Effect of scheduled second-look endoscopy on peptic ulcer bleeding: a prospective randomized multicenter trial.
This study aimed to investigate the effectiveness of scheduled second-look endoscopy (EGD) with endoscopic hemostasis on peptic ulcer rebleeding and to identify the risk factors related to the need for second-look EGD. We prospectively randomized patients who had endoscopically confirmed bleeding peptic ulcer with stigmata of active bleeding, visible vessel, or adherent clot into 2 groups between August 2010 and January 2013. Hemoclip application or thermal coagulation and/or epinephrine injection were allowed for initial endoscopic therapy. The same dosage of proton pump inhibitor was injected intravenously. The study group received scheduled second-look EGD 24 to 36 hours after the initial hemostasis, and further therapy was applied if endoscopic stigmata persisted, as above. Those patients who developed rebleeding underwent operation or radiologic intervention despite the additional endoscopic therapy. Outcome measures included rebleeding, amount of transfusion, duration of hospitalization, and mortality. After initial endoscopic hemostasis, 319 eligible patients were randomized into 2 groups. Sixteen (10.1%) and 9 (5.6%) patients developed rebleeding (P = .132), respectively. There was also no difference in surgical intervention (0, 0% vs 1, .6%, P >.999) or radiologic intervention (3, 1.9% vs 2, 1.2%, P = .683), median duration of hospitalization (6.0 vs 5.0 days, P = .151), amount of transfusion (2.4 ± 1.7 vs 2.2 ± 1.6 units, P = .276), and mortality (2, 1.3% vs 2, 1.2%, P > .999) between the 2 groups. Multivariate analysis showed that grades 3 to 4 of endoscopists' estimation to success of initial hemostasis, history of nonsteroidal anti-inflammatory drug (NSAID) use, and larger amounts of blood transfusions (≥4 units of red blood cells) were the independent risk factors of rebleeding. A single EGD with endoscopic hemostasis is not inferior to scheduled second-look endoscopy in terms of reduction in rebleeding rate of peptic ulcer bleeding. Repeat endoscopy would be helpful in the patients with unsatisfactory initial endoscopic hemostasis, use of NSAIDs, and larger amounts of transfused blood. (Clinical trial registration number: KCT0000565; 4-2010-0348.).


Reduction of histone proteins dosages increases CFW sensitivity and attenuates virulence of Candida albicans.
Histone proteins are important components of nucleosomes, which play an important role in regulating the accessibility of DNA and the function of genomes. However, the effect of histone proteins dosages on physiological processes is not clear in the human fungal pathogen Candida albicans. In this study, we found that the deletion of the histone protein H3 coding gene HHT21 and the histone protein H4 coding gene HHF1 resulted in a significant decrease in the expression dosage of the histone proteins H3 and H4, which had a significant impact on the localization of the histone protein H2A and plasmid maintenance. Stress sensitivity experiments showed that the mutants hht21Δ/Δ, hhf1Δ/Δ and hht21Δ/Δhhf1Δ/Δ were more sensitive to cell wall stress induced by Calcofluor White (CFW) than the wild-type strain. Further studies showed that the decrease in the dosage of the histone proteins H3 and H4 led to the change of cell wall components, increased chitin contents, and down-regulated expression of the SAP9, KAR2, and CRH11 genes involved in the cell wall integrity (CWI) pathway. Overexpression of SAP9 could rescue the sensitivity of the mutants to CFW. Moreover, the decrease in the histone protein s dosages affected the FAD-catalyzed oxidation of Ero1 protein, resulting in the obstruction of protein folding in the ER, and thus reduced resistance to CFW. It was also found that CFW induced a large amount of ROS accumulation in the mutants, and the addition of ROS scavengers could restore the growth of the mutants under CFW treatment. In addition, the reduction of the histone proteins dosages greatly weakened systemic infection and kidney fungal burden in mice, and hyphal development was significantly impaired in the mutants under macrophage treatment, indicating that the histone proteins dosages is very important for the virulence of C. albicans. This study revealed that histone proteins dosages play a key role in the cell wall stress response and pathogenicity in C. albicans.


A Case of Rare Cutaneous Metastasis from Advanced Pancreatic Cancer.
A 71-year-old woman presented to a nearby hospital with an occipital scalp ulcer with exudate. Thoracoabdominal enhanced computed tomography (CT) was performed due to suspected cancer. The imaging results showed tumors in the pancreatic tail and at multiple sites in the lung, whereupon she was referred to our hospital for further investigation. Histological analysis of the occipital scalp ulcer and the pancreatic tumor led to the diagnosis of pancreatic adenocarcinoma with cutaneous metastasis and multiple lung metastases. Combination chemotherapy (gemcitabine and nab-paclitaxel) was started, and about 4 months later the patient experienced right lower back pain. Abdominal CT showed partial sclerosis of the right iliac bone and multiple spinal lesions, which were diagnosed as multiple bone metastases. Narcotic analgesia was started for the right lower back pain. Since then, FOLFIRINOX has been introduced as second-line chemotherapy against tumor growth, and treatment has been ongoing for 10 months since the initial chemotherapy. Pancreatic cancer is a rapidly growing cancer and can show early metastasis to other organs, lymph node metastasis, and peritoneal dissemination; therefore, the prognosis of pancreatic cancer is very poor. Cutaneous metastasis from pancreatic cancer is rare, and only a few cases have been reported. Here, we report an unusual case of pancreatic adenocarcinoma with cutaneous metastasis and multiple lung and bone metastases.


The introduction of a midwife-led obstetric triage system into a regional referral hospital in Ghana.
to introduce and embed a midwife-led obstetric triage system in a busy labour ward in Accra, Ghana to improve the quality of care and to reduce delay. the study utilized a participatory action research design. Local staff participated in baseline data collection, the triage training course design and delivery, and post-training monitoring and evaluation. a regional referral hospital in Accra, Ghana undertaking 11,032 deliveries in 2012. all midwives and medical staff. measurements included maternal health outcomes, observations of labour ward activity, structured assessments of midwife actions during admission, waiting times, focus group discussions, and learning needs assessments which informed the course content. During training, two quality improvement tools were developed; coloured risk acuity wristbands and a one page triage assessment form. Participants measured compliance and accuracy in the use of these tools following course completion. initially, no formal triage system was in place. The environment was chaotic with poor compliance to existing protocols. Sixty-two midwives received triage training between 2013 and 2014. Two Triage Champions became responsible for triage implementation, monitoring and further training. Following training, the 'in-charge' midwives recorded a cumulative average of 83.4% of women wearing coloured wristbands. A separate audit by the Triage Champions found that 495/535 (93%) of the wristbands were correctly applied based on the diagnosis. Quarterly monitoring of the triage assessment forms by Kybele trainers, showed that 92% recorded the risk acuity colour, 85% a 'working diagnosis' and 82% a 'plan.' Median (interquartile range) waiting times were reduced from 40 (15-100) to 29 (11-60) minutes (p = 007). Twenty of 25 of the staff reported that the wristbands were helpful. an interactive triage training course led to the development of a triage assessment form and the use of coloured patient wristbands which resulted in delay reduction and improved quality of maternity care.


Surgical biatrial ablation of atrial fibrillation: initial results.
To evaluate the results of intraoperative radiofrequency ablation with biatrial procedure in the treatment of chronic atrial fibrillation in patients with associated cardiac disease. Between February 2008 and May 2009, 15 consecutive patients were underwent mitral valve procedure plus modified radiofrequency biatrial ablation of chronic atrial fibrillation. The mean age was 47.73 +/- 9.85 years and 60% were male. The mean left atrial diameter was 55.06 +/- 7.56 mm. There were no hospital mortality or complications related to radiofrequency ablation. The mean follow-up period was 7 +/- 4 months. At the time of hospital discharge nine (60%) patients were in sinus rhythm. After a mean follow-up period 11 (73.3%) were in sinus rhythm. Intraoperative biatrial radiofrequency ablation is a safe and effective technique for the treatment of chronic atrial fibrillation, with satisfactory midterms outcomes in terms of conversion to sinus rhythm.


Multipartite quantum correlations and local recoverability.
Characterizing genuine multipartite quantum correlations in quantum physical systems has historically been a challenging problem in quantum information theory. More recently, however, the total correlation or multipartite information measure has been helpful in accomplishing this goal, especially with the multipartite symmetric quantum (MSQ) discord (Piani et al. 2008 Phys. Rev. Lett. 100, 090502. (doi:10.1103/PhysRevLett.100.090502)) and the conditional entanglement of multipartite information (CEMI) (Yang et al. 2008 Phys. Rev. Lett. 101, 140501. (doi:10.1103/PhysRevLett.101.140501)). Here, we apply a recent and significant improvement of strong subadditivity of quantum entropy (Fawzi & Renner 2014 (http://arxiv.org/abs/1410.0664)) in order to develop these quantities further. In particular, we prove that the MSQ discord is nearly equal to zero if and only if the multipartite state for which it is evaluated is approximately locally recoverable after performing measurements on each of its systems. Furthermore, we prove that the CEMI is a faithful entanglement measure, i.e. it vanishes if and only if the multipartite state for which it is evaluated is a fully separable state. Along the way, we provide an operational interpretation of the MSQ discord in terms of the partial state distribution protocol, which in turn, as a special case, gives an interpretation for the original discord quantity. Finally, we prove an inequality that could potentially improve upon the Fawzi-Renner inequality in the multipartite context, but it remains an open question to determine whether this is so.


Corn trypsin inhibitor coating attenuates the prothrombotic properties of catheters in vitro and in vivo.
Catheters initiate coagulation by activating factor (f) XII, which can lead to catheter thrombosis. Fondaparinux, which only targets activated fX (fXa), is associated with more catheter thrombosis than heparin, which targets fXa and thrombin. To render catheters less thrombogenic and fondaparinux more effective, we examined whether coating catheters with corn trypsin inhibitor (CTI), which blocks fXIIa, attenuates catheter-induced clotting and promotes fondaparinux activity. Compared with unmodified catheters, CTI-coated catheters demonstrated (a) decreased adsorption of fibrinogen and fXII, (b) greater inhibition of fXIIa generated by catheter-induced autoactivation, (c) attenuated fXIIa-mediated activation of fXI and (d) longer plasma clotting times in the absence or presence of fondaparinux. In an accelerated catheter thrombosis model in rabbits, (a) the time to catheter occlusion was longer with CTI-coated catheters than with unmodified catheters and (b) an intravenous dose of fondaparinux that had no effect on the time to occlusion of unmodified catheters extended the time to occlusion of CTI-coated catheters. These findings support the concept that the prothrombotic activity of catheters reflects their capacity to activate fXII and identify CTI immobilization as a novel approach for rendering catheters and other blood-contacting medical devices less thrombogenic.


