these hemangiomas are localized in rectosigmoid region of the colon and may infiltrate surrounding tissues; 26-50% show phleboliths in plain abdominal film. Colonoscopy is considered by many authors the best diagnostic tool; angiography, computed tomography (CT) scan and scintigraphy may be also useful. The only effective treatment of this disease is complete surgical resection, for which there have been many proposals regarding best method and approach.


Water redistribution determines photosynthetic responses to warming and drying in two polar mosses.
Predicting impacts of climate change requires an understanding of the sensitivity of species to temperature, including conflated changes in humidity. Physiological responses to temperature and clump-to-air vapour pressure difference (VPD) were compared in two Antarctic moss species, Ceratodon purpureus (Hedw.) Brid. and Schistidium antarctici (Cardot) L.I. Savicz & Smirnova. Temperatures from 8 to 24°C had no significant effects on photosynthesis or recovery from drying, whereas high VPD accelerated drying. In Schistidium, which lacks internal conduction structures, shoots dried more slowly than the clump, and photosynthesis ceased at high shoot relative water content (RWC), behaviour consistent with a strategy of drought avoidance although desiccation tolerant. In contrast, shoots of Ceratodon have a central vascular core, but dried more rapidly than the clump. These results imply that cavitation of the hydroid strand enables hydraulic isolation of extremities during rapid drying, effectively slowing water loss from the clump. Ceratodon maintained photosynthetic activity during drying to lower shoot RWC than Schistidium, consistent with a strategy of drought tolerance. These ecophysiological characteristics may provide a functional explanation for the differential distribution of Schistidium and Ceratodon along moisture gradients in Antarctica. Thus, predicting responses of non-vascular vegetation to climate change at high latitudes requires greater focus on VPD and hydraulics than temperature.


Hearing rehabilitation with Baha® transcutaneous and percutaneous systems.
Longitudinally verify the influence of auditory tonal thresholds obtained with transcutaneous and percutaneous bone-anchored hearing aids on speech perception in individuals with external and/or middle ear malformation and chronic otitis media. Observational, retrospective, longitudinal follow-up study of 30 unilateral users of the transcutaneous and percutaneous Baha® system for the collection of secondary data on pure tone thresholds obtained through free field audiometry and sentence recognition threshold in silence and noise in conditions: without the prosthesis; at the time of activation; in the first month of use (post 1); and in the third month (post 2). There was a significant difference between pure tone thresholds obtained at frequencies of 3 and 4kHz with better results for the percutaneous technique at all evaluation moments. For both systems, better performance was observed in sentence recognition in silence and in noise, with a significant difference in activation (p<0.001), but it remained stable during the other evaluation moments. The percutaneous system showed better benefit in recognizing sentences in noise only on activation (p=0.036), when compared to the transcutaneous system. The percutaneous system provided better audibility for high frequencies; however, such audibility did not influence sentence recognition in the silent situation for both systems. For the noise situation, better responses were observed in the percutaneous system, however, the difference was not maintained over time.


The diaphragmatic compound muscle action potentials (DCMAPs) at different lung volumes--a prospective electrophysiological study of the respiratory system.
Phrenic nerve conduction study and measurements of static lung volumes such as functional residual capacity (FRC), total lung capacity (TLC) and residual volumes (RV) using body plethysmography were carried out in 31 normal healthy male subjects (31 +/- 8 years). The objective was to correlate changes in latency, amplitude, duration and area of diaphragmatic compound muscle action potential (DCMAPs) with lung volumes and changes in them with changes in postures. The mean phrenic nerve latency did not show any significant change with lung volumes or postures, but the latency and height of the subject had a significant correlationship (r = 0.68). The peak to peak amplitude of DCMAP showed a significant relationship with the quantitative lung volumes (r = 0.65). The amplitude was significantly higher and duration reduced (p < 0.001) at TLC as compared with those at measured FRC and RV in both sitting and supine postures. The area under the curve did not change significantly. Similarly, amplitudes and latency did not show any significant relation with other anthropometric parameters. The study evaluates a new quantitative relationship between DCMAPs amplitude and lung volumes. This may be carefully used along with other clinical parameters in critically ill patients for an early weaning from ventilator. Posture exerts minimal influence on DCMAPs amplitude; since DCMAPs amplitudes depends on the position of the diaphragm which in turn depends on dipolic potential, its electromagnetic fields and its moving angle subtends at the recording electrode, one can confidently use it to predict lung volume in respiratory failure due to neuromuscular diseases where subjective lung function assessment is impossible. However, a further study is in process in the critical care unit to confirm its utility.


Liver Disease in Patients After the Fontan Operation.
We reviewed records of all patients with an initial Fontan operation or revision from 1973 to 2012 at our institution (n = 1,138); 195 patients had postoperative liver data available. Cirrhosis was identified by histopathology or characteristic findings on imaging with an associated diagnosis of cirrhosis by a hepatologist. Of 195 patients with biopsy or imaging, 10-, 20-, and 30-year freedom from cirrhosis was 99%, 94%, and 57%, respectively. There were 40 of 195 patients (21%) diagnosed with cirrhosis (mean age at Fontan 10.7 ± 8 years). On multivariate analysis, hypoplastic left heart syndrome was associated with increased risk of cirrhosis (n = 2 of 16, p = 0.0133), whereas preoperative sinus rhythm was protective (p = 0.009). Survival after diagnosis of cirrhosis was 57% and 35%, at 1, and 5 years, respectively. The cause of death was known for 9 patients (5 multiorgan failure, 2 liver failure, and 2 heart failure). In conclusion, there is an incremental occurrence of cirrhosis after the Fontan, which should be considered when designing follow-up protocols for patients after Fontan operation.


Parvalbumin-immunoreactive neurons in the hippocampal formation of Alzheimer's diseased brain.
The number and topographic distribution of immunocytochemically stained parvalbumin interneurons was determined in the hippocampal formation of control and Alzheimer's diseased brain. In control hippocampus, parvalbumin interneurons were aspiny and pleomorphic, with extensive dendritic arbors. In dentate gyrus, parvalbumin cells, as well as a dense plexus of fibers and puncta, were associated with the granule cell layer. A few cells also occupied the molecular layer. In strata oriens and pyramidale of CA1-CA3 subfields, parvalbumin neurons gave rise to dendrites that extended into adjacent strata. Densely stained puncta and beaded fibers occupied stratum pyramidale, with less dense staining in adjacent strata oriens and radiatum. Virtually no parvalbumin profiles were observed in stratum lacunosum-moleculare or the alveus. Numerous polymorphic parvalbumin neurons and a dense plexus of fibers and puncta characterized the deep layer of the subiculum and the lamina principalis externa of the presubiculum. In Alzheimer's diseased hippocampus, there was an approximate 60% decrease in the number of parvalbumin interneurons in the dentate gyrus/CA4 subfield (P<0.01) and subfields CA1-CA2 (P<0.01). In contrast, parvalbumin neurons did not statistically decline in subfields CA3, subiculum or presubiculum in Alzheimer's diseased brains relative to controls. Concurrent staining with Thioflavin-S histochemistry did not reveal degenerative changes within parvalbumin-stained profiles. These findings reveal that parvalbumin interneurons within specific hippocampal subfields are selectively vulnerable in Alzheimer's disease. This vulnerability may be related to their differential connectivity, e.g., those regions connectionally related to the cerebral cortex (dentate gyrus and CA1) are more vulnerable than those regions connectionally related to subcortical loci (subiculum and presubiculum).


Current status of prophylaxis of retinal detachment.
Our indications for prophylaxis may be summarized as follows: (1) All symptomatic holes. (2) All holes in aphakic eye. (3) All holes in fellow eyes. (4) Lattice degeneration in fellow eyes, even when holes are not present. (5) Holes in snail-track degeneration. (6) The fellow eye of one with a giant tear. (7) Asymptomatic holes in myopic eyes except those within the vitreous base. (8) Some large asymptomatic holes in non-fellow or aphakic eyes.


A program of operative angioplasty: endovascular intervention and the vascular surgeon.
Vascular surgeons are ideally suited to select and perform endovascular interventions either as primary therapy or as an adjunct to bypass surgery. Attaining proficiency in endovascular techniques is an important goal in the training of vascular surgeons. We report our initial experience with a program of endovascular intervention performed in the operating room by vascular surgeons. During the previous three years, we performed 109 angioplasty procedures, 60 aortoiliac (55%), 32 femoropopliteal (29%), and 17 popliteal/tibial (16%), using guidewires and angioplasty balloons directed by intraoperative digital subtraction C-arm arteriography with road-mapping capabilities. Indications for angioplasty included disabling claudication in 59 patients (54%), rest pain in 18 (17%), and tissue loss in 32 (29%). Angioplasty was accompanied by stent placement in 39 of 60 aortoiliac procedures (65%) and in two of 32 femoral procedures (6%). In 16 cases (15%), the endovascular procedure was performed in conjunction with a bypass procedure. In selected cases (15, 14%), duplex scanning was the sole diagnostic method used before surgery to identify the lesion, eliminating the need for preoperative arteriographic scans. Segmental pressure measurements, duplex ultrasound scans, and treadmill exercise testing as indicated were performed before and after surgery. The efficacy of the endovascular intervention was assessed at 3-month intervals during the first year and at 6-month intervals thereafter. A successful results was defined using criteria recommended by the Ad Hoc Subcommittee on Reporting Standards for Endovascular Procedures from the Society for Vascular Surgery/International Society for Cardiovascular Surgery. This included the combination of symptomatic improvement, obtaining an anatomically successful result with < 30% residual lumen stenosis, and elimination of the translesion gradient with an improvement in high thigh-brachial index or ankle-brachial index greater than 0.15. Initial success was achieved in 55 of 60 aortoiliac (92%), 28 of 32 femoropopliteal (88%), and 16 of 17 popliteal/tibial (94%) angioplasty procedures. Clinical follow-up has been achieved in all cases, with continued clinical success rates of 80%, 75%, and 82% for aortoiliac, femoropopliteal, and popliteal/tibial angioplasty procedures, respectively, with a mean follow-up of 15.7 months. These results confirm the value of a program in which C-arm technology was used by vascular surgeons in the performance of angioplasty and stenting procedures in the operating room. This experience in therapeutic endovascular intervention will facilitate the credentialing process for future vascular surgeons.


