Estimating proportion of days covered (PDC) using real-world online medicine suppliers' datasets.
The proportion of days covered (PDC) is used to estimate medication adherence by looking at the proportion of days in which a person has access to the medication, over a given period of interest. This study aimed to adapt the PDC algorithm to allow for plausible assumptions about prescription refill behaviour when applied to data from online pharmacy suppliers. Three PDC algorithms, the conventional approach (PDC1) and two alternative approaches (PDC2 and PDC3), were used to estimate adherence in a real-world dataset from an online pharmacy. Each algorithm has different denominators and increasing levels of complexity. PDC1, the conventional approach, is the total number of days between first dispensation and a defined end date. PDC2 counts the days until the end of supply date. PDC3 removes from the denominator specifically defined large gaps between refills, which could indicate legitimate reasons for treatment discontinuation. The distribution of the three PDCs across four different follow-up lengths was compared. The dataset included people taking ACE inhibitors (n = 65,905), statins (n = 100,362), and/or thyroid hormones (n = 30,637). The proportion of people taking ACE inhibitors with PDC ≥ 0.8 was 50-74% for PDC1, 81-91% for PDC2, and 86-100% for PDC3 with values depending on drug and length of follow-up. Similar ranges were identified in people taking statins and thyroid hormones. These algorithms enable researchers and healthcare providers to assess pharmacy services and individual levels of adherence in real-world databases, particularly in settings where people may switch between different suppliers of medicines, meaning an individual supplier's data may show temporary but legitimate gaps in access to medication. Accurately identifying problems with adherence provides the foundation for opportunities to improve experience, adherence and outcomes and to reduce medicines wastage. Research with people taking medications and prescribers is required to validate the algorithms' assumptions.


Differential scanning calorimetry of rat liver mitochondria.
Differential scanning calorimetry was employed for studying rat liver mitochondria and extracted mitochondrial lipids. Endothermic transition in the range 15--40 degrees C was detected for the whole mitochondria and between 10--20 degrees C for the extracted lipids.


Characterization of the cardiac myosin binding protein-C phosphoproteome in healthy and failing human hearts.
Cardiac myosin binding protein-C (cMyBP-C) becomes dephosphorylated in the failing heart and reduced phosphorylation-dependent regulation of cMyBP-C has been implicated in contractile dysfunction. To date, several phosphorylation sites have been identified for human cMyBP-C; however, a comprehensive characterization of the cMyBP-C phosphoproteome is lacking. This study aimed to characterize the cMyBP-C phosphoproteome using two different proteomic-based methods in explanted donor and end-stage failing hearts. The first approach used to characterize the cMyBP-C phosphoproteome employed a strong-cation exchange chromatography (SCX) fractionation method (10 pooled samples, technical replicates=4) and the second employed a sodium dodecylsulfate polyacrylamide gel electrophoresis method (n=10; technical replicates=2). Each subsequently underwent titanium dioxide (TiO2) affinity chromatography to enrich for the tryptic phosphopeptides, which were analyzed using an LTQ-Orbitrap mass spectrometer. Moreover, recombinant C0-C2 fragment of mouse cMyBP-C incubated with PKA, PKC, CaMKII and CK2 was analyzed to identify the kinases involved with phosphorylation of cMyBP-C. Seventeen phosphorylation sites on cMyBP-C were identified in vivo, with the majority localized in the N-terminal domains C0-C2. The three most abundant phosphorylated sites, Ser284, Ser286 and Thr290, are located in the regulatory M-domain of cMyBP-C. Ser284 showed a significant reduction in phosphorylation in HF. This study demonstrates that cMyBP-C harbors more phosphorylation sites than previously known, with a total of 17 (9 novel) identified phosphorylation sites in vivo. Most sites were primarily located within the N-terminal side of the protein. The most highly phosphorylated site on cMyBP-C was Ser284 and this site showed decreased phosphorylation in the failing heart, which implicates importance for fine-tuning contractility. To date, the functional importance of Ser286 and Thr290 is unknown. In addition, 16 sites were identified after in vitro kinase incubation. The data have been deposited to the ProteomeXchange with identifier PXD000158.