[Thermography in healthy subjects and in the syndrome of vegetative-vascular dystonia].
The effectiveness and information content of thermography were studied in 20 normal subjects and 40 patients with vegetative vascular dystonia. There were some individuals in the control group who had "thermal amputation" and who also had some specific features of psychovegetative nature. Patients with vegetative vascular dystonia, apart from the syndrome of "thermoamputation" observed in a great number of cases, particularly in neurotic patients, had other types of skin temperature distribution as well. Thus, patients with hypothalamic insufficiency presented with hyperthermia of the distal portions of the extremities and asymmetry.


Fungal host specificity is not a bottleneck for the germination of Pyroleae species (Ericaceae) in a Bavarian forest.
Plants that produce dust seeds can recruit fungi to meet their earliest requirements for carbon and other nutrients. This germination strategy, termed initial mycoheterotrophy, has been well investigated among the orchid family, but there are numerous other plant lineages that have independently evolved mycoheterotrophic germination strategies. One of these lineages is the tribe Pyroleae (Ericaceae). While the fungi associated with mature plants in Pyroleae have been fairly well documented, their mycobionts at the germination and seedling stages are largely unknown. Here, we use an in situ seed baiting experiment along with molecular fingerprinting techniques and phylogenetic tests to identify the fungi associated with seedlings of two Pyroleae species, Pyrola chlorantha and Orthilia secunda. Our results indicate that similar to adult plants, Pyroleae seedlings can associate with a suite of ectomycorrhizal fungi. Some seedlings harboured single mycobionts, while others may have been inhabited by multiple fungi. The dominant seedling mycobiont of both Pyroleae species was a fungus of unknown trophic status in the order Sebacinales. This taxon was also the only one shared among seedlings of both investigated Pyroleae species. We discuss these results juxtaposed to orchids and one additional Pyrola species in the context of ontogenetic shifts in fungal host specificity for mycoheterotrophic nutrition.


The STAR*D study: treating depression in the real world.
The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study evaluated feasible treatment strategies to improve clinical outcomes for real-world patients with treatment-resistant depression. Although the study found no clear-cut "winner", it does provide guidance on how to start therapy and how to proceed if initial treatment fails.


Pegfilgrastim Biosimilars: Where Are We Now?
In 1991, the U.S. Food & Drug Administration (FDA) approved rmetHuGCSF for human use. This recombinant methionyl human granulocyte colony-stimulating factor, or filgrastim, saw use in over 1 million patients in its first 5 years on the market. In 2002, the FDA approved a version of filgrastim with covalent linkage to a monomethoxypolyethylene glycol, increasing the molecular size and half-life to replace multiple days of dosing with a single injection. These medications remained standard of care for neutropenia until the Biologics Price Competition and Innovation Act of 2009 created an abbreviated pathway to licensure for biologic products. Practitioners now have their pick of numerous and expanding options for pegfilgrastim biosimilars.


The conformational changes of alpha 2-macroglobulin induced by methylamine or trypsin. Characterization by extrinsic and intrinsic spectroscopic probes.
The conformational changes around the thioester-bond region of human or bovine alpha 2M (alpha 2-macroglobulin) on reaction with methylamine or trypsin were studied with the probe AEDANS [N-(acetylaminoethyl)-8-naphthylamine-1-sulphonic acid], bound to the liberated thiol groups. The binding affected the fluorescence emission and lifetime of the probe in a manner indicating that the thioester-bond region is partially buried in all forms of the inhibitor. In human alpha 2M these effects were greater for the trypsin-treated than for the methylamine-treated inhibitor, which both have undergone similar, major, conformational changes. This difference may thus be due to a close proximity of the thioester region to the bound proteinase. Reaction of trypsin with thiol-labelled methylamine-treated bovine alpha 2M, which retains a near-native conformation and inhibitory activity, indicated that the major conformational change accompanying the binding of proteinases involves transfer of the thioester-bond region to a more polar environment without increasing the exposure of this region at the surface of the protein. Labelling of the transglutaminase cross-linking site of human alpha 2M with dansylcadaverine [N-(5-aminopentyl)-5-dimethylaminonaphthalene-1-sulphonamide] suggested that this site is in moderately hydrophobic surroundings. Reaction of the labelled inhibitor with methylamine or trypsin produced fluorescence changes consistent with further burial of the cross-linking site. These changes were more pronounced for trypsin-treated than for methylamine-treated alpha 2M, presumably an effect of the cleavage of the adjacent 'bait' region. Solvent perturbation of the u.v. absorption and iodide quenching of the tryptophan fluorescence of human alpha 2M showed that one or two tryptophan residues in each alpha 2M monomer are buried on reaction with methylamine or trypsin, with no discernible change in the exposure of tyrosine residues. Together, these results indicate an extensive conformational change of alpha 2M on reaction with amines or proteinases and are consistent with several aspects of a recently proposed model of alpha 2M structure [Feldman, Gonias & Pizzo (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 5700-5704].


Fresh, stockpiled, and composted beef cattle feedlot manure: nutrient levels and mass balance estimates in Alberta and Manitoba.
The fate of manure nutrients in beef cattle (Bos taurus) feedlots is influenced by handling treatment, yet few data are available in western Canada comparing traditional practices (fresh handling, stockpiling) with newer ones (composting). This study examined the influence of handling treatment (fresh, stockpiled, or composted) on nutrient levels and mass balance estimates of feedlot manure at Lethbridge, Alberta, and Brandon, Manitoba. Total carbon (TC) concentration of compost (161 kg Mg(-1)) was lower (P < 0.001) than stockpiled (248 kg Mg(-1)), which was in turn lower (P < 0.001) than fresh manure (314 kg Mg(-1)). Total nitrogen (TN) concentration was not affected by handling treatment while total phosphorus (TP) concentration increased with composting at Lethbridge. The percent inorganic nitrogen (PIN) was lower (P < 0.01) for compost (5.1%) than both fresh (24.7%) and stockpiled (28.9%) manure. Composting led to higher (P < 0.05) dry matter (DM) losses (39.8%) compared to stockpiling (22.5%) and higher (P < 0.05) total mass (water + DM) losses (65.6 vs. 35.2%). Carbon (C) losses were higher (P < 0.01) with composting (66.9% of initial) than with stockpiling (37.5%), as were nitrogen (N) losses (46.3 vs. 22.5%, P < 0.05). Composting allowed transport of two times as much P as fresh manure and 1.4 times as much P as stockpiled manure (P < 0.001) on an "as is" basis. Our study looked at one aspect of manure management (i.e., handling treatment effects on nutrient concentrations and mass balance estimates) and, as such, should be viewed as one component in the larger context of a life cycle assessment.


Comparison of Cell-based and Nanoparticle-based Therapeutics in Treating Atherosclerosis.
Today, cardiovascular diseases are among the biggest public health threats worldwide. Atherosclerosis, a chronic inflammatory disease with complex aetiology and pathogenesis, predispose many of these conditions, including the high mortality rate-causing ischaemic heart disease and stroke. Nevertheless, despite the alarming prevalence and absolute death rate, established treatments for atherosclerosis are unsatisfactory in terms of efficacy, safety, and patient acceptance. The rapid advancement of technologies in healthcare research has paved new treatment approaches, namely cell-based and nanoparticle-based therapies, to overcome the limitations of conventional therapeutics. This paper examines the different facets of each approach, discusses their principles, strengths, and weaknesses, analyses the main targeted pathways and their contradictions, provides insights on current trends as well and highlights any unique mechanisms taken in recent years to combat the progression of atherosclerosis.


Electron donor-acceptor dyads and triads based on tris(bipyridine)ruthenium(II) and benzoquinone: synthesis, characterization, and photoinduced electron transfer reactions.
Two electron donor-acceptor triads based on a benzoquinone acceptor linked to a light absorbing [Ru(bpy)(3)](2+) complex have been synthesized. In triad 6 (denoted Ru(II)-BQ-Co(III)), a [Co(bpy)(3)](3+) complex, a potential secondary acceptor, was linked to the quinone. In the other triad, 8 (denoted PTZ-Ru(II)-BQ), a phenothiazine donor was linked to the ruthenium moiety. The corresponding dyads Ru(II)-BQ (4) and PTZ-Ru(II) (9) were prepared for comparison. Upon light excitation in the visible band of the ruthenium moiety, electron transfer to the quinone occurred with a rate constant k(f) = 5 x 10(9) s(-)(1) (tau(f) = 200 ps) in all the quinone containing complexes. Recombination to the ground state followed, with a rate constant k(b) approximately 4.5 x 10(8) s(-)(1) (tau(b) approximately 2.2 ns), for both Ru(II)-BQ and Ru(II)-BQ-Co(III) with no indication of a charge shift to generate the reduced Co(II) moiety. In the PTZ-Ru(II)-BQ triad, however, the initial charge separation was followed by a rapid (k > 5 x 10(9) s(-)(1)) electron transfer from the phenothiazine moiety to give the fairly long-lived PTZ(*)(+)-Ru(II)-BQ(*)(-) state (tau = 80 ns) in unusually high yield for a [Ru(bpy)(3)](2+)-based triad (> 90%), that lies at DeltaG degrees = 1.32 eV relative to the ground state. Unfortunately, this triad turned out to be rather photolabile. Interestingly, coupling between the oxidized PTZ(*)(+) and the BQ(*)(-) moieties seemed to occur. This discouraged further extension to incorporate more redox active units. Finally, in the dyad PTZ-Ru(II) a reversible, near isoergonic electron transfer was observed on excitation. Thus, a quasiequilibrium was established with an observed time constant of 7 ns, with ca. 82% of the population in the PTZ-Ru(II) state and 18% in the PTZ(*)(+)-Ru(II)(bpy(*)(-)) state. These states decayed in parallel with an observed lifetime of 90 ns. The initial electron transfer to form the PTZ(*)(+)-Ru(II)(bpy(*)(-)) state was thus faster than what would have been inferred from the Ru(II) emission decay (tau = 90 ns). This result suggests that reports for related PTZ-Ru(II) and PTZ-Ru(II)-acceptor complexes in the literature might need to be reconsidered.