Predicting EEG Responses to Attended Speech via Deep Neural Networks for Speech.
Attending to the speech stream of interest in multi-talker environments can be a challenging task, particularly for listeners with hearing impairment. Research suggests that neural responses assessed with electroencephalography (EEG) are modulated by listener's auditory attention, revealing selective neural tracking (NT) of the attended speech. NT methods mostly rely on hand-engineered acoustic and linguistic speech features to predict the neural response. Only recently, deep neural network (DNN) models without specific linguistic information have been used to extract speech features for NT, demonstrating that speech features in hierarchical DNN layers can predict neural responses throughout the auditory pathway. In this study, we go one step further to investigate the suitability of similar DNN models for speech to predict neural responses to competing speech observed in EEG. We recorded EEG data using a 64-channel acquisition system from 17 listeners with normal hearing instructed to attend to one of two competing talkers. Our data revealed that EEG responses are significantly better predicted by DNN-extracted speech features than by hand-engineered acoustic features. Furthermore, analysis of hierarchical DNN layers showed that early layers yielded the highest predictions. Moreover, we found a significant increase in auditory attention classification accuracies with the use of DNN-extracted speech features over the use of hand-engineered acoustic features. These findings open a new avenue for development of new NT measures to evaluate and further advance hearing technology.


Farmers' perceptions of climate change and agricultural adaptation strategies in rural Sahel.
Farmers in the Sahel have always been facing climatic variability at intra- and inter-annual and decadal time scales. While coping and adaptation strategies have traditionally included crop diversification, mobility, livelihood diversification, and migration, singling out climate as a direct driver of changes is not so simple. Using focus group interviews and a household survey, this study analyzes the perceptions of climate change and the strategies for coping and adaptation by sedentary farmers in the savanna zone of central Senegal. Households are aware of climate variability and identify wind and occasional excess rainfall as the most destructive climate factors. Households attribute poor livestock health, reduced crop yields and a range of other problems to climate factors, especially wind. However, when questions on land use and livelihood change are not asked directly in a climate context, households and groups assign economic, political, and social rather than climate factors as the main reasons for change. It is concluded that the communities studied have a high awareness of climate issues, but climatic narratives are likely to influence responses when questions mention climate. Change in land use and livelihood strategies is driven by adaptation to a range of factors of which climate appears not to be the most important. Implications for policy-making on agricultural and economic development will be to focus on providing flexible options rather than specific solutions to uncertain climate.


Temporal features of size constancy for perception and action in a real-world setting: A combined EEG-kinematics study.
A stable representation of object size, in spite of continuous variations in retinal input due to changes in viewing distance, is critical for perceiving and acting in a real 3D world. In fact, our perceptual and visuo-motor systems exhibit size and grip constancies in order to compensate for the natural shrinkage of the retinal image with increased distance. The neural basis of this size-distance scaling remains largely unknown, although multiple lines of evidence suggest that size-constancy operations might take place remarkably early, already at the level of the primary visual cortex. In this study, we examined for the first time the temporal dynamics of size constancy during perception and action by using a combined measurement of event-related potentials (ERPs) and kinematics. Participants were asked to maintain their gaze steadily on a fixation point and perform either a manual estimation or a grasping task towards disks of different sizes placed at different distances. Importantly, the physical size of the target was scaled with distance to yield a constant retinal angle. Meanwhile, we recorded EEG data from 64 scalp electrodes and hand movements with a motion capture system. We focused on the first positive-going visual evoked component peaking at approximately 90 ms after stimulus onset. We found earlier latencies and greater amplitudes in response to bigger than smaller disks of matched retinal size, regardless of the task. In line with the ERP results, manual estimates and peak grip apertures were larger for the bigger targets. We also found task-related differences at later stages of processing from a cluster of central electrodes, whereby the mean amplitude of the P2 component was greater for manual estimation than grasping. Taken together, these findings provide novel evidence that size constancy for real objects at real distances occurs at the earliest cortical stages and that early visual processing does not change as a function of task demands.


Women's strategies to achieve access to healthcare in Ontario, Canada: a meta-synthesis.
As part of a mixed methods study on women's access to the healthcare system in Ontario, Canada, we undertook a qualitative meta-synthesis to better understand the contextual conditions under which women access healthcare. An earlier phase of the synthesis demonstrated a series of factors that complicate women's access to healthcare in Ontario. Here, we consider women's agency in responding to these factors. We used meta-study methods to synthesise findings from qualitative studies published between January 2002 and December 2010. Studies were identified by searches of numerous databases, including CINAHL, MEDLINE, Scopus, Gender Studies Database and LGBT Life. Inclusion criteria included use of a qualitative research design; published in a peer-reviewed journal during the specified time period; included a sample at least partially recruited in Ontario; included distinct findings for women participants; and in English language. Studies were included in the final sample after appraisals using a qualitative research appraisal tool. We found that women utilised a spectrum of responses to forces limiting access to healthcare: mobilising financial, social and interpersonal resources; living out shortfalls by making do, doing without, and emotional self-management; and avoiding illness and maintaining health. Across the studies, women described their efforts to overcome challenges to accessing healthcare. However, there were evident limits to women's agency and many of their strategies represented temporary measures rather than viable long-term solutions. While women can be resourceful and resilient in overcoming access disparities, systemic problems still need to be addressed. Women need to be involved in designing and implementing interventions to improve access to healthcare, and to address the root problems of these issues.


What cervical screening is appropriate for women who have been vaccinated against high risk HPV? A simulation study.
Women vaccinated against HPV16/18 are approaching the age for cervical screening; however, an updated screening algorithm has not been agreed. We use a microsimulation model calibrated to real published data to determine the appropriate screening intensity for vaccinated women. Natural histories in the absence of vaccination were simulated for 300,000 women using 10,000 sets of transition probabilities. Vaccination with (i) 100% efficacy against HPV16/18, (ii) 15% cross-protection, (iii) 22% cross-protection, (iv) waning vaccine efficacy and (v) 100% efficacy against HPV16/18/31/33/45/52/58 was added, as were a range of screening scenarios appropriate to the UK. To benchmark cost-benefits of screening for vaccinated women, we evaluated the proportion of cancers prevented per additional screen (incremental benefit) of current cytology and likely HPV screening scenarios in unvaccinated women. Slightly more cancers are prevented through vaccination with no screening (70.3%, 95% CR: 65.1-75.5) than realistic compliance to the current UK screening programme in the absence of vaccination (64.3%, 95% CR: 61.3-66.8). In unvaccinated women, when switching to HPV primary testing, there is no loss in effectiveness when doubling the screening interval. Benchmarking supports screening scenarios with incremental benefits of ≥2.0%, and rejects scenarios with incremental benefits ≤0.9%. In HPV16/18-vaccinated women, the incremental benefit of offering a third lifetime screen was at most 3.3% (95% CR: 2.2-4.5), with an incremental benefit of 1.3% (-0.3-2.8) for a fourth screen. For HPV16/18/31/33/45/52/58-vaccinated women, two lifetime screens are supported. It is important to know women's vaccination status; in these simulations, HPV16/18-vaccinated women require three lifetime screens, HPV16/18/31/33/45/52/58-vaccinated women require two lifetime screens, yet unvaccinated women require seven lifetime screens.


A straightforward treatment of activity in aqueous CaCO3 solutions and the consequences for nucleation theory.
The aqueous calcium carbonate system is rigorously investigated with respect to ionic activity. Ideal treatment is found to be a good approximation at relevant concentrations. The data further show that bound CaCO3 species cannot be regarded as "inactive" during nucleation but rather appear to play a key role in the phase-separation process, and that amorphous calcium carbonate (ACC) can be precipitated from much lower levels of supersaturation than previously believed.


Effects of light curing method and exposure time on mechanical properties of resin based dental materials.
The aim of this study was to investigate microhardness and compressive strength of composite resin (Tetric-Ceram, Ivoclar Vivadent), compomer (Compoglass, Ivoclar, Vivadent), and resin modified glass ionomer cement (Fuji II LC, GC Corp) polymerized using halogen light (Optilux 501, Demetron, Kerr) and LED (Bluephase C5, Ivoclar Vivadent) for different curing times. Samples were placed in disc shaped plastic molds with uniform size of 5 mm diameter and 2 mm in thickness for surface microhardness test and placed in a diameter of 4 mm and a length of 2 mm teflon cylinders for compressive strength test. For each subgroup, 20 samples for microhardness (n=180) and 5 samples for compressive strength were prepared (n=45). In group 1, samples were polymerized using halogen light source for 40 seconds; in group 2 and 3 samples were polymerized using LED light source for 20 seconds and 40 seconds respectively. All data were analyzed by two way analysis of ANOVA and Tukey's post-hoc tests. Same exposure time of 40 seconds with a low intensity LED was found similar or more efficient than a high intensity halogen light unit (P>.05), however application of LED for 20 seconds was found less efficient than 40 seconds curing time (P=.03). It is important to increase the light curing time and use appropriate light curing devices to polymerize resin composite in deep cavities to maximize the hardness and compressive strength of restorative materials.