Novel linear triaryl guanidines, N-substituted guanidines and potential prodrugs as antiprotozoal agents.
A series of triaryl guanidines and N-substituted guanidines designed to target the minor groove of DNA were synthesized and evaluated as antiprotozoal agents. Selected carbamate prodrugs of these guanidines were assayed for their oral efficacy. The linear triaryl bis-guanidines 6a,b were prepared from their corresponding diamines 4a,b through the intermediate BOC protected bis-guanidines 5a,b followed by acid catalyzed deprotection. The N-substituted guanidino analogues 9c-f were obtained in three steps starting by reacting the diamines 4a,b with ethyl isothiocyanatoformate to give the carbamoyl thioureas 7a,b. Subsequent condensation of 7a,b with various amines in the presence of EDCI provided the carbamoyl N-substituted guanidine intermediates 8a-f which can also be regarded as potential prodrugs for the guanidino derivatives. Compounds 9c-f were obtained via the base catalyzed decarbamoylation of 8a-f. The DNA binding affinities for the target dicationic bis-guanidines were assessed by DeltaT(m) values. In vitro antiprotozoal screening of the new compounds showed that derivatives 6a, 9c and 9e possess high to moderate activity against Trypanosoma brucei rhodesiense (T.b.r.) and Plasmodium falciparum (P.f.). While the prodrugs did not yield cures upon oral administration in the antitrypanosomal STIB900 mouse model, compounds 8a and 8c prolonged the survival of the treated mice.


Experimental study on permeability characteristics and radon exhalation law of overburden soil in uranium tailings pond.
The permeability characteristics of overburden soil have a significant effect on radon exhalation in uranium tailings pond. To understand this change, the effects of dry density, particle size range, and moisture content on the gas permeability and radon exhalation were studied by correlation analysis method. According to the mechanism of radon generation, the permeability characteristics of overburden, and the weather conditions, a theoretical model of radon exhalation was constructed and an experimental setup was designed. A series of tests on different properties of overburden soil were conducted by uranium tailings permeameter, and the radon exhalation rate of corresponding overburden surface was measured by local static method. Results show that the permeability of overburden decreased, which led to the decrease of radon exhalation: (1) At the same moisture content, with the increase of dry density, both the gas permeability and radon exhalation rate decrease. (2) At the same moisture content, with the increase of the particle size range, both the gas permeability and radon exhalation rate increase. (3) At the same dry density, with the increase of moisture content, the gas permeability decreases, while the radon exhalation rate increases slightly at first and then decreases.


Brain tumors - other treatment modalities.
Management of tumors of the central nervous system is challenging for clinicians for various reasons, including complex diagnostic procedures, limited penetration of drugs into brain tissue, and the prerequisite to preserve brain function in any case of therapeutic intervention. Therapeutic success is dependent on the efforts, skills, and cooperation of involved specialists and disciplines. Knowledge and ability to apply adequate therapeutic modalities in an interdisciplinary approach in due time are crucial, necessitating coordination of diagnostic procedures and therapeutic interventions by means of multidisciplinary brain tumor boards. In this chapter we present in brief the essential current standards and future perspectives for therapy modalities that complement surgery of brain tumors.


Effect of coarctation on matrix content of experimental aortic atherosclerosis: relation to location, plaque size and blood pressure.
Cynomolgus monkeys were fed an atherogenic diet for 6 months following surgically produced high-grade (n = 10) or mild (n = 16) mid-thoracic aortic coarctation. A diet-control (DC) group (n = 13) was fed the diet without coarctation. High-grade coarctation (HGC) resulted in 74.1% +/- 8.3% stenosis by aortography prior to sacrifice and was associated with systolic brachial blood pressures of 143.3 +/- 26.0 mmHg and gradients across the stenoses of 36.8 +/- 23.6 mmHg. Mild coarctation (MC) resulted in stenoses of 50.9% +/- 12.9%, brachial systolic pressures of 119.4 +/- 25.7 and gradients of 12.5 +/- 15.2 mm Hg (P < 0.01, P = 0.03 and P < 0.005, respectively, compared with HGC). When total plaque cross-sectional area exceeded 0.8 mm2, the entire arterial circumference was usually involved. HGC resulted in complete sparing or minimal plaque formation in sections distal to the stenoses compared with proximal sections (P < 0.001). There were no significant differences between MC and DC animals in plaque location or size. Matrix content increased with plaque area regardless of degree of stenosis or sampling level (P < 0.01), but lesions with more than 75% matrix content were more numerous in distal than in proximal sections despite their smaller size. The number of plaques with greater than 75% matrix content was increased proximal to HGC (P < 0.04). Thus, distal location and plaque size were independent determinants of plaque matrix content and matrix content was increased proximal to HGC regardless of plaque size. Attempts to evaluate effects of various regimens and interventions on plaque composition need to take location and plaque size, as well as blood pressure differences, into account.