Prevalence and correlates of multimorbidity among adults in Botswana: A cross-sectional study.
Botswana is currently undergoing rapid epidemiological transition indicated by a decline in infectious diseases and an increase in chronic non-communicable diseases and their associated risk factors. The main aim of this study was to assess prevalence and correlates of multimorbidity among the adult population in Botswana. A cross-sectional study called Chronic Non-Communicable Diseases Study (NCDs study) was conducted in March, 2016. Using multistage cross sectional sampling design, 1178 male and female respondents aged 15 years and above were interviewed across 3 cities and towns, 15 urban villages and 15 rural villages. Participants were interviewed face-to-face using a structured questionnaire. Adjusted multinomial logistic regression analysis was used to assess covariates of multimorbidity. The statistical significant level was fixed at p <0 .05. Prevalence of multimorbidity in the sampled population was estimated at 5.4%. Multivariate results indicate that the odds of multimobridty were significantly high among women (AOR = 3.34, 95% C.I. = 1.22-21.3) than men. On the other hand, the odds of multimorbidity were significantly low among young people aged below 24 years (AOR = 0.01, 95% C.I. = 0.00-0.07), currently married people (AOR = 0.24, 95% C.I. = 0.07-0.80) and individuals in the 2nd wealth quintile (AOR = 0.20, 95% C.I. = 0.05-0.75) compared to their counterparts. For behavioural risk factors, alcohol consumption (AOR = 4.80, 95% C.I. = 1.16-19.8) and overweight/obesity (AOR = 1.44, 95% CI = 1.12-2.61) were significantly associated with high multimorbidity prevalence. Multimorbidity was found to be more prevalent among women, alcohol consumers and overweight/obese people. There is need to strengthen interventions encouraging healthy lifestyles such as non-consumption of alcohol, physical activity and healthy diets. Moreover, there is need for a holistic approach of health care services to meet the needs of those suffering from multimorbidity.


Characteristics of animal-related motor vehicle crashes in select National Park Service units-United States, 1990-2013.
Nationally, animal-motor vehicle crashes (AVCs) account for 4.4% of all types of motor vehicle crashes (MVCs). AVCs are a safety risk for drivers and animals and many National Park Service (NPS) units (e.g., national park, national monument, or national parkway) have known AVC risk factors, including rural locations and substantial animal densities. We sought to describe conditions and circumstances involving AVCs to guide traffic and wildlife management for prevention of AVCs in select NPS units. We conducted an analysis using NPS law enforcement MVC data. An MVC is a collision involving an in-transit motor vehicle that occurred or began on a public roadway. An AVC is characterized as a collision between a motor vehicle and an animal. A non-AVC is a crash between a motor vehicle and any object other than an animal or noncollision event (e.g., rollover crash). The final data for analysis included 54,068 records from 51 NPS units during 1990-2013. Counts and proportions were calculated for categorical variables and medians and ranges were calculated for continuous variables. We used Pearson's chi-square to compare circumstances of AVCs and non-AVCs. Data were compiled at the park regional level; NPS parks are assigned to 1 of 7 regions based on the park's location. AVCs accounted for 10.4% (5,643 of 54,068) of all MVCs from 51 NPS units. The Northeast (2,021 of 5,643; 35.8%) and Intermountain (1,180 of 5,643; 20.9%) regions had the largest percentage of the total AVC burden. November was the peak month for AVCs across all regions (881 of 5,643; 15.6%); however, seasonality varied by park geographic regions. The highest counts of AVCs were reported during fall for the National Capital, Northeast/Southeast, and Northeast regions; winter for the Southeast region; and summer for Intermountain and Pacific West regions. AVCs represent a public health and wildlife safety concern for NPS units. AVCs in select NPS units were approximately 2-fold higher than the national percentage for AVCs. The peak season for AVCs varied by NPS region. Knowledge of region-specific seasonality patterns for AVCs can help NPS staff develop mitigation strategies for use primarily during peak AVC months. Improving AVC data collection might provide NPS with a more complete understanding of risk factors and seasonal trends for specific NPS units. By collecting information concerning the animal species hit, park managers can better understand the impacts of AVC to wildlife population health.


Endothelin-1 signaling promotes fibrosis in vitro in a bronchopulmonary dysplasia model by activating the extrinsic coagulation cascade.
Neonatal respiratory distress syndrome can progress to bronchopulmonary dysplasia (BPD), a serious pulmonary fibrotic disorder. Given the involvement of the extrinsic coagulation cascade in animal models of lung fibrosis, we examined its role in BPD. We observed a higher number of neutrophils expressing tissue factor (TF) in bronchoalveolar lavage fluid (BALF) from infants with BPD than from those with uncomplicated respiratory distress syndrome together with a parallel decrease in TF and connective tissue growth factor (CTGF) in BALF supernatants during the disease course. The involvement of coagulation in the fibrotic process associated with BPD was further evaluated by treating primary human colonic myofibroblasts with BALF supernatants from infants with BPD. These human colonic myofibroblasts demonstrated an enhanced C5a- and thrombin-dependent migration. Moreover, they expressed TF in an endothelin-1-dependent manner, with subsequent activation of the extrinsic coagulation cascade and CTGF production mediated by protease-activator receptor-1 signaling. These data provide a novel mechanism for the development of BPD and indicate that endothelin-1 signaling contributes to fibrosis by upregulating a TF/thrombin amplification loop responsible for CTGF production, and offer novel and specific therapeutic targets for pulmonary fibrotic disease.


Meningeal melanocytoma: clinical features and review of the literature.
A case of meningeal melanocytoma in the posterior fossa of a 16-year-old male is reported. Computed tomographic and magnetic resonance imaging features are presented. Pathological investigation including light and electron microscopy, and immunohistochemical staining are discussed. Current literature is reviewed and differentiating criteria from meningioma and other pigmented tumours of the nervous system are discussed.


The relationship between reinforcement and gaming machine choice.
The present study assessed whether prior reinforcement experiences were related to gaming machine choice and the decision to change gaming machines during a session of gambling. Seventy undergraduate students (48 women, 22 men; mean age = 22.05 years) were presented with two visually identical simulated gaming machines in a practice phase. These simulated machines differed only in the rate of reinforcement. After the practice phase, participants were asked to choose a machine to play in the test phase and were allowed to change machines at will. Two measures of reinforcement were employed; frequency of wins and payback rate. Results indicated that neither measure of reinforcement was related to machine choice, but both were predictors of when participants changed machines. A post-hoc analysis of the 33 participants who changed machines during the test phase found a significant relationship between machine choice and prior reinforcement. For these participants, payback rate was significantly related to machine choice, unlike frequency of wins.


Laboratory demonstration of a cryogenic deformable mirror for wavefront correction of space-borne infrared telescopes.
This paper demonstrates a cryogenic deformable mirror (DM) with 1020 actuators based on micro-electrical mechanical systems (MEMS) technology. Cryogenic space-borne infrared telescopes can experience a wavefront error due to a figure error of their mirror surface, which makes the imaging performance worse. For on-orbit wavefront correction as one solution, we developed a MEMS-processed electro-static DM with a special surrounding structure for use under the cryogenic temperature. We conducted a laboratory demonstration of its operation in three cooling cycles between 5 K and 295 K. Using a laser interferometer, we detected the deformation corresponding to the applied voltages under the cryogenic temperature for the first time. The relationship between voltages and displacements was qualitatively expressed by the quadratic function, which is assumed based on the principle of electro-static DMs. We also found that it had a high operating repeatability of a few nm root-mean-square and no significant hysteresis. Using the measured values of repeatability, we simulated the improvement of the point spread function (PSF) by wavefront correction with our DM. These results show that our developed DM is effective in improving imaging performance and PSF contrast of space-borne infrared telescopes.


Identification of membrane-contacting loops of the catalytic domain of cytochrome P450 2C2 by tryptophan fluorescence scanning.
The catalytic domain of cytochrome P450 is thought to contact the lipid core of the endoplasmic reticulum membrane based on antibody epitope accessibility, protease susceptibility, and hydrophobic surfaces present on P450 structures of solubilized forms of the proteins. Quenching by nitroxide spin label-modified phospholipids of the fluorescence of tryptophan residues substituted into cytochrome P450 2C2, modified to contain tryptophan only at position 120, was used to identify regions of P450 inserted into the lipid core and to estimate the depth of penetration. Consistent with the proposed models of cytochrome P450-membrane interaction, the fluorescence of tryptophans inserted at residues 36 and 69 in the two segments of P450 2C2 flanking the A-helix and at residue 380 in the beta2-2 strand was quenched by nitroxide spin labels on carbon 5 of the fatty acid tails of the phospholipids within the lipid bilayer. The fluorescence of tryptophan at 380 was also strongly quenched by a spin label on carbon 12 of the fatty acids suggesting it was deepest in the membrane. However, fluorescence of tryptophan substituted at residue 225 in the F-G loop, which was predicted to be in the lipid bilayer, was not quenched by the spin labels at carbons 5 and 12 of the fatty acids. The pattern of quenching of fluorescence for tryptophans at the other positions tested, 80, 189, 239, and 347, was similar to the parent protein indicating they were not inserted into the lipid bilayer as expected. The results are consistent with an orientation of cytochrome P450 2C2 in the membrane in which positions 36, 69, and 380 are inserted into the lipid bilayer and residues 80 and 225 are near or within the phospholipid headgroup region. In this orientation, the F-G loop, which contains residue 225, could form a dimerization interface as was observed in the P450 2C8 crystal structure (Schoch, G. A., et al. (2004) J. Biol. Chem. 279, 9497).


Crystal-Induced Podocytopathy Producing Collapsing Focal Segmental Glomerulosclerosis in Monoclonal Gammopathy of Renal Significance: A Case Report.
Monoclonal gammopathy-associated crystalline podocytopathy causing collapsing focal segmental glomerulosclerosis (FSGS) is very rare and has been associated with pamidronate therapy. We present the case of a 53-year-old man with vision loss secondary to corneal crystals deposition, nephrotic-range proteinuria, and reduced glomerular filtration rate without associated comorbid conditions. Two kidney biopsies were initially reported as primary FSGS but the patient did not respond to high-dose corticosteroid immunosuppression therapy. Repeat review of biopsies with additional electron microscopy analysis revealed crystalline inclusions in podocytes leading to collapsing FSGS. Subsequent workup revealed an immunoglobulin G κ serum monoclonal protein. Bone marrow biopsy revealed 5% κ-restricted plasma cells with cytoplasmic crystalline inclusions. To our knowledge, this is the first case of monoclonal gammopathy of clinical significance manifesting as crystalline podocytopathy leading to collapsing FSGS and keratopathy leading to vision loss. Crystalline podocytopathy should be considered in the differential diagnosis of collapsing glomerulopathy, and careful ultrastructural examination of the kidney biopsy specimen is crucial to establish this diagnosis.