Effect of heat stress on physiological parameters and blood composition in Polish Merino rams.
The Merino sheep represents the most prevalent sheep breed in Poland and is one of the most genetic-stable sheep races. Therefore, the aim of the study was to determine the responses of Polish Merino sheep to three thermal conditions: thermoneutral (16.5 degrees C, group I), mild heat stress (30 degrees C, group II), and severe heat stress (50 degrees C, group III). During the experiment heart rate (HR; beats/min), respiratory rate (RR; breaths/min), rectal temperature (RT) and skin temperatures (ST) were measured daily. The ST measured at four points of the animal body was mostly statistically different (p < 0.01) between the treatment groups. It was found that the highest HR occurred in group II (30 degrees C), and that it was higher than in groups I (16.5 degrees C) and III (50 degrees C) (p < 0.01 for groups I, III). The RR was different (p < 0.01) in all experimental groups (I, II, III) with the highest increase in group II. There was also a clear and significant (p < 0.01) increase in RT during the heat stress phases. Blood analysis including morphology, biochemistry and hormones (adrenaline, noradrenaline, ACTH, and cortisol) was also performed. Significant differences in cortisol level in group II (p < 0.01) and group III (p < 0.05) were observed. There was an upward trend in adrenaline and ACTH as a result of increasing temperature. Differences in noradrenaline levels (p <0.01), with the highest level recorded in group III, were also observed. Additionally there was a strong upward trend in blood parameters, especially in hormone concentrations (cortisol, noradrenaline).


Transferrin-mediated uptake of plutonium by spermatogenic tubules.
Using isolated rat seminiferous tubules as an in vitro model, we have found that 238Pu can cross the blood-tubule barrier and accumulate within tubules in a time dependent manner. Furthermore, similar to 59Fe, tubule 238Pu uptake was inhibited by the addition of excess transferrin, suggesting that plutonium may utilize the physiological iron-transferrin pathway to cross the blood-tubule barrier. However unlike 59Fe, 238Pu was only transiently associated with the tubules, suggesting differences in the intracellular processing of these radionuclides. The assumptions made in the estimation of doses to the human testis from incorporated plutonium are considered.


Consensus Protocol for the Treatment of Super-Refractory Status Epilepticus.
Super-refractory status epilepticus is defined as status epilepticus that persists or recurs 24 hours after anaesthetic therapy onset or after its withdrawal. It is mostly found in intensive care units and carries high mortality but good long-term prognosis for those who survive. In contrast with the initial phases of status epilepticus, treatment lacks strong scientific evidence and is mostly derived from case reports or small case series. To propose a protocol for the treatment of super-refractory status epilepticus in level III intensive care units, focusing on the treatment strategies to control clinical and/or electroencephalographic epileptic activity. Narrative review of the literature by PubMed search. Available evidence was discussed in consensus meetings by intensive care and neurology experts' from a level III intensive care unit and one of the Portuguese reference centres for the treatment of refractory epilepsy, respectively. Anaesthetics with the highest level of evidence are propofol, midazolam, thiopental and ketamine. These represent the basis of the treatment of super-refractory status epilepticus and should be used in combination with antiepileptic drugs. The level of evidence for the latter is lower, however, levetiracetam, topiramate, pregabalin, lacosamide, valproic acid, phenytoin and perampanel may be recommended. Alternative therapeutic strategies with very low level of evidence are recommended in cases of total absence of clinical response, such as magnesium sulphate, pyridoxine, ketogenic diet, therapeutic hypothermia and immunosupression. We propose a treatment protocol based on a sequential combination of anaesthetics, anti-epileptic drugs and alternative therapies. Strategies to evaluate treatment response and to wean drugs based on clinical results are also proposed.


One-dimensional surface phonon polaritons in boron nitride nanotubes.
Surface polaritons, which are electromagnetic waves coupled to material charge oscillations, have enabled applications in concentrating, guiding and harvesting optical energy below the diffraction limit. Surface plasmon polaritons involve oscillations of electrons and are accessible in noble metals at visible and near-infrared wavelengths, whereas surface phonon polaritons (SPhPs) rely on phonon resonances in polar materials, and are active in the mid-infrared. Noble metal surface plasmon polaritons have limited applications in the mid-infrared. SPhPs at flat interfaces normally possess long polariton wavelengths and provide modest field confinement/enhancement. Here we demonstrate propagating SPhPs in a one-dimensional material consisting of a boron nitride nanotube at mid-infrared wavelengths. The observed SPhP exhibits high field confinement and enhancement, and a very high effective index (neff~70). We show that the modal and propagation length characteristics of the SPhPs may be controlled through the nanotube size and the supporting substrates, enabling mid-infrared applications.


Altered Media Flow and Tablet Position as Factors of How Air Bubbles Affect Dissolution of Disintegrating and Non-disintegrating Tablets Using a USP 4 Flow-Through Cell Apparatus.
This study investigated how air bubbles in media affect tablet dissolution in a flow-through cell system (USP 4) using disintegrating (USP prednisone) and non-disintegrating (USP salicylic acid) tablets. Cell hydrodynamics were studied using particle image velocimetry (PIV) and computational fluid dynamics (CFD). The PIV analysis showed periodic changes in the local flow corresponding to the discharge and suction of the pump cycles. The absence of prior deaeration induced small air bubbles in the media and lower maximum flow during the cycle, explaining the slower dissolution of the USP salicylic acid tablets. Bubbles, occurring during the USP prednisone tablets study, induced the transition of floating disintegrated particles towards the cell outlet, whereas the particles precipitated to form a white layer on the glass beads used in the study with prior deaeration. CFD analysis showed local flow variation in multiple positions of small (ID 12 mm) and large (ID 22.6 mm) cells, explaining the different rates of dissolution of prednisone tablet particles depending on their distribution. These results emphasize the importance of prior deaeration in dissolution studies using a flow-through system. Bubbles in the flow-through cell system affected tablet dissolution by reducing the area in contact with the media (wettability), lowering the maximum instantaneous flow (pressure buffering), and altering the position of disintegrated particles in the cell.


Retroelement-Linked H3K4me1 Histone Tags Uncover Regulatory Evolution Trends of Gene Enhancers and Feature Quickly Evolving Molecular Processes in Human Physiology.
Retroelements (REs) are mobile genetic elements comprising ~40% of human DNA. They can reshape expression patterns of nearby genes by providing various regulatory sequences. The proportion of regulatory sequences held by REs can serve a measure of regulatory evolution rate of the respective genes and molecular pathways. We calculated RE-linked enrichment scores for individual genes and molecular pathways based on ENCODE project epigenome data for enhancer-specific histone modification H3K4me1 in five human cell lines. We identified consensus groups of molecular processes that are enriched and deficient in RE-linked H3K4me1 regulation. We calculated H3K4me1 RE-linked enrichment scores for 24,070 human genes and 3095 molecular pathways. We ranked genes and pathways and identified those statistically significantly enriched and deficient in H3K4me1 RE-linked regulation. Non-coding RNA genes were statistically significantly enriched by RE-linked H3K4me1 regulatory modules, thus suggesting their high regulatory evolution rate. The processes of gene silencing by small RNAs, DNA metabolism/chromatin structure, sensory perception/neurotransmission and lipids metabolism showed signs of the fastest regulatory evolution, while the slowest processes were connected with immunity, protein ubiquitination/degradation, cell adhesion, migration and interaction, metals metabolism/ion transport, cell death, intracellular signaling pathways.


Deoxyribonucleic acid-dependent ribonucleic acid polymerase activity in rat liver after protein restriction.
Rats were fed for 6 days on a diet containing either 3 or 20% high-quality protein. Nuclei were isolated from liver and DNA-dependent RNA polymerases (EC 188.8.131.52) extracted with 1 M-(NH4)2SO4. The proteins were then precipitated with 3.5 M-(NH4)2SO4 and after dialysis applied to a DEAE-Sephadex column. The column was developed with a gradient of (NH4)2SO4. Polymerase I separated well from alpha-amanitin-sensitive polymerase II. The enzyme activities were compared between the two dietary groups. Rats that had received 3% protein showed a lower polymerase I activity per g wet wt. of liver, per mg of DNA and per mg of protein. Polymerase II was lower in activity per g wet wt. of liver and per mg of DNA, but was higher per mg of protein. Polyacrylamide-gel electrophoretograms showed a higher proportion of contaminating proteins in polymerase II fractions isolated from 20%-protein-fed rats. The data explain the lower activity obtained per mg of protein in these rats. It is concluded that a decrease in dietary protein content from 20 to 3% induces a fall in content and specific activity of RNA polymerase I and II in liver.