Angiographic findings in patients exhibiting ischemia after oral dipyridamole.
We have assessed the angiographic features of a group of 37 patients given oral dipyridamole and 37 patients given matching placebo. Both groups represented severe coronary arterial disease and were studied prior to bypass surgery. Six patients (16%) had angina and 13 patients (35%) had electrocardiographic changes after dipyridamole. All the patients in the control group were nonresponders. In the group given dipyridamole the patients responding with angina had significantly more compromised collaterals than the patients without chest pain (P = 0.021). The same applied to the patients with electrocardiographic changes versus those with no electrocardiographic changes (P = 0.034). No differences between responders and nonresponders could be found in terms of the severity of coronary arterial disease, severity of anginal symptoms, exercise tolerance, antianginal medication, number of past myocardial infarctions, and left ventricular ejection fraction. In conclusion, the data strongly suggest that ischaemic responses to dipyridamole originate from myocardial steal accentuated by compromised flow in collateral vessels.


A block at Man5GlcNAc2-pyrophosphoryldolichol in intact but not disrupted castanospermine and swainsonine-resistant Chinese hamster ovary cells.
A mutation in glycoprotein processing inhibitor-resistant (PIR) Chinese hamster ovary (CHO) cells was previously shown to result in a block at the Man5GlcNAc2 stage of the dolichol-oligosaccharide biosynthetic pathway (Lehrman, M.A., and Zeng, Y. (1989) J. Biol. Chem. 264, 1584-1593). These cells had normal mannose-P-dolichol synthase activity and were able to transfer the Man5GlcNAc2 oligosaccharides to protein. We have now characterized the mutation in greater detail. In PIR cells, biosynthesis of GDP-mannose and mannose-P-dolichol was normal, and pulse-chase analysis indicated that the rate of Man5GlcNAc2-P-P-dolichol formation in vivo was similar to that in parental CHO cells but without subsequent formation of larger intermediates. Cell fusion studies demonstrated that the PIR genotype was recessive and that PIR cells could complement the mutation in B4-2-1 cells, which fail to synthesize mannose-P-dolichol. In contrast to the results obtained with intact cells, incubation of membrane preparations of PIR cells with GDP-[3H]mannose resulted in the synthesis of intermediates containing up to 9 mannose residues, indicating that the cells contained active mannosyltransferases VI to IX. With a simplified assay for the formation of intermediates containing 6 to 9 mannoses, it was shown that physical disruption of PIR cells was able to eliminate the block at the pentamannosyl stage. Furthermore, although the temperature requirements of the reactions for the control CHO and PIR membranes were similar, Man5GlcNAc2-elongating activity in CHO membranes was inhibited by alkaline pH treatment, whereas this treatment irreversibly stimulated the activity in PIR membranes. Taken together, these results suggest that the PIR cells have a recessive defect, and that the missing gene product is required by mannosyltransferase VI in vivo for proper utilization of either mannose-P-dolichol or Man5GlcNAc2-P-P-dolichol. Since the defect was manifested in vivo but not in vitro, this requirement appears necessary for intact cells but not for disrupted cells or isolated membranes.


Selection of DNA binding sites by regulatory proteins. Functional specificity and pseudosite competition.
The frequency of base-pair occurrence in a set of recognition sequences for a particular DNA-binding protein is strongly related to the contributions to the binding free energy from the individual base pairs. Thus from the statistics of base-pair choice, it is possible to estimate the relative binding strengths of any base-pair sequences and to predict the effect of point mutations in specific sites. On the same basis, one can describe the binding properties of random DNA sequences and thereby the expected competitive effects from all the nonspecific DNA sites in the genome of a living cell. The statistical selection theory [Berg & von Hippel.J. Mol. Biol. 193 (1987) 723-750] describing these relations is extended and tested with computer simulations. The theory is shown to hold up well also in the case when base pairs contribute cooperatively to the binding interaction. The simulations also demonstrate the effects of the statistical small-sample uncertainty that appears due to the limited size of all sets of recognition sites identified.


Novel workflow for combining Raman spectroscopy and MALDI-MSI for tissue based studies.
Molecular heterogeneity of cancer is a major obstacle in tumor diagnosis and treatment. To deal with this heterogeneity, a multidisciplinary combination of different analysis techniques is of urgent need because a combination enables the creation of a multimodal image of a tumor. Here, we develop a computational workflow in order to combine matrix-assisted laser desorption/ionization mass spectrometric (MALDI-MS) imaging and Raman microspectroscopic imaging for tissue based studies. The computational workflow can be used to confirm a spectral histopathology (SHP) based on one technique with another technique. In this contribution, we confirmed a Raman spectroscopic based SHP with MALDI-imaging. Owing to this combination, we could demonstrate, for a larynx carcinoma sample, that tissue types and different metabolic states could be extracted from the Raman spectra. Further investigations with the help of MALDI spectra yield a better characterization of variable epithelial differentiation and a better understanding of ongoing dysplastic alterations.