Imaging to select and guide transcatheter aortic valve implantation.
Transcatheter aortic valve implantation (TAVI) is indicated for patients with severe aortic stenosis and high or prohibitive surgical risk. Patients' selection requires clinical and anatomical selection criteria, being the later determined by multimodality imaging evaluation. Echocardiography, multislice computed tomography (MSCT), angiography, and cardiovascular magnetic resonance (CMR) are the methods available to determine the anatomical suitability for the procedure. Imaging assists in the selection of bioprosthesis type, prosthetic sizing and in the decision of the best vascular access. In this review, we present our critical appraisal on the use of imaging to best patients' selection and procedure guidance in TAVI.


Special Report on the Impact of the COVID-19 Pandemic on Clinical EEG and Research and Consensus Recommendations for the Safe Use of EEG.
The global COVID-19 pandemic has affected the economy, daily life, and mental/physical health. The latter includes the use of electroencephalography (EEG) in clinical practice and research. We report a survey of the impact of COVID-19 on the use of clinical EEG in practice and research in several countries, and the recommendations of an international panel of experts for the safe application of EEG during and after this pandemic. Fifteen clinicians from 8 different countries and 25 researchers from 13 different countries reported the impact of COVID-19 on their EEG activities, the procedures implemented in response to the COVID-19 pandemic, and precautions planned or already implemented during the reopening of EEG activities. Of the 15 clinical centers responding, 11 reported a total stoppage of all EEG activities, while 4 reduced the number of tests per day. In research settings, all 25 laboratories reported a complete stoppage of activity, with 7 laboratories reopening to some extent since initial closure. In both settings, recommended precautions for restarting or continuing EEG recording included strict hygienic rules, social distance, and assessment for infection symptoms among staff and patients/participants. The COVID-19 pandemic interfered with the use of EEG recordings in clinical practice and even more in clinical research. We suggest updated best practices to allow safe EEG recordings in both research and clinical settings. The continued use of EEG is important in those with psychiatric diseases, particularly in times of social alarm such as the COVID-19 pandemic.


Physical activity and sedentary behavior among adolescents in rural South Africa: levels, patterns and correlates.
Physical inactivity is increasing among children and adolescents and may be contributing to the increasing prevalence of overweight and obesity. This study examines physical activity and sedentary behavior patterns, and explores associations with individual, maternal, household, and community factors amongst rural South African adolescents. In 2009, 381 subjects, stratified by ages 11-12-years and 14-15-years, were randomly selected from 3511 children and adolescents who had participated in a growth survey two years previously. Weight and height were measured and self-reported Tanner pubertal stage was collected. A questionnaire quantifying frequency and duration of physical activity (PA) domains and sedentary time for the previous 12 months was administered. Moderate-vigorous physical activity (MVPA mins/wk) was calculated for time spent in school and club sport. Socio-demographic and other related data were included from the Agincourt health and socio-demographic system (HDSS). The Agincourt HDSS was established in 1992 and collects prospective data on the community living in the Agincourt sub-district of Mpumalanga Province in rural north-east South Africa. Puberty, maternal education and socio-economic status (SES) contributed significantly to the mulitiple linear regression model for sedentary behavior (R2 = 0.199; adjusted R2 = 0.139; p < 0.000), and sex, SES and maternal education contributed to the tobit regression model for school and club sport MVPA (p < 0.000). MVPA, calculated from school and club sport, was higher in boys than girls (p < 0.001), and informal activity was lower (boys: p < 0.05 and girls: p < 0.01) while sedentary time was higher (girls: p < 0.01) in the older than the younger groups. Ninety-two percent (92%) of the sample reported walking for transport. In this study of rural South African adolescent boys and girls, SES at the maternal, household and community level independently predicted time spent in sedentary behaviors, and school and club MVPA. This study provides local data that can be used to develop health promotion strategies specific to this community, and other similar communities in developing countries.


An exact method for finding short motifs in sequences, with application to the ribosome binding site problem.
This is an investigation of methods for finding short motifs that only occur in a fraction of the input sequences. Unlike local search techniques that may not reach a global optimum, the method proposed here is guaranteed to produce the motifs with greatest z-scores. This method is illustrated for the Ribosome Binding Site Problem, which is to identify the short mRNA 5' untranslated sequence that is recognized by the ribosome during initiation of protein synthesis. Experiments were performed to solve this problem for each of fourteen sequenced prokaryotes, by applying the method to the full complement of genes from each. One of the interesting results of this experimentation is evidence that the recognized sequence of the thermophilic archaea A. fulgidus, M. jannaschii, M. thermoautotrophicum, and P. horikoshii may be somewhat different than the well known Shine-Dalgarno sequence.


The predominant species of nonstructural protein 4B in hepatitis C virus-replicating cells is not palmitoylated.
Hepatitis C virus (HCV) represents a significant global health burden. Viral replication is thought to occur in close association with remodelled host cell membranes, with non-structural protein 4B (NS4B) being a key player in this process. NS4B is a poorly characterized integral membrane protein, which has been reported to be palmitoylated at its carboxy-terminal end. In order to extend this observation and to establish a functional role for NS4B palmitoylation, we sought to determine the status of this post-translational modification when the protein was expressed as part of a functional viral replicase. We performed direct metabolic labelling and polyethylene glycol-maleimide palmitoylation reporter assays on NS4B expressed in cells containing subgenomic replicons and infectious viral RNA. In a vaccinia virus-based expression system NS4B palmitoylation was detected in a genotype-dependent manner. However, in spite of the high sensitivity of the methods used, no NS4B palmitoylation was found in physiologically more relevant systems. Thus, NS4B palmitoylation is most likely dispensable for HCV RNA replication.


Lost in the map.
Organismal development and evolution are complex, multifaceted processes that depend intimately on context. They are subject to environmental influences, chance appearance and fixation of mutations, and numerous other idiosyncrasies. Genomics is detailing the molecular signature of effects of these mechanisms on phenotypes, but because numerous distinct evolutionary explanations can produce a given genomic pattern, the molecular details, rather than elucidating process, typically distract from explanatory insight and contribute little to predictive capability. While genomic research has burgeoned, direct study of evolutionary and developmental processes has lagged. We advocate for reinvigoration of direct study of process, along with refocusing of attention on questions of broad biological import, as more productive of urgently needed insights, which genomic approaches are not providing.


Long-term patency of on- and off-pump coronary artery bypass grafting with bilateral internal thoracic arteries: the significance of late string sign development in the off-pump technique.
This study aimed to examine the effect of off-pump coronary artery bypass grafting (CABG) in patients who underwent revascularization with bilateral internal thoracic arteries (ITAs). Between January 2000 and December 2014, 499 patients underwent isolated CABG with bilateral ITAs for complete revascularization of the left coronary system at our institution. On-pump CABG was performed in 137 patients, and off-pump CABG was performed in 362 patients. We retrospectively compared the clinical outcomes and patency of the ITAs. The off-pump group showed less respiratory failure and required a shorter postoperative stay than the on-pump group. The survival probability, freedom from cardiac events and early graft patency were similar in both groups. Five-year patency of the ITA anastomosed to the left anterior descending artery was significantly greater in the on-pump group than in the off-pump group (98.8% vs 91.2%, P = 0.010). The incidence of string change in the off-pump group was higher than that in the on-pump group (P = 0.017). There was no significant difference between the groups in the 5-year patency of the ITA anastomosed to the left circumflex artery (on-pump group: 93.8%, off-pump group: 91.8%; P = 0.46). The early graft patency and the late patency of the ITA anastomosed to the left circumflex artery between the groups were similar, implying an equivalent quality of anastomoses. However, the patency of the ITA anastomosed to the left anterior descending artery in the off-pump group showed late deterioration, mainly because of string sign development.


DNA synthesis at the site of a Red-mediated exchange in phage lambda.
In phage lambda, progeny particles bearing unreplicated chromosomes are recombinant by action of lambda's Red system only near the right end of the chromosome. These recombinants are frequently heterozygous (heteroduplex) for markers located there. In replication-blocked crosses involving two heavy-labeled parents we find that particles in the solitary peak, containing progeny with fully conserved DNA, vary in density. Those on the heavy side of this peak are more apt to be heterozygous than are those on the light side. The data fit a model in which a double chain cut at cos, lambda's packaging origin, is followed by partial exonucleolytic degradation of lambda's r chain from the right end leftward. The exposed l chain, which thereby constitutes a 3' overhang, invades an intact, circular homologue after itself suffering some degradation. Completion of the recombinant chromosome sometimes involves DNA synthesis primed by the invading chain.


International Family, Adult, and Child Enhancement Services (FACES): a community-based comprehensive services model for refugee children in resettlement.
The development of evidence-based mental health interventions for refugees is complicated by the cultural and linguistic diversity of the participants, and the need to balance treatment of past traumatic experiences with ongoing support during the process of acculturation. In an effort to gather "practice-based evidence" from existing mental health services for refugees, a collaborative study of International Family, Adult, and Child Enhancement Services (FACES), a comprehensive, community-based mental health program working with refugee children, was conducted to describe the program participants and service delivery model and to assess whether participants improved over time as a function of services. Results showed that participants improved, but that the improvement was not related to dosage of services. Implications of these findings for refugee mental health services are discussed and suggestions are made for future evaluation research of mental health services with refugees.