Neonatal and Pediatric Candidemia: Results From Population-Based Active Laboratory Surveillance in Four US Locations, 2009-2015.
Candida is a leading cause of healthcare-associated bloodstream infections in the United States. Infants and children have unique risk factors for candidemia, and the Candida species distribution in this group is different that among adults; however, candidemia epidemiology in this population has not been described recently. We conducted active population-based candidemia surveillance in 4 US metropolitan areas between 2009 and 2015. We calculated incidences among neonates (0-30 days old), infants (0-364 days old), and noninfant children (1-19 years old), documented their clinical features and antifungal drug resistance. We identified 307 pediatric candidemia cases. Incidence trends varied according to site, but overall, the incidence in neonates decreased from 31.5 cases/100000 births in 2009 to 10.7 to 11.8 cases/100000 births between 2012 and 2015, the incidence in infants decreased from 52.1 cases/100000 in 2009 to 15.7 to 17.5 between 2012 and 2015, and the incidence in noninfant children decreased steadily from 1.8 cases/100000 in 2009 to 0.8 in 2014. Common underlying conditions were prematurity in neonates (78%), surgery in nonneonate infants (38%), and malignancy in noninfant children (28%). Most neonate cases were caused by C albicans (67%), whereas non-C. albicans species accounted for 60% of cases in nonneonate infants and noninfant children. Fluconazole and echinocandin resistance rates were low overall. Thirty-day crude mortality was 13%. The incidence of candidemia among neonates and infants declined after 2009 but remained stable from 2012 to 2015. Antifungal drug resistance is uncommon. Reasons for the lack of recent declines in neonatal and infant candidemia deserve further exploration. In this article, we describe the epidemiology of candidemia in children in the United States and on the basis of data collected as part of US Centers for Disease Control and Prevention active population-based surveillance. Trends in incidence, clinical characteristics, species distribution, and resistance rates are presented.


Mutation analysis of the FRAS1 gene demonstrates new mutations in a propositus with Fraser syndrome.
Fraser syndrome (OMIM 219000) is a rare, autosomal recessive condition with classical features of cryptophthalmos, syndactyly, ambiguous genitalia, laryngeal, and genitourinary malformations, oral clefting and mental retardation. Mutations causing loss of function of the FRAS1 gene have been demonstrated in five patients with Fraser syndrome. However, no phenotype-genotype correlation was established and there was evidence for genetic heterogeneity. Fraser syndrome is rare and the FRAS1 gene has 75 exons, complicating mutation screening in affected patients. We have screened two patients who fulfilled the diagnostic criteria for Fraser syndrome and three patients with related phenotypes (two patients with Manitoba oculotrichoanal syndrome and one patient with unilateral cryptophthalmos and labial fusion) for mutations in FRAS1 to increase the molecular genetic data in patients with Fraser syndrome and related conditions. We report two new mutations in a patient with Fraser syndrome, a frameshift mutation and a deletion of two amino acids that we consider pathogenic as both alter the NG2-like domain of the protein. Although we are still unable to clarify a phenotype-genotype relationship in Fraser syndrome, our data add to the list of mutations associated with this syndrome.


[Revision knee arthroplasty due to aseptic loosening].
Anatomic changes associated with aseptic loosening make conditions for revision of total knee arthroplasty more diffi-cult. The aim of this study was to evaluate the results of revision total knee replacement at an average follow-up of 6.1 years. A total of 97 revision knee replacements due to aseptic loosening carried out in the years 1992 to 2003 were evalua-ted. The group included 46 men and 51 women at an average age of 66.8 years. The average preoperative Knee Society Score (KKS) was 31 points and the Functional Score (FS) was 22 points. There were 41 minor operations for AORI type I defects, 49 moderately serious procedures for AORI type II defects and seven major operations for AORI type III defects. In minor procedures standard components were implanted in 14 patients, standard components with cemented stems with extension were used in nine, and polyethylene plateau exchange was carried out in 18 patients. For moderately serious procedures, posterior stabilized components with extended cemented stems were used in 15 patients, revision implants with cementless stems in 26 patients and standard components with cemented stems in eight patients. In seven patients with major surgery, the hinged type of prosthesis was employed. Radiographic results were evaluated on the basis of Ewald's classification. Clinical findings showed improvement of the average KKS from 31 to 74 points at follow-up of 6.1 years. Functional out-comes improved, as shown by the average FS, from 22 to 67 points. Fifteen patients were not satisfied with the outcome of surgery, the causes being aseptic loosening in four, deep infection in eight and pain due to progression of radiolucent lines of the tibia in three patients. The results of revision surgery with component replacement because of aseptic loosening are worse in comparison with those of primary total knee replacement. The average KSS score after revision surgery was 74 points at 6.1-year follow--up, whereas after primary surgery it was 92 points at 6.5 years. The average FS score after revision was 67 points, as compared with 86 points at 6.5 years after primary surgery. Complications involving infection occurred in 8.2 % of the revi-sion cases, but only in 0.8 % of the primary operations. The authors used modular systems because these provide more options. Good outcomes were achieved with morselized bone grafting for filling cavitary defects. In patients with large defects in tibial or femoral metaphyses, posterior stabilized components and cementless intramedullary stems were used with good results. The authors recommend to avoid filling large bone defects with bone cement. They prefer bone grafting. In the case of good quality metaphyseal bone, they use standard components or posterior stabilized components with or without additi-onal cemented or cementless short stem extensions. In the case of poor quality metaphyseal bone with defects, they use revision implants with cementless long stems. The authors have achieved good results with off-set stems.


Facial vein of the rabbit. Intracellularly recorded hyperpolarization of smooth muscle cells induced by beta-adrenergic receptor stimulation.
A segment of the facial vein of the rabbit gains myogenic tone when placed under tension in a tissue bath (Winquist and Bevan, 1977); low frequency electrical stimulation of intramural nerves, or application of norepinephrine or isoproterenol produces relaxation, which is blocked by propranolol (1.0 microM). We measured membrane potential of single smooth muscle cells with microelectrodes during this beta-adrenergic receptor-mediated relaxation of the vein segment. Hyperpolarization (up to 30 mV) invariably accompanied relaxation. Average maximum resting potential recorded in normal Krebs solution was -46.8 +/- 3.6 mV (mean +/- SE); this increased to -70.8 +/- 3.0 mV when high concentrations (greater than 10 nM) of isoproterenol were added to the bath. Tone and membrane potential were very sensitive to intramural nerve stimulation. At 3-4 Hz, relaxation was about half maximal and hyperpolarization was 6-9 mV. The maximum hyperpolarization to nerve stimulation was 20-30 mV, about the same magnitude as that produced by isoproterenol. Hyperpolarization clearly preceded relaxation by about 0.2 second. The magnitude of hyperpolarization in facial vein is much larger (2-10 times or more) than that recorded in other tissues during inhibition produced by stimulation of beta-adrenergic receptors. The large hyperpolarization may augment the effectiveness of inhibition (by curtailing potential dependent influx of Ca++o, for example) in this tissue compared to that in other tissues in which hyperpolarization is slight or absent. The ionic mechanism underlying hyperpolarization resulting from stimulation of beta-adrenergic receptors remains unclear.


Exercise induces isoform-specific increase in 5'AMP-activated protein kinase activity in human skeletal muscle.
The 5'AMP-activated protein kinase (AMPK) is stimulated by contractile activity in rat skeletal muscle. AMPK has emerged as an important signaling intermediary in the regulation of cell metabolism being linked to exercise-induced changes in muscle glucose and fatty acid metabolism. In the present study, we determined the effects of exercise on isoform-specific AMPK activity (alpha1 and alpha2) in human skeletal muscle. Needle biopsies of vastus lateralis muscle were obtained from seven healthy subjects at rest, after 20 and 60 min of cycle ergometer exercise at 70% of VO(2)max, and 30 min following the 60 min exercise bout. In comparison to the resting state, AMPK alpha2 activity significantly increased at 20 and 60 min of exercise, and remained at a higher level with 30 min of recovery. AMPK alpha1 activity tended to slightly decrease with 20 min of exercise at 70%VO(2)max; however, the change was not statistically significant. AMPK alpha1 activities were at basal levels at 60 min of exercise and 30 min of recovery. On a separate day, the same subjects exercised for 20 min at 50% of VO(2)max. Exercise at this intensity did not change alpha2 activity, and similar to exercise at 70% of VO(2)max, there was no significant change in alpha1 activity. In conclusion, exercise at a higher intensity for only 20 min leads to increases in AMPK alpha2 activity but not alpha1 activity. These results suggest that the alpha2-containing AMPK complex, rather than alpha1, may be involved in the metabolic responses to exercise in human skeletal muscle.


Synthesis of NAC capped near infrared-emitting CdTeS alloyed quantum dots and application for in vivo early tumor imaging.
The synthesis of water-soluble near-infrared (NIR)-emitting quantum dots (QDs) has recently received extensive attention for non-invasive detection of biological information in living subjects. Highly fluorescent CdTeS alloyed QDs for biological application are introduced in this paper. QDs were synthesized by a hydrothermal method and coated with N-acetyl-l-cysteine (NAC) as both bioactive ligand and sulfur source for biocompatibility and biological stability. The optical properties, morphology and structure of CdTeS alloyed QDs were characterized. The in vitro and in vivo toxicity was intensively investigated. Furthermore, the dynamics and bio-distribution of CdTeS alloyed QDs on living mice were studied. To explore biomedical application, folate-polyethylene glycol (FA-PEG) was used to decorate the CdTeS alloyed QDs (FP-CdTeS QDs) for targeted imaging of tumors over-expressing the folate receptor (FR). The tumor targeting capability of FP-CdTeS QDs on tumor bearing nude mice was demonstrated. The results showed that the prepared CdTeS QDs have excellent optical properties and low toxicity, which makes them an ideal inorganic material for biomedical imaging. In addition, the folate-PEG conjugated NIR-QDs displayed good biocompatibility as well as excellent sensitivity and specificity for optical imaging of tumors which can extend the application of CdTeS QDs.