Emigration of neuroepithelial cells from the hindbrain neural tube in the chick embryo.
It is generally believed that after the emigration of neural crest, the neuroepithelial cells of the neural tube are committed to differentiate only as neurons and supporting cells of the central nervous system. Neural crest cells arise from the dorsal portion of the developing neural tube and contribute to the formation of the peripheral nervous system and a variety of non-neural structures. In contrast to this view we have recently shown, by focal application of the vital dye Dil in duck embryos, that an additional population of cells emigrates from the neural tube. By using an entirely different technique we confirm and extend these observations in the chick embryo. Replication-deficient retroviral vector LZ12 containing the gene LacZ was utilized to label the neural tube cells. The viral concentrate was microinjected into the lumen of the rostral hind-brain neural tube, considerably after the completion of emigration of neural crest cells. The labeled cells were monitored in whole mounts and histological sections. Initially, the labeled cells were restricted to the neuroepithelium of the hindbrain neural tube. Subsequently, they were seen in the neural tube and in the ganglion of the fifth cranial nerve (trigeminal ganglion). Later, they migrated beyond the trigeminal ganglion, i.e., into the mesenchyme of the first pharyngeal arch. Immunostaining with the neural crest cell marker, HNK-1, indicated that the emigrated neuroepithelial cells were HNK-1 negative. It is concluded that in the chick embryo some neuroepithelial cells emigrate at the site of attachment of the trigeminal nerve, migrate into the ganglion and then into the mesenchyme of the first arch. This cell population differs antigenically from the neural crest cells.


Serum anticholinergicity is associated with reduced prefrontal brain function in early course schizophrenia.
Increased anticholinergic activity resulting from pharmacotherapies used to treat schizophrenia is associated with poorer cognition. However the neural mechanisms underlying this effect are unknown. In this study of 39 early course schizophrenia outpatients, we demonstrate that increased serum anticholinergic activity is associated with reduced activation across the prefrontal cortex, including the dorsolateral, anterior, and medial prefrontal cortices, during two tasks of cognitive control. Lower activation in the dorsolateral and anterior prefrontal cortices mediated the association between increased anticholinergicity and poorer neurocognitive function. Such findings provide preliminary insight into how anticholinergic medications may impact cognition through reduced prefrontal cortical function in schizophrenia.


1H nuclear-magnetic-resonance studies of the three-dimensional structure of the cardiotoxin CTXIIb from Naja mossambica mossambica in aqueous solution and comparison with the crystal structures of homologous toxins.
Using the previously reported sequence-specific 1H-NMR assignments, structural constraints for the cardiotoxin CTXIIb from Naja mossambica mossambica were collected. These include distance constraints from nuclear Overhauser enhancement measurements both in the laboratory and in the rotating frame, dihedral angle constraints derived from spin-spin coupling constants, and constraints from hydrogen bonds and disulfide bridges. Structure calculations with the distance geometry program DISMAN confirmed the presence of the previously identified antiparallel beta-sheets formed by residues 1-5 and 10-14, and by 20-27, 35-39 and 49-55, and established the nature of the connections between the individual beta-strands. These include a right-handed crossover between the two peripheral strands in the triple-stranded beta-sheet, and a type I tight turn immediately preceding the beta-strand 49-55. The spatial arrangement of the polypeptide backbone in the solution structure of CTXIIb is closely similar to that in the crystal structure of the homologous cardiotoxin VII4 from the same species. In an Appendix the origin of the large pH dependence of two amide proton chemical shifts in CTXIIb is explained.