Temporally stable genetic variability and dynamic kinship structure in a fluctuating population of the root vole Microtus oeconomus.
Genetic variability, kin structure and demography of a population are mutually dependent. Population genetic theory predicts that under demographically stable conditions, neutral genetic variability reaches equilibrium between gene flow and drift. However, density fluctuations and non-random mating, resulting e.g. from kin clustering, may lead to changes in genetic composition over time. Theoretical models also predict that changes in kin structure may affect aggression level and recruitment, leading to density fluctuations. These predictions have been rarely tested in natural populations. The aim of this study was to analyse changes in genetic variability and kin structure in a local population of the root vole (Microtus oeconomus) that underwent a fourfold change in mean density over a 6-year period. Intensive live-trapping resulted in sampling 88% of individuals present in the study area, as estimated from mark-recapture data. Based on 642 individual genotypes at 20 microsatellite loci, we compared genetic variability and kin structure of this population between consecutive years. We found that immigration was negatively correlated with density, while the number of kin groups was positively correlated with density. This is consistent with theoretical predictions that changes in kin structure play an important role in population fluctuations. Despite the changes in density and kin structure, there was no genetic differentiation between years. Population-level genetic diversity measures did not significantly vary in time and remained relatively high (H(E) range: 0.72-0.78). These results show that a population that undergoes significant demographic and social changes may maintain high genetic variability and stable genetic composition.


Contraversive ocular tilt reaction after the lateral medullary infarction.
The triad of ocular tilt reaction (OTR) is conjugated ocular torsion, skewed deviation, and head tilt. A lesion involving below the inferior pons develops ipsiversive OTR, whereas a lesion above the inferior pons leads to contraversive OTR. A lateral medullary infarction usually causes ipsiversive OTR. This is the first report of contraversive OTR following the lateral medullary infarction. A 58-year-old woman was admitted due to sudden-onset vertigo and gait disturbance. A neurological examination revealed OTR to the left side (left head tilt, leftward ocular torsion, and skew deviation). Lateropulsion to the right and dysmetria on the right arm and leg were present. Diffusion-weighted MRI revealed an acute infarction of the right lateral medulla and the posterolateral pons. The patient slowly improved and can walk without sway after 1 week. Neither head tilt nor ataxia was observed after 3 months. Lateral medullary lesion typically results in ipsilateral OTR. Contraversive OTR of our patient might be derived from the disruption of the cerebellovestibular inhibitory pathway by the lesion in the juxtarestiform body in the lateral medulla.


[Management of recurrent soft tissue sarcoma of the retroperitoneum].
Local recurrence is the determinant of tumor-related mortality in retroperitoneal sarcomas because death often occurs as a result of local progression mostly without synchronous metastasis. Complete resection of the lesion and surgical margins status are the only therapeutic factors significantly associated with local control. Further outcome improvements need multimodal therapy since prognosis of these recurrences is poor with lower rates of complete resection and higher grade of malignancy than primary. Complete resection of the recurrence often requires removal of adjacent organs to achieve negative margins. External beam radiotherapy (EBRT), eventually associated with a boost of intra-operative electron beam radiotherapy (IORT) could improve the outcome in these patients. Preoperative timing could limit its toxicity. Chemotherapy protocols may enhance local and systemic outcome and can reduce the volume of high grade tumors and therefore allow a higher rate of complete resection. Isolated pelvic perfusion with local high doses chemotherapy is under investigation. Surgical excision of lung metastases should remain the treatment of choice, if preoperative evaluation indicates that complete clearance of the metastases is possible. Intra-operative chemotherapy after cyto-reductive surgery for the treatment of sarcomatosis is disappointing and complete surgery remains the cornerstone of the treatment with best results for low grade sarcomatosis. Adequate management at the time of primary presentation is likely to afford the best chance for long-term survival.


Ventriculo-arterial coupling detects occult RV dysfunction in chronic thromboembolic pulmonary vascular disease.
Chronic thromboembolic disease (CTED) is suboptimally defined by a mean pulmonary artery pressure (mPAP) <25 mmHg at rest in patients that remain symptomatic from chronic pulmonary artery thrombi. To improve identification of right ventricular (RV) pathology in patients with thromboembolic obstruction, we hypothesized that the RV ventriculo-arterial (Ees/Ea) coupling ratio at maximal stroke work (Ees/Eamax sw) derived from an animal model of pulmonary obstruction may be used to identify occult RV dysfunction (low Ees/Ea) or residual RV energetic reserve (high Ees/Ea). Eighteen open chested pigs had conductance catheter RV pressure-volume (PV)-loops recorded during PA snare to determine Ees/Eamax sw This was then applied to 10 patients with chronic thromboembolic pulmonary hypertension (CTEPH) and ten patients with CTED, also assessed by RV conductance catheter and cardiopulmonary exercise testing. All patients were then restratified by Ees/Ea. The animal model determined an Ees/Eamax sw = 0.68 ± 0.23 threshold, either side of which cardiac output and RV stroke work fell. Two patients with CTED were identified with an Ees/Ea well below 0.68 suggesting occult RV dysfunction whilst three patients with CTEPH demonstrated Ees/Ea ≥ 0.68 suggesting residual RV energetic reserve. Ees/Ea > 0.68 and Ees/Ea < 0.68 subgroups demonstrated constant RV stroke work but lower stroke volume (87.7 ± 22.1 vs. 60.1 ± 16.3 mL respectively, P = 0.006) and higher end-systolic pressure (36.7 ± 11.6 vs. 68.1 ± 16.7 mmHg respectively, P < 0.001). Lower Ees/Ea in CTED also correlated with reduced exercise ventilatory efficiency. Low Ees/Ea aligns with features of RV maladaptation in CTED both at rest and on exercise. Characterization of Ees/Ea in CTED may allow for better identification of occult RV dysfunction.


[Visual acuity and work and leisure abilities].
The visual medical ability is necessary for a large number of jobs, sports and for vehicles driving. A high heterogeneousity exists in the required standards, the measurement techniques and the people who realize these visual abilities. This heterogeneousity is too rarely correlated to an accidentology which is increased by a lack of scientific study. A review non exhaustive of jobs and occupations is here presented.


Animal-assisted interventions as innovative tools for mental health.
There is a growing interest for the potential health benefits of human-animal interactions. Although scientific evidence on the effects is far from being consistent, companion animals are used with a large number of human subjects, ranging from children to elderly people, who benefit most from emotional support. Based on a comprehensive review of the literature, this paper examines the potential for domesticated animals, such as dogs, for providing emotional and physical opportunities to enrich the lives of many frail subjects. In particular, we focus on innovative interventions, including the potential use of dogs to improve the life of emotionally-impaired children, such as those affected by autism spectrum disorders. Overall an ever increasing research effort is needed to search for the mechanism that lie behind the human-animal bond as well as to provide standardized methodologies for a cautious and effective use of animal-assisted interventions.


The role of motivation in distracting attention away from pain: an experimental study.
Research on the effectiveness of distraction as a method of pain control is inconclusive. One mechanism pertains to the motivational relevance of distraction tasks. In this study the motivation to engage in a distraction task during pain was experimentally manipulated. Undergraduate students (N=73) participated in a cold pressor test (CPT) and were randomly assigned to three groups: a distraction-only group performed a tone-detection task during the CPT, a motivated-distraction group performed the same task and received a monetary reward for good task performance, and a control group did not perform the tone-detection task. Results indicated that engagement in the distraction task was better in the motivated-distraction group in comparison with the distraction-only group. Participants in both distraction groups experienced less pain compared to the control group. There were no overall differences in pain intensity between the two distraction groups. The effect of distraction was influenced by the level of catastrophic thinking about pain. For low catastrophizers, both distraction groups reported less pain as compared to the non-distracted control group. This was not the case for high catastrophizers. For high catastrophizers it mattered whether the distraction task was motivationally relevant: high catastrophizers reported less intense pain in the motivated-distraction group, as compared to the non-distracted control group. We conclude that increasing the motivational relevance of the distraction task may increase the effects of distraction, especially for those who catastrophize about pain.


Effects of dobutamine on cyclic AMP accumulation induced by the stimulation of dopamine receptors in rabbit retina in vitro.
Intact rabbit retinae were used for testing in vitro the potential activation of dopamine receptors by a new cardioactive sympathetic amine dobutamine. It was found that despite the structure relationship of dobutamine with other dopamine-analog, the pharmacological action of this compound is not comparable to that of apomorphine, N-methyl-dopamine and/or ADTN.


SNVPhyl: a single nucleotide variant phylogenomics pipeline for microbial genomic epidemiology.
The recent widespread application of whole-genome sequencing (WGS) for microbial disease investigations has spurred the development of new bioinformatics tools, including a notable proliferation of phylogenomics pipelines designed for infectious disease surveillance and outbreak investigation. Transitioning the use of WGS data out of the research laboratory and into the front lines of surveillance and outbreak response requires user-friendly, reproducible and scalable pipelines that have been well validated. Single Nucleotide Variant Phylogenomics (SNVPhyl) is a bioinformatics pipeline for identifying high-quality single-nucleotide variants (SNVs) and constructing a whole-genome phylogeny from a collection of WGS reads and a reference genome. Individual pipeline components are integrated into the Galaxy bioinformatics framework, enabling data analysis in a user-friendly, reproducible and scalable environment. We show that SNVPhyl can detect SNVs with high sensitivity and specificity, and identify and remove regions of high SNV density (indicative of recombination). SNVPhyl is able to correctly distinguish outbreak from non-outbreak isolates across a range of variant-calling settings, sequencing-coverage thresholds or in the presence of contamination. SNVPhyl is available as a Galaxy workflow, Docker and virtual machine images, and a Unix-based command-line application. SNVPhyl is released under the Apache 2.0 license and available at http://snvphyl.readthedocs.io/ or at https://github.com/phac-nml/snvphyl-galaxy.


Comparative antigenicity and potency of allergenic extracts from pollen and anthers.
Two hundred and twenty-six patients were scratch tested over a 10-month period with the pollen and anthers of six common hay fever plants. The results indicate that anthers and anther parts as "contaminant" material in pollen used in the manufacture of allergenic pollen products should be re-evaluated; it may be inappropriate to classify such parts as "foreign materials." They may be more fully utilized in the harvesting, extraction and administration of antigenic products for hyposensitization treatment, particularly for those hay fever producing plants where collection of pure pollen is particularly difficult.