In vitro and in vivo investigations for the development of cytostatic methylhydrazones.
In in vitro short-term (3 h) assays, the beta-chloroethyl-methyl-hydrazones B 1 and B 2 inhibit the uptake of 3H-thymidine by EAC and L 1210 leukemia cells, B 2 being 5 to 10 times more effective than B 1. The growth inhibitory effect of both compounds was also confirmed in long-term (7 days) clonal assays using agar-containing glass capillaries, B 2 again being more effective than B 1. In contrast to these differences in vitro, in vivo both substances showed remission to the same degree in EAC- and complete resistance in L 1210-bearing mice. The diverging in vitro/in vivo sensitivities were thought to result from differences in the affinity of the methylhydrazones to the tumor cells: using short exposure periods (3 h) B 1 was more inhibitory than B 2 on both EAC and L 1210 colony growth; i.e., the more hydrophilic B 2 could more easily be washed off. To further test the idea of different cell membrane affinities, the methylhydrazones ZB 1 and P 1 with increasing lipophilic properties were synthesized. In vitro, after both pulse and continuous exposure ZB 1 and P 1 showed enforced inhibitory effects on colony growth. In vivo, ZB 1 and P 1 reduced the tumor weight of EAC mice, while only P 1 increased the survival time of L 1210 mice. The results suggest that from the combination of in vitro/in vivo assays mechanistic conclusions can be derived that are valuable for further development of these cystostatics.


Circulating Growth Differentiation Factors 11 and 8, Their Antagonists Follistatin and Follistatin-like-3, and Risk of Heart Failure in Elders.
Heterochronic parabiosis has identified growth differentiation factor (GDF)-11 as a potential means of cardiac rejuvenation, but findings have been inconsistent. A major barrier has been lack of assay specificity for GDF-11 and its homolog GDF-8. We tested the hypothesis that GDF-11 and GDF-8, and their major antagonists follistatin and follistatin-like (FSTL)-3, are associated with incident heart failure (HF) and its subtypes in elders. Based on validation experiments, we used liquid chromatography tandem mass spectrometry to measure total serum GDF-11 and GDF-8, along with follistatin and follistatin-like (FSTL)-3 by immunoassay, in two longitudinal cohorts of older adults. In 2,599 participants (age 75.2±4.3) followed for 10.8±5.6 years, 721 HF events occurred. After adjustment, neither GDF-11 (HR per doubling: 0.93 [0.67, 1.30]) nor GDF-8 (HR: 1.02 per doubling [0.83, 1.27]) was associated with incident HF or its subtypes. Positive associations with HF were detected for follistatin (HR: 1.15 [1.00, 1.32]) and FLST-3 (HR: 1.38 [1.03, 1.85]), and with HF with preserved ejection fraction for FSTL-3 (HR: 1.77 [1.03, 3.02]). (All HRs per doubling of biomarker.) FSTL-3 associations with HF appeared stronger at higher follistatin levels and vice versa, and also for men, Blacks and lower kidney function. Among older adults, serum follistatin and FSTL-3, but not GDF-11 or GDF-8, were associated with incident HF. These findings do not support the concept that low serum levels of total GDF-11 or GDF-8 contribute to HF late in life, but do implicate transforming growth factor-βsuperfamily pathways as potential therapeutic targets.


First-night-effect on polysomnographic respiratory sleep parameters in patients with sleep-disordered breathing and upper airway pathology.
The objective of this study is to test whether there is a difference between the polysomnographic (PSG) values of Apnea-hypopnea index (AHI), minimal oxygen saturation (SpO(2)), oxygen desaturation index (ODI) and arousal index recorded on two consecutive nights (so-called "first night effect") in patients with sleep-disordered breathing (SDB) and concomitant upper airway pathology. Retrospective case-control study of polysomnographical recordings of 130 patients (112 males, 18 females, age range 23-80 years) with SDB and upper airway pathology who were tested on two consecutive nights in a hospital sleep laboratory was conducted. Only patients with upper airway pathology without other medical conditions causing SDB were included. AHI, minimal SpO(2), ODI and arousal index values of the first night were compared to those of the second night using Wilcoxon's test. There were no significant statistical differences between AHI, SpO(2), ODI and arousal index values (P = 0.130, P = 0.640, P = 0.052, and P = 0.692, respectively) between the two nights. However, 15% of the patients showed significant variability in the AHI between the two recordings and in 6% of the patients, a diagnosis of severe OSA (AHI > 10/h) would have been missed if only one night of sleep study had been performed. In general, one night of sleep study is sufficient to lead to a clear diagnosis of severe OSA in patients with sleep-disordered breathing and upper airway pathology but may still not diagnose 6% of the patients with severe OSA. Additionally, 15% of the patients showed a significant variability in the AHI between the two nights.


Elevated levels of alpha-2-Heremans-Schmid glycoprotein in CSF of patients with low-grade gliomas.
Little is known about the expression of mitogens and other tumour-related substances in the cerebrospinal fluid (CSF) of glioma patients. The aim of the current study was to determine the presence of aberrant proteins in the CSF of patients with low-grade gliomas. Lumbar puncture was performed in 8 adult patients with supratentorial low-grade gliomas at the time of diagnosis and in 7 controls. Two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionisation time of flight mass spectrometry were used to detect and quantify deviant proteins in the CSF. Two isoforms of alpha(2)-Heremans-Schmid glycoprotein (AHSG) were identified and demonstrated in higher levels in patients with low-grade gliomas compared with the control group consisting of patients with mixed neurological diagnoses (p = 0.001 and p = 0.04, respectively). In 1 patient, the level of AHSG was significantly reduced after gross total resection of the tumour. AHSG appears in the present proteome screening as a novel substance in glioma research. This glycoprotein is expressed in the fetal human brain and is believed to be involved in the embryonic development of the neocortex. Further analyses are planned to determine the significance of the increased levels of AHSG in the CSF of patients with low-grade gliomas.


Coherence in metal-metal-to-ligand-charge-transfer excited states of a dimetallic complex investigated by ultrafast transient absorption anisotropy.
Coherence in the metal-metal-to-ligand-charge transfer (MMLCT) excited state of diplatinum molecule [Pt(ppy)(μ-(t)Bu(2)pz)](2) has been investigated through the observed oscillatory features and their corresponding frequencies as well as polarization dependence in the single-wavelength transient absorption (TA) anisotropy signals. Anticorrelated parallel and perpendicular TA signals with respect to the excitation polarization direction were captured, while minimal oscillatory features were observed in the magic angle TA signal. The combined analysis of the experimental results coupled with those previous calculated in the literature maps out a plausible excited state trajectory on the potential energy surface, suggesting that (1) the two energetically close MMLCT excited states due to the symmetry of the molecule may be electronically and coherently coupled with the charge density shifting back and forth between the two phenylpyridine (ppy) ligands, (2) the electronic coupling strength in the (1)MMLCT and (3)MMLCT states may be extracted from the oscillation frequencies of the TA signals to be 160 and 55 cm(-1), respectively, (3) a stepwise intersystem crossing cascades follows (1)MMLCT → (3)MMLCT (T(1b)) → (3)MMLCT (T(1a)), and (4) a possible electronic coherence can be modulated via the Pt-Pt σ-interactions over a picosecond and survive the first step of intersystem crossing. Future experiments are in progress to further investigate the origin of the oscillatory features. These experimental observations may have general implications in design of multimetal center complexes for photoactivated reactions where coherence in the excited states may facilitate directional charge or energy transfer along a certain direction between different parts of a molecule.


Framework for patient-ventilator asynchrony during long-term non-invasive ventilation.
Episodes of patient-ventilator asynchrony (PVA) occur during acute and chronic non-invasive positive pressure ventilation (NIV). In long-term NIV, description and quantification of PVA is not standardised, thus limiting assessment of its clinical impact. The present report provides a framework for a systematic analysis of polygraphic recordings of patients under NIV for the detection and classification of PVA validated by bench testing. The algorithm described uses two different time windows: rate asynchrony and intracycle asynchrony. This approach should facilitate further studies on prevalence and clinical impact of PVA in long-term NIV.


[Dynamics of hypothalamic CRH immune reactivity in active and passive rats in the course of development of behavioural depression].
A possible relation between activity of the main CRH-producing centers of hypothalamus and depressive-like behavior of animals was studied. We used genetically selected strains--KHA (Koltushi High Avoidance) and KLA (Koltushi Low Avoidance) rats, demonstrating active and passive strategy of adaptive behavior in novelty situaltions, respectively. Rats were exposed to inescapable stress to develop a "learned helplessness". We observed considerable differences between two strains of animals in CRH-expression in parvo-, magno-cellular parts of the paraventricular nucleus and in the supraoptic nucleus in the course of behavioral depression development. Significant differences between control groups were seen only in paraventricular nucleus. On the 1st post-stress day in hypothalamus of KLA rats, we detected decreased CRH immune reactivity that remained unchanged up to the 10th day. In KHA rats, there were no notable changes of CRH expression in all studied nuclei. These findings, including previous results on different dynamics of behavioral changes and different hypothalamo-pituitary-adrenocortical system activity during development of depression in KLA and KHA rats, indicate that "learned helplessness" in these two groups of animals provides the model analogues of different types of depression. Besides, these findings indicate different implication of hypothalamus CRH-system in the behavioral depression development in rats with divergent strategy of adaptive behavior.


Early attainment of breastfeeding competence in very preterm infants.
To explore the development of breastfeeding capacity in very preterm infants, as an immature sucking behaviour is often mentioned as a barrier in the establishment of breastfeeding in these infants. A prospective descriptive design study in which mothers of 15 infants, born at gestational ages between 26 and 31 weeks, used the Preterm Infant Breastfeeding Behaviour Scale for daily assessments of their infants' oral motor behaviour in hospital. Semi-demand feeding with prescription of a total daily volume of milk was practiced during the transition from scheduled to demand feeding. Breastfeeding was initiated from a postmenstrual age (PMA) of 29 weeks. Obvious rooting, efficient areolar grasp, and repeated short sucking bursts were noted from 29 weeks, and occasional long sucking bursts and repeated swallowing from 31 weeks. The maximum number of consecutive sucks was limited to between 5 and 24 sucks, with a median of 17. Full breastfeeding was attained at a median of 35 weeks, between 32 and 38 weeks. The infants' weight gain when fully breastfed was adequate. Very preterm infants have the capacity for early development of oral motor competence that it sufficient for establishment of full breastfeeding at a low postmenstrual age.


An exceptionally bright flare from SGR 1806-20 and the origins of short-duration gamma-ray bursts.
Soft-gamma-ray repeaters (SGRs) are galactic X-ray stars that emit numerous short-duration (about 0.1 s) bursts of hard X-rays during sporadic active periods. They are thought to be magnetars: strongly magnetized neutron stars with emissions powered by the dissipation of magnetic energy. Here we report the detection of a long (380 s) giant flare from SGR 1806-20, which was much more luminous than any previous transient event observed in our Galaxy. (In the first 0.2 s, the flare released as much energy as the Sun radiates in a quarter of a million years.) Its power can be explained by a catastrophic instability involving global crust failure and magnetic reconnection on a magnetar, with possible large-scale untwisting of magnetic field lines outside the star. From a great distance this event would appear to be a short-duration, hard-spectrum cosmic gamma-ray burst. At least a significant fraction of the mysterious short-duration gamma-ray bursts may therefore come from extragalactic magnetars.


The 47-kDa protein involved in the NADPH:O2 oxidoreductase activity of human neutrophils is phosphorylated by cyclic AMP-dependent protein kinase without induction of a respiratory burst.
When human neutrophilic granulocytes are stimulated with chemoattractants or phorbol esters, these cells respond with a so-called respiratory burst: such stimuli induce the activation of a NADPH:O2 oxidoreductase, which converts oxygen into superoxide. This activation coincides with the phosphorylation of a number of proteins, amongst which a 47-kDa phosphoprotein. Neutrophils from patients with the autosomal form of chronic granulomatous disease (CGD) fail to mount a respiratory burst and concomitantly lack phosphorylation of the 47-kDa protein. We have shown this protein to be a substrate for protein kinase C. In the present paper we describe the phosphorylation of the 47-kDa phosphoprotein by cyclic AMP-dependent protein kinase. For these studies, we used neutrophil cytoplasts, i.e., neutrophils devoid of nucleus and granules, but with an intact NADPH:O2 oxidoreductase. Addition of dibutyryl cyclic AMP (Bt2cAMP) to intact human neutrophil cytoplasts resulted in an increase in protein phosphorylation. Among the phosphorylated proteins is a 47-kDa phosphoprotein. Increased protein phosphorylation was also observed upon addition of Bt2cAMP to neutrophil cytoplast lysates. In lysates of neutrophil cytoplasts from patients with the autosomal form of CGD, phosphorylation of the 47-kDa protein was absent. This finding (confirmed by analysis on two-dimensional gels) indicates that the 47-kDa phosphoprotein, relevant for the NADPH:O2 oxidoreductase, is a substrate for the cAMP-dependent protein kinase. Unlike phorbol ester-induced phosphorylation, Bt2cAMP-induced phosphorylation is not accompanied by initiation of a respiratory burst. This observation demonstrates that 47-kDa phosphoprotein phosphorylation can be uncoupled from respiratory burst activity and indicates that other modifications of the NADPH:O2 oxidoreductase are required for induction of activity.


[Haemodynamics during kidney transplantation and general anaesthesia in combination with epidural block and without it in pediatric patients].
To compare haemodynamic effects of general anaesthesia in combination with epidural block and without it during kidney transplantation in Pediatric patients. 61 Pediatric patients undergoing kidney transplantation were divided into two groups. General anaesthesia with sevoflurane, propofol, phentanilum and regional ropivacaine epidural block were used in the group 1. General anaesthesia was used only in the group 2. Haemodynamic parameters were assessed: Arterial blood pressure, stroke volume, central venous pressure and cardiac index. Both techniques of anaesthesia were adequate. regional ropivacaine epidural block and general anaesthesia combination provides more stable haemodynamic parameters than general anaesthesia single use.


Surveillance of tick-borne encephalitis in Europe and case definition.
The study by Stefanoff et al raises two important questions concerning tick-borne encephalitis (TBE) virus infections. First, the lack of a generally accepted case definition and secondly the quality of national surveillance of TBE cases. Ideally, reported cases should be confirmed and the clinically relevant cases with central nervous system (CNS) disease should be separated from febrile cases without CNS manifestations. The surveillance of TBE in the European countries is not uniform and not always mandatory. Efforts to reach a final diagnosis, especially in less severe cases and in children, varies as well as the awareness of the disease in low endemic regions. The only relevant and stable basis for national surveillance is cases with established CNS disease, although immunity to TBE virus after less severe febrile illness is of interest on individual basis. The ratio of non-CNS disease to CNS disease is generally believed to be about three, but there are regional differences in virulence. Significantly, age related differences are basically unknown.


Increased susceptibility to mild neonatal stress in MTHFR deficient mice.
Early life stress is shown to have a life-span outcome on human and animal behavior, increasing the risk for psychopathology. The gene methylenetetrahydrofolate reductase (MTHFR), which encodes for a key enzyme in one carbon metabolism, shows a high prevalence of polymorphism in patients with developmental disorders. Here we examined the hypothesis that MTHFR deficiency results in an increased susceptibility of the developing brain to mild neonatal stress (NS). Mild NS failed to alter corticosterone levels in young and adult Wt mice. However, an elevated level of corticosterone was found in the MTHFR deficient-NS female, exemplifying enhanced sensitivity to NS. Behavioral phenotyping of Wt and MTHFR deficient mice provides evidence that the effect of mild NS may be amplified by the MTHFR deficient genotype. Distinct behavioral characteristics were altered in male and female mice. In general, three patterns of influence on mice behavior were observed: (1) an additive suppressive effect of NS and MTHFR deficiency on exploration and activity was evident in females; (2) stress related parameters were significantly sensitive to genotype in females, presenting an interaction between genotype and sex; (3) various aspects of behavior in a social setting were modified preferably in males by genotype, NS and the interaction between the two, while females exhibited a smaller effect that was restricted to NS with no genotype effect. Overall, our results support an interaction between mild NS, the MTHFR genotype and sex. We suggest using this animal model to study the molecular mechanism linking these two risk factors and their involvement in neurodevelopmental disorders such as schizophrenia and autism.


Beneficial Effect of Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation - Results of the J-RHYTHM Registry 2.
The J-RHYTHM Registry 2 was a multicenter, prospective observational study that extended the follow-up period of the J-RHYTHM Registry in order to investigate long-term outcomes and effects of non-vitamin K antagonist oral anticoagulants (NOACs) in Japanese patients with atrial fibrillation (AF). Among 6,616 patients with nonvalvular AF (NVAF) (men 71.0%, 69.7±9.9 years, CHADS2score 1.7±1.2), event rates were compared among patients receiving warfarin (n=3,964), NOACs (n=923), and no anticoagulation therapy (No-OAC, n=753) at the end of follow-up, except for 976 patients lacking anticoagulant data. During the 5-year follow-up period, thromboembolism occurred in 196 (4.9%), 19 (2.1%), and 45 (6.0%) patients, respectively; major hemorrhage in 233 (5.9%), 22 (2.4%), and 36 (4.8%); all-cause death in 230 (5.8%), 13 (1.4%), and 105 (13.9%), (P<0.001 for each). After adjusting for the components of the CHA2DS2-VASc score and antiplatelet drug use, the odds ratio (OR) in the Warfarin group was significantly lower for all-cause death compared with that in the No-OAC group (OR 0.30, 95% confidence interval [CI] 0.23-0.39, P<0.001), whereas ORs in the NOACs group were significantly lower for all events (OR 0.42, 95% CI 0.24-0.74, P=0.003 for thromboembolism; OR 0.53, 95% CI 0.31-0.93, P=0.027 for major hemorrhage; and OR 0.10, 95% CI 0.06-0.18, P<0.001 for all-cause death, respectively). NOACs could be beneficial for reducing event rates of all types in Japanese NVAF patients.


Chemotherapy, BCG, and serum from tumor-bearing mice: comparative effects on growth and spread of mouse Lewis lung cancer.
In 101 mice, Lewis lung tumor (25 mg apiece) was implanted subcutaneously in the right hind limb and the mice separated into various groups and protocols to test treatment with immunotherapeutic and chemotherapeutic agents. In those treated intralesionally with BCG, the growth of primary tumor was retarded (P smaller than or equal to .05). Tumor growth in animals treated with systemic BCG and serum from tumor-bearing mice was not different from controls. In 14 of 20 mice treated with chemotherapy (semustine and cyclophosphamide), there was no primary or metastatic growth (P smaller than or equal to .01). The observations show that this sort of systemic immunotherapy had no effect on mouse Lewis lung tumor, that intralesionally there was a retarding effect of BCG (although it did not influence metastases), and that this protocol of chemotherapy was strikingly effective.