Opioid-Prescribing Patterns in Connecticut and New Jersey Following Third Molar Extractions.
In recent years, opioid misuse has resulted in much scrutiny on providers' prescribing habits. The purpose of this study was to analyze prescribing habits in the context of third molar extractions as a model for promoting better postsurgical pain management. This was a cross-sectional survey of oral maxillofacial surgeons in Connecticut and New Jersey. A total of 291 practitioners were contacted to complete an online survey using Qualtrics Research Services to determine prescribing habits following third molar extractions. The most common approach for postoperative analgesia was nonsteroidal anti-inflammatory drugs (NSAIDs) and an opioid/acetaminophen (APAP) combination as 2 separate prescriptions, reported by 36% of participants. The combination of hydrocodone/APAP was the most common opioid formulation, and an average of 10.93 ± 4.51 opioid pills were prescribed with a maximum of 20 pills reported. Most providers (79%) consistently provided patients with opioid information. Only 22% reported always checking opioid-monitoring programs; however, providers were more likely to check if prescribing more than ∼11 opioid pills (P = .0228). Most reported using dexamethasone (82%) and bupivacaine (56%) intraoperatively, while ketorolac was less common (15%). No association was found between the quantity of opioids prescribed and the use of intraoperative ketorolac, steroids, or bupivacaine (P > .05). There remains to be a universal standard for using opioids for postoperative pain management in dentistry. Providers should be mindful when prescribing opioids and consider using NSAIDs and APAP for baseline pain plus a separate opioid prescription for breakthrough pain. Additional focus on minimizing the quantity of opioids prescribed and self-reflecting on prescribing and practice habits to further reduce opioid-related complications is warranted.


[The evaluation of academic emergency department design].
In our study which was based upon a questionnaire, the inner and outer architectural designs of emergency services of Emergency Medicine Departments were investigated. In this descriptive study, a standard questionnaire was sent to 26 Emergency Medicine Departments which were operating at that time. In the questionnaire, the internal, external architectural and functional features were questioned. Answers of 22 Emergency Medicine Departments were analysed. Two Emergency Medicine Departments that were not operating at that time were not included in the study. The analysis of the replies revealed that only 59% (n=13) of the Emergency Medicine Departments were designed as an emergency service prior to the construction. The ambulance parking areas were not suitable in 77% of the emergency units while only 54.5% (n=12) had protection against adverse weather conditions. In only 59% (n=13) of the emergency units, a triage unit was present and in only one of the in only one (4.5%), a decontamination room was available. It was understood that only 32% (n=8) of the emergency units were appropriate in enlarging their capacity taking the local risk factors into consideration. There was a toilette for disabled patients in only 18% (n=4) of the units as well. Considering a 12-year of history of the Emergency Medicine in Turkey, the presence of a lecture room is still 68% (n=15) in emergency departments which reflects that academic efforts in this field is emerging in challenging physical conditions. The results of our study revealed that emergency service architecture was neglected in Turkey and medical care given was precluded by the insufficient architecture. The design of emergency services has to be accomplished under guidance of scientific data and rules taking advices of architects who have knowledge and experience on this field.


Noncovalent and covalent functionalization of a (5, 0) single-walled carbon nanotube with alanine and alanine radicals.
We have systematically investigated the noncovalent and covalent adsorption of alanine and alanine radicals, respectively, onto a (5, 0) single-walled carbon nanotube using first-principles calculation. It was found that XH···π (X = N, O, C) interactions play a crucial role in the non-ovalent adsorption and that the functional group close to the carbon nanotube exhibits a significant influence on the binding strength. Noncovalent functionalization of the carbon nanotube with alanine enhances the conductivity of the metallic (5, 0) nanotube. In the covalent adsorption of each alanine radical onto a carbon nanotube, the binding energy depends on the adsorption site on CNT and the electronegative atom that binds with the CNT. The strongest complex is formed when the alanine radical interacts with a (5, 0) carbon nanotube through the amine group. In some cases, the covalent interaction of the alanine radical introduces a half-filled band at the Fermi level due to the local sp (3) hybridization, which modifies the conductivity of the tube.


COVID-19 and Other Pandemics: How Might They Be Prevented?
Pandemics such as influenza, smallpox, and plague have caused the loss of hundreds of millions of lives and have occurred for many centuries. Fortunately, they have been largely eliminated by the use of vaccinations and drugs. More recently, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and now Coronavirus Disease 2019 (COVID-19) have arisen, and given the current absence of highly effective approved vaccines or drugs, brute-force approaches involving physical barriers are being used to counter virus spread. A major basis for physical protection from respiratory infections is eye, nose, and mouth protection. However, eye protection with goggles is problematic due to "fogging", while nose/mouth protection is complicated by the breathing difficulties associated with non-valved respirators. Here, we give a brief review of the origins and development of face masks and eye protection to counter respiratory infections on the basis of experiments conducted 100 years ago, work that was presaged by the first use of personal protective equipment, "PPE", by the plague doctors of the 17th Century. The results of the review lead to two conclusions: first, that eye protection using filtered eye masks be used to prevent ocular transmission; second, that new, pre-filtered, valved respirators be used to even more effectively block viral transmission.


Adoption of Telehealth: Remote Biometric Monitoring Among Peritoneal Dialysis Patients in the United States.
We examined participant uptake and utilization of remote monitoring devices, and the relationship between remote biometric monitoring (RBM) of weight (Wt) and blood pressure (BP) with self-monitoring requirements. Participants on peritoneal dialysis (PD) (n = 269) participated in a Telehealth pilot study of which 253 used remote monitoring of BP and 255 for Wt. Blood pressure and Wt readings were transmitted in real time to a Telehealth call center, which were then forwarded to the PD nurses for real-time review. Uptake of RBM was substantial, with 89.7% accepting RBM, generating 74,266 BP and 52,880 Wt measurements over the study period. We found no significant correlates of RBM uptake with regard to gender, marital, educational, socio-economic or employment status, or baseline experience with computers; frequency of use of BP RBM by Black participants was less than non-Black participants, as was Wt RBM, and participants over 55 years old were more likely to use the Wt RBM than their younger counterparts. Having any review of the breach by a nurse was associated with reduced odds of a subsequent BP breach after adjusting for sex, age, and race. Remote biometric monitoring was associated with adherence to self-monitoring BP and Wt requirements associated with PD. Remote biometric monitoring was feasible, allowing for increased communication between patient and PD clinical staff with real-time patient data for providers to act on to potentially improve adherence and outcomes.


Improving Genomic Prediction in Cassava Field Experiments Using Spatial Analysis.
Cassava (Manihot esculenta Crantz) is an important staple food in sub-Saharan Africa. Breeding experiments were conducted at the International Institute of Tropical Agriculture in cassava to select elite parents. Taking into account the heterogeneity in the field while evaluating these trials can increase the accuracy in estimation of breeding values. We used an exploratory approach using the parametric spatial kernels Power, Spherical, and Gaussian to determine the best kernel for a given scenario. The spatial kernel was fit simultaneously with a genomic kernel in a genomic selection model. Predictability of these models was tested through a 10-fold cross-validation method repeated five times. The best model was chosen as the one with the lowest prediction root mean squared error compared to that of the base model having no spatial kernel. Results from our real and simulated data studies indicated that predictability can be increased by accounting for spatial variation irrespective of the heritability of the trait. In real data scenarios we observed that the accuracy can be increased by a median value of 3.4%. Through simulations, we showed that a 21% increase in accuracy can be achieved. We also found that Range (row) directional spatial kernels, mostly Gaussian, explained the spatial variance in 71% of the scenarios when spatial correlation was significant.


Conflict monitoring in the human anterior cingulate cortex during selective attention to global and local object features.
Parallel processing affords the brain many advantages, but processing multiple bits of information simultaneously presents formidable challenges. For example, while one is listening to a speaker at a noisy social gathering, processing irrelevant conversations may lead to the activation of irrelevant perceptual, semantic, and response representations that conflict with those evoked by the speaker. In these situations, specialized brain systems may be recruited to detect and resolve conflict before it leads to incorrect perception and/or behavior. Consistent with this view, recent findings indicate that dorsal/caudal anterior cingulate cortex (dACC), on the medial walls of the frontal lobes, detects conflict between competing motor responses primed by relevant versus irrelevant stimuli. Here, we used a cued global/local selective attention task to investigate whether the dACC plays a general role in conflict detection that includes monitoring for conflicting perceptual or semantic representations. Using event-related functional magnetic resonance imaging (fMRI), we found that the dACC was activated by response conflict in both the global and the local task, consistent with results from prior studies. However, dACC was also activated by perceptual and semantic conflict arising from global distracters during the local task. The results from the local task have implications for recent theories of attentional control in which the dACC's contribution to conflict monitoring is limited to response stages of processing, as well as for our understanding of clinical disorders in which disruptions of attention are associated with dACC dysfunction.


Controlled trial of amitriptyline in general practice.
A controlled double-blind trial of amitriptyline at two dosage levels (75 and 150 mg/day), amylobarbitone (150 mg/day), and an inert substance for a period of four weeks was conducted on four matched groups of women attending their general practitioners and suffering from a depressive illness. Improvement at 7 and 28 days was noted on several measures of depression and anxiety in all treatment groups. Of these treatments amitriptyline 150 mg/day was the most consistent in relieving depression and anxiety. Troublesome side effects were equally distributed among the four treatments.


Sequential "click" functionalization of mesoporous titania for energy-relay dye enhanced dye-sensitized solar cells.
Energy relay dyes (ERDs) have been investigated previously as a mean to achieve panchromatic spectral response in dye-sensitized solar cells via energy transfer. To reduced the distance between the ERDs and energy-accepting injection dyes (IDs) on the surface of a mesoporous titanium dioxide electrode, the ERDs were immobilized adjacent to the IDs via a sequential functionalization approach. In the first step, azidobenzoic acid molecules were co-adsorbed on the mesoporous titanium dioxide surface with the ID. In the second step, the highly selective copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition "click" reaction was employed to couple an alkyne-functionalized ERD to the azidobenzoic acid monolayer. The cycloaddition step in the mesoporous electrode was slowed dramatically due to reactants and catalysts forming agglomerates. In solar cell devices, the close proximity between the surface-immobilized ERD and energy-accepting squaraine sensitizer dyes results in energy transfer efficiencies of up to 91%. The relative improvement in device performance due to the additional ERD spectral response was 124%, which is among the highest reported. The sequential functionalization approach described herein is transferrable to other applications requiring the functionalization of electrodes with complex molecules.