Accounting for EGFR Mutations in Epidemiologic Analyses of Non-Small Cell Lung Cancers: Examples Based on the International Lung Cancer Consortium Data.
Somatic EGFR mutations define a subset of non-small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches. Through analysis of the International Lung Cancer Consortium (ILCCO) epidemiologic datasets, we developed a regression model for EGFR-status; we then applied a clinical-restriction approach using the optimal cut-point, and a second epidemiologic, multiple imputation approach to ILCCO survival analyses that did and did not account for EGFR-status. Of 35,356 ILCCO patients with NSCLC, EGFR-mutation-status was available in 4,231 patients. A model regressing known EGFR-mutation-status on clinical and demographic variables achieved a concordance index of 0.75 (95% CI, 0.74-0.77) in the training and 0.77 (95% CI, 0.74-0.79) in the testing dataset. At an optimal cut-point of probability-score = 0.335, sensitivity = 69% and specificity = 72.5% for determining EGFR-wildtype status. In both restriction-based and imputation-based regression analyses of the individual roles of BMI on overall survival of patients with NSCLC, similar results were observed between overall and EGFR-mutation-negative cohort analyses of patients of all ancestries. However, our approach identified some differences: EGFR-mutated Asian patients did not incur a survival benefit from being obese, as observed in EGFR-wildtype Asian patients. We introduce a pragmatic method to evaluate the potential impact of EGFR-status on epidemiological analyses of NSCLC. The proposed method is generalizable in the common occurrence in which EGFR-status data are missing.


Does prior benign prostate biopsy predict outcome for patients treated with radical perineal prostatectomy?
To determine the effect of prior benign prostate biopsies on the surgical and clinical outcomes of patients treated with radical perineal prostatectomy for prostate cancer. A total of 1369 patients with clinically localized prostate cancer underwent radical prostatectomy by a single surgeon between 1991 and 2001. A subset of 203 patients (14.9%), who had undergone at least one prior benign prostate biopsy for a rising prostate-specific antigen and/or abnormal digital rectal examination, constituted our study population. A total of 1115 patients with no prior biopsy represented our control group. After prostatectomy, patients were evaluated at 6-month intervals for biochemical evidence of recurrence, defined as a prostate-specific antigen level of 0.5 ng/mL or greater. Patients with a prior benign biopsy had more favorable pathologic features with more organ-confined (74% versus 64%; P <0.001) and less margin-positive (9.8% versus 18%) disease. Only 24 patients (12%) in the study group (versus 20% in control group; P = 0.01) had eventual evidence of biochemical failure. Kaplan-Meier analyses suggested that patients with prior benign biopsies have improved biochemical disease-free survival, especially for those with more aggressive disease (Gleason sum 7 or greater; P <0.01). Overall, patients in the study group had lower probability (odds ratio 0.57, P <0.001) of biochemical failure compared with those in the control group. A prior benign prostate biopsy may be independently associated with more favorable surgical and biochemical outcomes after prostatectomy. Additional studies are needed to confirm these findings.


Nasoseptal flap necrosis: a rare complication of endoscopic endonasal surgery.
OBJECTIVE The vascularized nasoseptal flap (NSF) has become the workhorse for skull base reconstruction during endoscopic endonasal surgery (EES) of the ventral skull base. Although infrequently reported, as with any vascularized flap the NSF may undergo ischemic necrosis and become a nidus for infection. The University of Pittsburgh Medical Center's experience with NSF was reviewed to determine the incidence of necrotic NSF in patients following EES and describe the clinical presentation, imaging characteristics, and risk factors associated with this complication. METHODS The electronic medical records of 1285 consecutive patients who underwent EES at the University of Pittsburgh Medical Center between January 2010 and December 2014 were retrospectively reviewed. From this first group, a list of all patients in whom NSF was used for reconstruction was generated and further refined to determine if the patient returned to the operating room and the cause of this reexploration. Patients were included in the final analysis if they underwent endoscopic reexploration for suspected CSF leak or meningitis. Those patients who returned to the operating room for staged surgery or hematoma were excluded. Two neurosurgeons and a neuroradiologist, who were blinded to each other's results, assessed the MRI characteristics of the included patients. RESULTS In total, 601 patients underwent NSF reconstruction during the study period, and 49 patients met the criteria for inclusion in the final analysis. On endoscopic exploration, 8 patients had a necrotic, nonviable NSF, while 41 patients had a viable NSF with a CSF leak. The group of patients with a necrotic, nonviable NSF was then compared with the group with viable NSF. All 8 patients with a necrotic NSF had clinical and laboratory evidence indicative of meningitis compared with 9 of 41 patients with a viable NSF (p < 0.001). Four patients with necrotic flaps developed epidural empyema compared with 2 of 41 patients in the viable NSF group (p = 0.02). The lack of NSF enhancement on MR (p < 0.001), prior surgery (p = 0.043), and the use of a fat graft (p = 0.004) were associated with necrotic NSF. CONCLUSIONS The signs of meningitis after EES in the absence of a clear CSF leak with the lack of NSF enhancement on MRI should raise the suspicion of necrotic NSF. These patients should undergo prompt exploration and debridement of nonviable tissue with revision of skull base reconstruction.


Measuring Surgical Site Infections in Children: Comparing Clinical, Electronic, and Administrative Data.
Surgical site infections (SSIs) are an important end point and measure of quality of care. Surgical site infections can be identified using clinical registries, electronic surveillance, and administrative claims data. This study compared measurements of SSIs using these 3 different methods and estimated their implication for health care costs. Data were obtained from 5,476 surgical patients treated at a single academic children's hospital (January 1, 2010 through August 31, 2014). Surgical site infections within 30 days were identified using a clinical registry in the NSQIP Pediatric, an electronic surveillance method (Nosocomial Infection Marker; MedMined), and billing claims. Infection rates, diagnostic characteristics, and attributable costs were estimated for each of the 3 measures of SSI. Surgical site infections were observed in 2.24% of patients per NSQIP Pediatric definitions, 0.99% of patients per the Nosocomial Infection Marker, and 2.34% per billing claims definitions. Using NSQIP Pediatric as the clinical reference, Nosocomial Infection Marker had a sensitivity of 31.7% and positive predictive value of 72.2%, and billing claims had a sensitivity of 48.0% and positive predictive value of 46.1% for detection of an SSI. Nosocomial Infection Marker and billing claims overestimated the costs of SSIs by 108% and 41%, respectively. There is poor correlation among SSIs measured using electronic surveillance, administrative claims, and clinically derived measures of SSI in the pediatric surgical population. Although these measures might be more convenient, clinically derived data, such as NSQIP Pediatric, may provide a more appropriate quality metric to estimate the postoperative burden of SSIs in children.


Radiolabeled alpha(v)beta3 integrin antagonists: a new class of tracers for tumor targeting.
The alpha(v)beta3 integrins play an important role during tumor metastasis and tumor-induced angiogenesis. Targeting of this receptor may provide information about the receptor status of the tumor and enable specific therapeutic planning. Cyclo(-Arg-Gly-Asp-D-Phe-Val-) has been shown to be a selective alpha(v)beta3 integrin antagonist with high affinity. In this study we describe the synthesis and biological evaluation of [125I]-3-iodo-D-Tyr4-cyclo(-Arg-Gly-Asp-D-Tyr-Val-) ([125I]P2), [125I]-3-iodo-Tyr5-cyclo(-Arg-Gly-Asp-D-Phe-Tyr-) ([125I]P4) and the negative control peptide [1251]-3-iodo-D-Tyr4-cyclo(-Arg-D-Ala-Asp-Tyr-Val-) ([125I]P6). Peptides were assembled on a solid support using fluorenylmethoxycarbonyl amino acid coupling protocols. Radioiodination was performed using the iodogen method. The in vitro binding assays were performed using isolated, immobilized alphaIIbeta3 and alpha(v)beta3 integrins. Expression of the alphaVbeta3 receptor on the different tumors was validated by immunohistochemical methods using alpha(v) and alpha(v)beta3 specific antibodies. For biodistribution studies, nude mice with melanoma M21 or mammary carcinoma MaCaF and BALB/c mice with osteosarcoma were used. The in vitro binding assays demonstrate that the introduction of tyrosine and subsequent iodination have no influence on the high affinity and selectivity for alpha(v)beta3. Immunohistochemical staining clearly indicates the presence of the alpha(v)beta3 integrins on the tumor tissue of the melanoma and the osteosarcoma. Pretreatment and displacement studies show specific binding of [125I]P2 on melanoma M21-bearing nude mice and osteosarcoma-bearing BALB/c mice but less specific binding on mammary carcinomas. [125I]P2 exhibits fast elimination kinetics. The accumulation in the tumor 10 min postinjection is 2.07 +/- 0.32 %ID/g for the melanoma M21 and 3.50 +/- 0.49 %ID/g for the osteosarcoma and decreases to 1.30 +/- 0.13 %ID/g and 2.03 +/- 0.49 %ID/g 60 min postinjection, respectively. [125I]P4 shows even faster elimination kinetics, resulting in a tumor accumulation of 0.40 +/- 0.10 %ID/g 60 min postinjection for the osteosarcoma-bearing BALB/c mice. Both peptides reveal predominately hepatobiliary excretion. For [1251]P2, this also is confirmed by autoradiography. The negative control peptide [125I]P6 shows no specific activity accumulation. [125I]P2 exhibits high affinity and selectivity for the alpha(v)beta3 integrin in vitro and in vivo and, thus, represents the first radiolabeled alpha(v)beta3 antagonist for the investigation of angiogenesis and metastasis in vivo.


Occurrence of aflatoxins and aflatoxin-producing strains of Aspergillus spp. in soybeans.
Above average rainfall in Maryland during August, September, and October 1971 resulted in heavy mold growth in soybeans while still in the field. Of 28 samples of soybean seed, aflatoxins were found in 14, 2 of which had been used in poultry feed. Aflatoxins were identified by thin-layer chromatography, spectrophotometry, and chicken embryo bioassay. Aspergillus spp. were isolated from 11 samples, and 5 of these isolates produced aflatoxins when grown in liquid culture.