Ionophore-based pH independent detection of ions utilizing aggregation-induced effects.
Ionophores have been integrated into various electrochemical and optical sensing platforms for the selective detection of ions. Previous ionophore-based optical sensors rely on a H+ chromoionophore as the signal transducer and consequently, suffered from a pH cross-response. pH independent methods were proposed very recently by utilizing the solvatochromic dyes or the exhaustive mode. Here, we report a pH independent sensing principle based on nanospheres containing ionophores. As the ion-exchange occurs, the signal transducer undergoes aggregation-induced emission (AIE) or aggregation-caused quenching (ACQ), leading to a dramatic change in fluorescence intensity. The principle was evaluated on different ionophores including those selective for K+, Na+, Ca2+, and Pb2+. The nanospheres were also introduced into microfluidic chips and successfully applied for the determination of sodium and potassium ion concentrations in diluted blood serum and urine samples.


Sensitivity Improvement of Highly Stretchable Capacitive Strain Sensors by Hierarchical Auxetic Structures.
Highly stretchable sensors that can detect large strains are useful in deformable systems, such as soft robots and wearable devices. For stretchable strain sensors, two types of sensing methods exist, namely, resistive and capacitive. Capacitive sensing has several advantages over the resistive type, such as high linearity, repeatability, and low hysteresis. However, the sensitivity (gauge factor) of capacitive strain sensors is theoretically limited to 1, which is much lower than that of the resistive-type sensors. The objective of this study is to improve the sensitivity of highly stretchable capacitive strain sensors by integrating hierarchical auxetic structures into them. Auxetic structures have a negative Poisson's ratio that causes increase in change in capacitance with applied strains, and thereby improving sensitivity. In order to prove this concept, we fabricate and characterize two sensor samples with planar dimensions 60 mm × 16 mm. The samples have an acrylic elastomer (3M, VHB 4905) as the dielectric layer and a liquid metal (eutectic gallium-indium) for electrodes. On both sides of the sensor samples, hierarchical auxetic structures made of a silicone elastomer (Dow Corning, Sylgard 184) are attached. The samples are tested under strains up to 50% and the experimental results show that the sensitivity of the sensor with the auxetic structure exceeds the theoretical limit. In addition, it is observed that the sensitivity of this sensor is roughly two times higher than that of a sensor without the auxetic structure, while maintaining high linearity (R 2 = 0.995), repeatability (≥104 cycles), and low hysteresis.


[Blood grouping in mixed blood stains and excretions].
Blood grouping in mixed blood stains and excretions can often be a problem. It is related with the fact that, when blood and excretions of persons having different groups get mixed, the determinants of blood antigens of one person interact with the active centers of excretions' antibodies of another one and vice versa. The authors suggest a method to do away with the phenomenon.


The 56-kilodalton major protein antigen of Rickettsia tsutsugamushi: molecular cloning and sequence analysis of the sta56 gene and precise identification of a strain-specific epitope.
Lasting immunity against Rickettsia tsutsugamushi, the causative agent of scrub typhus fever, has been demonstrated to be strain specific. Two protein antigens of 110 and 56 kilodaltons (kDa) have been shown to exhibit strain-specific epitopes. The 56-kDa scrub typhus antigen (Sta56) is an abundant outer membrane protein of R. tsutsugamushi and is an antigen often recognized by humans infected with this obligate intracellular bacterium. In this study the complete gene encoding Sta56 (strain Karp) was cloned into pBR322 on a 2.3-kilobase genomic HindIII DNA fragment and the complete 56-kDa polypeptide was expressed in Escherichia coli. DNA sequence analysis of the 2.3-kilobase HindIII fragment revealed an open reading frame large enough to encode a 56-kDa polypeptide. A putative signal sequence was identified at the deduced amino terminus of the Sta56 polypeptide, and pulse-chase analysis of maxicells labeled with [35S]methionine demonstrated that a higher-molecular-weight precursor matures into the 56-kDa polypeptide. Epitope scanning analysis with synthetic peptides derived from the deduced amino acid sequence identified an octapeptide (located from amino acid residues 117 to 124) that was reactive with a Karp strain-specific monoclonal antibody (K13F88A). Other epitopes recognized by different monoclonal antibodies, including another Karp strain-specific monoclone (K1E106), were localized to different regions of the protein based on their reactivities with lambda gt11 recombinants expressing various portions of the sta56 gene.


Diversity of circumsporozoite antigen genes from two strains of the malarial parasite Plasmodium knowlesi.
The complete nucleotide sequence of the coding region of the circumsporozoite antigen gene (CS gene) of the Nuri strain of the malarial parasite Plasmodium knowlesi is presented. The gene from the Nuri strain exhibits a novel form of sequence diversity when compared to the CS gene from the H strain. Instead of the 12 tandem repeating 36-base pair units of the H strain, the Nuri strain contains 16 tandem repeating 27-base pair units of a different nucleotide sequence that encodes a different repeating peptide. In contrast, the 5' and 3' coding and noncoding sequences flanking the repeats are 98 percent conserved in both strains.


Altered Dynamic Functional Network Connectivity in Healthy Adults with Acute Pain: Findings from the Human Connectome Project.
Characterizing the neural signature of pain and its modulation is critical for assessing treatment efficacy and conducting translational clinical research. However, the dynamics of pain processing in the brain have remained largely unknown. In this study, we employed independent component analysis (ICA) as a data-driven clustering method on resting-state functional magnetic resonance imaging (fMRI) to obtain intrinsic connectivity networks (ICNs) in a cohort of healthy adults from the Human Connectome Project (HCP) who were identified as having acute pain. We examined the temporal dynamic functional network connectivity (dFNC) with sliding time window correlation and k-means clustering, and compared dFNC state properties and meta-state metrics between groups. Results showed that acute pain had a significant impact on dFNC in a common connectivity state (dynamic state 5) among several ICN pairs, including the salience network, default mode network, central executive, dorsal attention networks, and basal ganglia (false discovery rate [FDR]-corrected p of 0.05). Furthermore, healthy adults with and without acute pain exhibited differences in mean dwell time (dynamic state 3), which indicated that individuals with acute pain spent more time in particular states than those without pain. Meta-state dynamic analysis further indicated significant group differences in the number of states (i.e., unique time windows for each subject), changes between states (i.e., number of times each subject changes from one meta-state to other), and total travelled distances. These preliminary results provide new information about time-varying properties of pain states related to acute pain and advocate for further state-based analyses of pain for future pain biomarker discovery and development.


Role of misalignment-induced angular chirp in the electro-optic detection of THz waves.
A general description of electro-optic detection including non-collinear phase matching and finite transverse beam profiles is presented. It is shown theoretically and experimentally that non-collinear phase matching in ZnTe (and similar materials) produces an angular chirp in the χ(2)-generated optical signal. Due to this, in non-collinear THz and probe arrangements such as single-shot THz measurements or through accidental misalignment, measurement of an undistorted THz signal is critically dependent on having sufficient angular acceptance in the optical probe path. The associated spatial walk-off can also preclude the phase retardation approximation used in THz-TDS. The rate of misalignment-induced chirping in commonly used ZnTe and GaP schemes is tabulated, allowing ready analysis of a detection system.


Pathology and compensation during visual signal processing in schizophrenia--spatial analysis of event-related potentials.
Correlations between measures of attention and topographical abnormalities of evoked cortical potentials elicited during the Continuous Attention Test (CAT) were assessed in 50 schizophrenic patients, compared to 50 healthy subjects. For each group and for each CAT condition evoked responses consisted of six successive epochs (segments) of stable spatially configured potentials. Quantitative descriptors of those configurations (Lehmann 1987) were referred to the CAT data. In patients: (1) segments III-V were delayed, (2) in the non-target condition, diminished global field power (GFP) emerged, coexisting either with lower amplitude of posterior potentials in segment I and II or with lower amplitude of a central positive potential in segment V, (3) an altered topographic pattern of responses to the target stimulus occurred. In healthy subjects detection of the target (as compared to the non-target condition) was associated with a shift of the location of the positive potential in segments IV and V from a central towards the prefrontal area. In patients, in segment V a similar shift reached frontal, but not prefrontal areas, and additionally, the central areas remained active. Delayed latency and low GFP in segment V in the non-target condition in patients correlated with poor CAT performance. A more posterior location of the positive centroid in segment V during detection of the target correlated with better CAT results, and the associated GFP increase with less prolonged reaction time. The data revealed a possible compensatory role of central and frontal areas in the face of weakened prefrontal functions in schizophrenia.


A prospective epidemiological analysis of controlling nutritional status score with the poor functional outcomes in Chinese patients with haemorrhagic stroke.
Nutritional Risk Screening index is a standard tool to assess nutritional risk, but epidemiological data are scarce on controlling nutritional status (CONUT) as a prognostic marker in acute haemorrhagic stroke (AHS). We aimed to explore whether the CONUT may predict a 3-month functional outcome in AHS. In total, 349 Chinese patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. The cohort patients were divided into high-CONUT (≥ 2) and low-CONUT (< 2) groups, and primary outcomes were a poor functional prognosis defined as the modified Rankin Scale (mRS) score of ≥ 3 at post-discharge for 3 months. Odds ratios (OR) with 95 % confidence intervals (CI) for the poor functional prognosis at post-discharge were estimated by using a logistic analysis with additional adjustments for unbalanced variables between the high-CONUT and low-CONUT groups. A total of 328 patients (60·38 ± 12·83 years; 66·77 % male) completed the mRS assessment at post-discharge for 3 months, with 172 patients at malnutrition risk at admission and 104 patients with a poor prognosis. The levels of total cholesterol and total lymphocyte counts were significantly lower in high-CONUT patients than low-CONUT patients (P = 0·012 and < 0·001, respectively). At 3-month post discharge, there was a greater risk for the poor outcome in the high-CONUT compared with the low-CONUT patients at admission (OR: 2·32, 95 % CI: 1·28, 4·17). High-CONUT scores independently predict a 3-month poor prognosis in AHS, which helps to identify those who need additional nutritional managements.


The Caenorhabditis elegans LET-418/Mi2 plays a conserved role in lifespan regulation.
The evolutionarily conserved nucleosome-remodeling protein Mi2 is involved in transcriptional repression during development in various model systems, plays a role in embryonic patterning and germ line development, and participates in DNA repair and cell cycle progression. It is the catalytic subunit of the nucleosome remodeling and histone deacetylase (NuRD) complex, a key determinant of differentiation in mammalian embryonic stem cells. In addition, the Drosophila and C. elegans Mi2 homologs participate in another complex, the MEC complex, which also plays an important developmental role in these organisms. Here we show a new and unexpected feature of the C. elegans Mi2 homolog, LET-418/Mi2. Lack of LET-418/Mi2 results in longevity and enhanced stress resistance, a feature that we found to be conserved in Drosophila and in Arabidopsis. The fact that depletion of other components of the NuRD and the MEC complexes did not result in longevity suggests that LET-418 may regulate lifespan in a different molecular context. Genetic interaction studies suggest that let-418 could act in the germ-cell-loss pathway, downstream of kri-1 and tcer-1. On the basis of our data and on previous findings showing a role for let-418 during development, we propose that LET-418/Mi2 could be part of a system that drives development and reproduction with concomitant life-reducing effects later in life.


Separate roles for Med12 and Wnt signaling in regulation of oxytocin expression.
Transcriptional control of oxytocinergic cell development influences social, sexual, and appetite related behaviors and is implicated in disorders such as autism and Prader-Willi syndrome. Mediator 12 (Med12) is a transcriptional coactivator required for multiple facets of brain development including subsets of serotonergic and dopaminergic neurons. We surveyed hormone gene expression within the hypothalamo-pituitary axis of med12 mutant zebrafish embryos with a focus on oxytocin (oxt) expression. Some transcripts, such as oxt, vasopressin (avp) and corticotrophin releasing hormone (crh) are undetectable in the med12 mutant, while others are upregulated or downregulated to varying degrees. In med12 mutants, the expression patterns of upstream transcriptional regulators of oxytocinergic cell development remain largely intact in the pre-optic area, suggesting a more direct influence of Med12 on oxt expression. We show that Med12 is required for Wnt signaling in zebrafish. However, oxt expression is unaffected in Wnt-inhibited embryos indicating independence of Wnt signaling. In fact, overactive Wnt signaling inhibits oxt expression, and we identify a Wnt-sensitive period starting at 24 h post fertilization (hpf). Thus, Med12 and repression of Wnt signaling display critical but unrelated roles in regulating oxt expression.


Evaluating 17 methods incorporating biological function with GWAS summary statistics to accelerate discovery demonstrates a tradeoff between high sensitivity and high positive predictive value.
Where sufficiently large genome-wide association study (GWAS) samples are not currently available or feasible, methods that leverage increasing knowledge of the biological function of variants may illuminate discoveries without increasing sample size. We comprehensively evaluated 17 functional weighting methods for identifying novel associations. We assessed the performance of these methods using published results from multiple GWAS waves across each of five complex traits. Although no method achieved both high sensitivity and positive predictive value (PPV) for any trait, a subset of methods utilizing pleiotropy and expression quantitative trait loci nominated variants with high PPV (>75%) for multiple traits. Application of functionally weighting methods to enhance GWAS power for locus discovery is unlikely to circumvent the need for larger sample sizes in truly underpowered GWAS, but these results suggest that applying functional weighting to GWAS can accurately nominate additional novel loci from available samples for follow-up studies.


Influence of high protein diets on cartilage and bone formation in rats.
The influence of diets containing combinations of high protein and low calcium on discrete stages of bone formation was investigated in 28-day-old rats. A bone matrix-induced bone forming system was utilized to determine the stages of endochondral ossification that were being affected. Mesenchymal cell proliferation as assessed by [3H]-thymidine incorporation and ornithine decarboxylase activity were unchanged in animals fed a high protein (80% casein)/normal calcium (0.61% Ca; 0.40% P) diet. However, osteogenesis was reduced by 78% in the rats fed high protein/normal calcium as measured by 45Ca incorporation. Alkaline and acid phosphatase activities in bone were increased 2.5 and 2.3 times, respectively, reflecting increased matrix turnover induced by the high protein availability. Bone that did form was not remodeled nor was there evidence of marrow formation. The animals were normocalcemic and normophosphatemic and showed no evidence of acidosis. A combination diet of high protein and low calcium resulted in a 62% reduction of cell proliferation and chondrogenesis and a 98% inhibition of bone formation. High dietary protein-induced osteoporosis in animals is due to a failure of osteogenesis of the stage of ossification possibly a result of restricted availability of calcium at the site of mineralization.


Protective effect of Agave americana Linn. leaf extract in acetic acid-induced ulcerative colitis in rats.
Natural plants always provide core compounds for new drug development. In the present life and food style, inflammatory bowel disease has become common and needs a lead compound for its drug development. To evaluate the effect of Agave americana Linn. leaf extract in acetic acid-induced ulcerative colitis in rats based on its traditional anti-inflammatory use. Male Wistar rats were pretreated with A. americana leaf extract in the dose of 200 and 400 mg/kg p.o. daily for 7 days. On 8(th) day, 2 ml of 4% v/v acetic acid in saline was instilled into rats' rectum. Prednisolone was used as standard drug and it was administered on the day of acetic acid instillation and continued for 3 days. Extract treatment was continued till 11(th) day. Body weight, ulcer score, colonic muscle contraction, antioxidant activity and histopathology were studied. Statistical analysis was performed using Parametric one-way analysis of variance followed by Tukey's posttest. A. americana have retained total body weight significantly (P < 0.01) and decreased colon weight/length ratio. Extract have shown a significant decrease (P < 0.001) in ulcer scores, myeloperoxidase, lipid peroxidase activity. Further, extract have shown significant improvement in colonic muscle contraction, histopathology of colon etc., which is comparable with standard drug. A. americana possess protective effect against acetic acid-induced colitis in rats.


Peripheral vascular pathophysiology of Plasmodium berghei infection: a comparative study in the cheek pouch and brain of the golden hamster.
Four- to six-week-old hamsters were infected with 1.5 X 10(7) Plasmodium berghei-parasitized hamster red blood cells by intraperitoneal injection. Cheek pouch circulation was observed microscopically in the anesthetized animal; the brain and contralateral pouch were collected for histopathologic examination on days 3-12 post-challenge. Cheek pouch vascular lesions, observed in vivo, appear to involve three phenomena; early (beginning 3-4 days) adhesion of pigment-laden mononuclear cells to endothelium within venous vessels and loss of function of the small capillaries supplying the skeletal muscle fibers and, later (6-9 days), the apparent attraction of erythrocytes to venular and venous endothelium and to adherent monocytes. The aggregation of formed elements on endothelial walls leads to progressive occlusion of venules and small veins and contributes to the observed disruption of flow through capillary networks. Histopathology of the brain and pouch shows vascular changes similar to those seen in vivo; in addition, multifocal hemorrhages are seen commonly in the brain and occasionally in the pouch on postmortem. In severe disease, evidence of cerebral edema is seen in the brain. The data suggest that failure of capillary flow and disruption of venous outflow tracts by cell aggregates are central to vascular failure in both the cheek pouch and brain of the P. berghei infected hamster. This hamster model of human cerebral malaria allows the in vivo observation, still and video photomicrography, and manipulation of the peripheral vascular pathogenesis of a disease process similar to that seen in humans.


Effect of six sigma program on the number of surgeries cancellation.
Today, the rate of surgeries is increasing, but surgeries are canceled due to various reasons. Unexpected cancellation of surgeries not only results in disorder in the operating room schedule, but also causes stress for patients and their family and increases costs. We determined the number and causes of surgery cancellations and areas for improvement. This outcome evaluation of Six Sigma program was conducted on 850 cases after the implementation of the program and compared to that of 850 cases which received routine care before the program. Cases were selected through easy sampling during the study. Before the implementation, the number of cancellations was recorded daily and their reasons were investigated. Then, Six Sigma program was implemented in accordance with the reasons for each category and necessary steps were taken to prevent the cancellation of surgeries. Data were collected for 3 months using a three-section data collection form. For data analysis, distribution and relative frequency and chi-square test were used. The three categories of patient, physician, and hospital system were identified as the main causes. The highest rate of cancellation was related to ENT surgeries (74.19%). No cancellations were made in orology surgeries. The implementation of the Six Sigma program caused a significant difference in surgery cancellation (P = 0.003); 31 (3.6%) cases of cancellation were reduced to 12 (1.4%) cases. The results showed that Six Sigma program is a pre-surgery care quality improvement program. Patient education and the implementation of the 6 sigma program can be effective in reducing the rate of cancellation of operations.


Short-term interval exercise suppresses acylated ghrelin and hunger during caloric restriction in women with obesity.
Caloric restriction is suggested to increase hunger, in part, through complex interactions of hormones and behavior that contribute to challenges in long-term weight loss. Although intense exercise may attenuate appetite, no data exist testing the effects of interval exercise (INT) during a low-calorie diet (LCD) on appetite regulation. We hypothesized that LCD+INT would favorably influence satiety when compared with an energy-deficit matched LCD in women with obesity. Twenty-six women with obesity (47.3±2.4 yrs; 37.3 ± 1.2 kg/m2) were randomized to either LCD (n = 13; mixed meals of ~1200 kcal/d) or LCD+INT (n = 13; 60 min/d of supervised interval exercise at 90% HRpeak for 3 min and 50% HRpeak for 3 min) for 2 weeks. An additional 350kcal (shake) was provided to LCD+INT individuals post-exercise to equate energy availability between groups. Total PYY, acylated ghrelin and des-ghrelin were measured at 0, 30 and 60 min of a 75g OGTT before and after the intervention. Visual analog scales were also administered at 0 and 120 min of the OGTT to assess appetite perception. Food logs were recorded prior to and during the intervention to ensure caloric intake compliance. Compared with pre-intervention conditions, both interventions decreased food intake (P = 0.001) and body fat (P < 0.01). There was no effect on fasting PYY, but both LCD and LCD+INT increased post-prandial PYY iAUC (P < 0.001) relative to pre-intervention. LCD+INT maintained fasting acylated ghrelin (P = 0.06) and suppressed post-prandial acylated ghrelin iAUC (P = 0.04) compared to LCD. Neither intervention impacted circulating des- ghrelin before or following the OGTT. Interestingly, LCD+INT attenuated fasting hunger and maintained fullness compared with LCD (P = 0.05 and P = 0.06, respectively). Taken together, interval exercise favors acylated ghrelin suppression and perception of hunger during a LCD in women with obesity.


Newborn Screening Policy Decisions: Adding Conditions.
Policy decisions about mandated newborn screening should be based on scientific evidence and incorporate expert opinion. At the national level, a systematic evidence review evaluates the benefit of screening for disorders that may be added to the Recommended Uniform Screening Panel, and ultimately considered by individual newborn screening programs. Recent changes in state laws, including in North Carolina, are intended to streamline the decision-making process for newborn screening policy changes.