Strength training does not affect the accuracy of force gradation in an isometric force task in young men.
The aim of this study is to investigate potential differences in fine motor control between strength trained (ST) and non-strength trained (NT) individuals. By use of an isometric force production task, two groups, 20 ST (mean age 25.6, SD 4.9) and 19 NT (mean age 24.1, SD 2.9) male individuals, were measured on the ability to control forces with the muscles of their index finger. The maximum voluntary contraction (MVC) was higher in ST than in NT group. Error and SD of the signal increased with increasing force levels in both groups. Despite higher absolute force levels of the ST group, SD and Error were the same in both groups for a given MVC percentage. Signal to noise ratio values showed inverted U-shapes for both groups, with no significant differences between groups on various force levels. The power spectral density analysis disclosed significant differences between groups, with more power in the lowest frequency band (1 - 6 Hz) for the ST group. It is concluded that strength training of arm muscles has no negative effect on the stability of sustained contractions of finger muscles. No evidence was found to support the notion of a loss in accuracy as a result of strength training.


Correlation between the Mechanical Properties and Structural Characteristics of Different Fiber Posts Systems.
The aim of this study was to evaluate the flexural strength and flexural modulus of different fiber-reinforcement composite (FRC) posts and determine the correlation between mechanical properties and structural characteristics. Eleven brands of fiber posts were analyzed (n=10): Exacto Cônico (Angelus), DT Light SL (VDW), RelyX Fiber Post (3M-Espe), Glassix Radiopaque (Nordim), Para Post Fiber White (Coltène), FRC Postec Plus (Ivoclar), Aestheti-Plus Post (Bisco), Superpost Cônico Estriado (Superdont), Superpost Ultrafine (Superdont), Reforpost (Angelus), and White Post DC (FGM). The posts were loaded in three-point bending test to calculate the flexural strength and flexural modulus using a mechanical testing machine (EMIC 2000 DL) at 0.5 mm/min. Data were submitted to one-way ANOVA and Scott-Knot test (p<0.05). The cross-sections of the posts were examined by scanning electron microscopy (SEM). Correlation between the mechanical properties and each of the structural variables was calculated by Pearson's correlation coefficients (p<0.05). The flexural strength values ranged from 493 to 835 MPa and were directly correlated with the fiber/matrix ratio (p=0.011). The flexural modulus ranged from 4500 to 8824 MPa and was inversely correlated with the number of fibers per mm2 of post (p<0.001). It was concluded that the structural characteristics significantly affected the properties of the FRC posts. The structural characteristic and mechanical properties of fiber glass posts are manufacture-dependent. A linear correlation between flexural strength and fiber/matrix ratio, as well as the flexural modulus and the amount of fiber was found.


Clinical Outcomes With Ring Sideroblasts and SF3B1 Mutations in Myelodysplastic Syndromes: MDS Clinical Research Consortium Analysis.
Recurrent somatic mutations in SF3B1 have been identified in patients with myelodysplastic syndromes (MDS) and are associated with ring sideroblasts (RS) and relatively favorable clinical outcomes. The 2016 World Health Organization classification categorizes patients with ≥ 5% RS and SF3B1 mutation as MDS-RS, in contrast to its prior MDS-RS classification (≥ 15% RS, no genotyping data). Treatment responses in MDS patients with mutated SF3B1 are not well described. Patients with MDS and known SF3B1 mutational status were identified from MDS Clinical Research Consortium institutions and grouped when possible as 5% to 15% or ≥ 15% RS. Patients with wild-type versus mutated SF3B1 were matched 2:1 to analyze treatment response. Of 471 patients identified, 16% showed SF3B1 mutation. More patients with mutated SF3B1 were lower-risk MDS. We found that 50% were RS-positive compared to 19% of wild-type patients (P < .001). Having the mutation was associated with better overall survival (hazard ratio = 0.48, P = .001) and longer leukemia-free survival (hazard ratio = 0.5, P < .005). Patients with RS and the mutation had the best outcome. Regarding treatment response, 14 (35%) of 40 erythroid-stimulating agent-treated patients with mutation experienced response versus 9 (16%) of 56 wild-type patients (P = .032), with no differences in response to hypomethylating agents or lenalidomide. SF3B1 mutations in MDS are commonly associated with RS and show better outcomes, with mutated/positive RS presence being significantly better than isolated RS or presence of mutation or neither. Patients with mutation showed better responses to an erythroid-stimulating agent. A new categorization incorporating SF3B1 mutation status, regardless of RS percentage, shows clinical value.


Economic Evaluation of a Telemedicine Service to expand Primary Health Care in Rio Grande do Sul: TeleOftalmo's microcosting analysis.
This study evaluated the cost of public telediagnostic service in ophthalmology. The time-driven activity-based costing method (TDABC) was adopted to examine the cost components related to teleophthalmology. This method allowed us to establish the standard unit cost of telediagnosis, given the installed capacity and utilization of professionals. We considered data from one year of telediagnoses and evaluated the cost per telediagnosis change throughout technology adaptation in the system. The standard cost calculated by distance ophthalmic diagnosis was approximately R$ 119, considering the issuance of 1,080 monthly ophthalmic telediagnostic reports. We identified an imbalance between activities, which suggests the TDABC method's ability to guide management actions and improve resource allocation. The actual unit cost fell from R$ 783 to R$ 283 over one year - with room to approach the estimated standard cost. Partial economic evaluations contribute significantly to support the incorporation of new technologies. The TDABC method deserves prominence, as it enables us to retrieve more accurate information on the cost of technology, improving the scalability and management capacity of the healthcare system.


Improvement of porcine islet isolation by inhibition of trypsin activity during pancreas preservation and digestion using α1-antitrypsin.
Porcine islets are considered to be a promising resource for xenotransplantation. However, it is difficult to isolate porcine islets because of the marked fragility and rapid dissociation. Endogenous trypsin is one of the main factors to damage islets during the isolation procedure. Recent studies have suggested that trypsin inhibitors during the preservation of pancreas or the collagenase digestion can improve the result of islet isolation. In this study, we examined whether α1-antitrypsin (Aralast™), which inhibits several endogenous proteases and has immunomodulatory properties, can protect islets from the proteases and improve the results of porcine islet isolation. Twelve porcine pancreata were divided into three groups: without Aralast group (standard, n = 5), preserved with Aralast using the ductal injection (DI) method (DI, n = 3), and with Aralast using the DI method and in the collagenase solution (DI+C, n = 4). Efficacy of islet isolation was assessed by islet yields, purity, and viability. The trypsin activity of the preservation and the digestion solution during the isolation procedure was measured. During islet isolation, the trypsin activity in DI+C group was significantly inhibited compared to the standard group, whereas DI group showed less effect than DI+C group. The average of postpurification islet equivalents (IEQ) per pancreas weight in the DI+C group was significantly higher than the standard group (standard: 3516 ± 497 IEQ/g, DI: 4607 ± 1090 IEQ/g, DI+C: 7097 ± 995 IEQ/g; p = 0.017 between standard and DI+C). In the DI+C group, stimulation index was higher than in other groups, although there was no significant difference. The presence of Aralast in both DI solution and collagenase solution markedly inhibited trypsin activity during pancreas digestion procedure and improved the porcine islet isolation. Inhibition of trypsin activity by Aralast could improve porcine islet isolation.


Molybdenum disulfide in the poorly crystalline "rag" structure.
Molybdenum disulfide has been prepared in an unusual poorly crystalline form, termed the "rag" structure, consisting of several stacked but highly folded and disordered S-Mo-S layers. This previously unknown structure demonstrates the flexible and macromolecular nature of the layered transition metal dichalcogenides. The determination of this structure provides a basis for understanding its highly broadened x-ray diffraction pattern and relatively low surface area, and is a starting point for optimizing the catalytic and surface properties of molybdenum disulfide.


How do you feel about...? Health outcomes in late life and self-perceptions of health and well-being.
Research has shown over the years that the self-perceptions of older adults about their health and well-being may be at least as important as objective data for predicting the course of their health over time. I review a series of studies that span 30 years in which I and my colleagues have asked older adults in the community about their self-rated health and well-being across a spectrum of parameters, including self-rated health, social support, and mood (both negative and positive), and about whether their basic needs are being met. The social environment shapes perceptions of health and well-being, as does the body. Feelings, such as feelings about health and well-being, are therefore a key (but not the only) psychological-behavioral bridge between the body (genome and physiology) and society (environmental stressors and social context). Following a review of these studies, I attempt to place these perceptions of health and well-being in a social context, a context critical to understanding the consistency and strength of these studies (and others performed over many years) documenting the association between answers to the question "How do you feel about...?" and health outcomes over time.


Systolic and diastolic blood pressures as predictors of coronary heart disease mortality in the Whitehall study.
Systolic and diastolic blood pressures were compared as predictors of death due to coronary heart disease using data on the 10 year mortality outcome from the 18 403 male civil servants, aged 40-64, in the Whitehall study. There were 727 deaths due to coronary heart disease. At entry to the study the systolic pressure in these men was significantly higher than the diastolic pressure, and a standardised index of relative risk for death from coronary heart disease was greater for systolic blood pressure. After adjustment for age the top quintile of systolic pressure (greater than 151 mm Hg) identified 5% more men at risk of death from coronary heart disease than for the top diastolic quintile (greater than 95 mm Hg). The findings suggested that clinicians should pay more attention to systolic levels as a criterion for making diagnostic and therapeutic decisions.