Advanced design techniques in passive and active tubular solar stills: a review.
Clean water production using green energy supply plays a significant role in the globe's health and economic development. In recent years, so much importance is given on developing the advanced designs of solar stills to improvise the productivity of conventional solar stills. Tubular solar stills (TSSs) are one of the emerging areas to improve clean water productivity. This paper's main aim is detailed review of passive and active tubular solar still design specifications and highlighting the specific merit of each design. The common tube materials in passive and active TSS are glass, stainless Steel 304, vinyl chloride, flexi glass, poly carbonate, and poly ethylene with variation in thickness from 0.07 to 2.5 mm. Diameter of the tube varied from 50 to 280 mm in both the cases. Also, the monetary analysis of TSS is discussed, and the average price of water for passive and active tubular solar still is $0.022 and $0.027 per liter of water. Future perspectives also included in the conclusion section for the possible design and material improvements one can do to enhance the performance of the TSS for the benefit of researches. The excellent cover material for TSS is polythene film when compared to the vinyl chloride sheet. TSS with PCM, wick materials, and corrugated absorber enhance productivity during night time. Multi-effect tubular stills performed 28.70% better in comparison to single-effect stills, and TSSs with horizontal axis are 19.12% more productive than vertical axis tubular stills.


Effect of antibiotic treatment delay on therapeutic outcome of experimental acute otitis media caused by Streptococcus pneumoniae strains with different susceptibilities to amoxicillin.
The effect of delayed administration of amoxicillin on the course of acute otitis media (AOM) caused by two Streptococcus pneumoniae strains with different susceptibilities to amoxicillin (MICs of 0.016 and 1 microg/ml for strains A and B, respectively) was evaluated in the gerbil model. The organisms were inoculated by transbullar challenge into the middle ear, and antibiotic treatment was administered at various times thereafter. The bacteriological and clinical efficacies of treatment diminished significantly with the delay of antibiotic administration. The bacterial eradication rates when antibiotic treatment was started at 2, 5, 8, 18, and 21 h post-bacterial inoculation were different for both strains (95, 95, 90, 55, and 55% for strain A and 95, 95, 65, 10, and 0% for strain B). Results of further experiments using strain B with higher antibiotic doses and numbers of administrations and different follow-up times indicate that the failures observed with the delayed administration were not related to the bacterial burden, selection of antibiotic-resistant mutants, or inadequate pharmacodynamic parameters. Such failures may be related to the metabolic bacterial status. The delayed amoxicillin treatment of AOM caused by S. pneumoniae may lead to therapeutic failures, mainly when organisms with diminished antibiotic susceptibility are involved.


Successful resection of ampullary carcinoma in a father and adenoma in a daughter with familial adenomatous polyposis following detection by surveillance: report of two cases.
This report describes the successful resection of ampullary carcinoma in a 58-year-old man and an adenoma in his 28-year-old daughter after they had undergone proctocolectomy for familial adenomatous polyposis (FAP). Both patients had been monitored by surveillance endoscopy once a year since their proctocolectomy. The father was found to have an ampullary adenoma 26 years after proctocolectomy, and ampullary carcinoma was detected 2 years later, for which pancreatoduodenectomy was performed. Histological examination of the specimen revealed an ampullary carcinoma, 2.5 x 1.7 cm, that had invaded the submucosal layer, but no lymph node metastasis was found. The patient's daughter underwent endoscopy, which showed an ampullary polyp 6 years after total colectomy. Endoscopic mucosal resection of the periampullary lesion was performed, and histological examination revealed a dysplastic tubular adenoma 0.6 x 0.4 cm in diameter. This report reinforces the importance of long-term periodic surveillance of patients with FAP by gastroduodenal endoscopy.


Diagnosing the SAPHO syndrome: a report of three cases and review of literature.
SAPHO, an acronym for synovitis, acne, pustulosis, hyperostosis and osteitis, is a heterogeneous entity with myriad presentations and features overlapping with other entities. It is a differential in patients presenting with skin and bone symptoms, either singly or in combination. Often misdiagnosed radiologically as a malignancy or infection, the diagnosis is seldom thought of. We present three cases referred to us for evaluation of findings unrelated to the presenting symptoms. After evaluation, a (99)Tc bone scan was ordered, which showed the 'bull's head sign' in all the three cases, confirming the diagnosis. We review the literature for SAPHO. It has a few features which point to its diagnosis and can help us to distinguish it from other seronegative arthritis. The clinician should be aware of this entity and should not hesitate to order a (99)Tc bone scan. We conclude that SAPHO is not rare, but rather, it is underdiagnosed. High index of suspicion is necessary for diagnosis. A (99)Tc bone scan is diagnostic and should be ordered in patients having any of the presenting features of the syndrome. We put forward the suggestion of using (99)Tc bone scintigraphy to define a 'pre-MRI' stage of ankylosing spondylitis.


Temperature changes in rheumatoid hand treated with nitrogen vapors and cold air.
The aim of the study was the thermovisual comparison of mean temperature of hand surface changes after local cryotherapy with vapors of nitrogen (-160°C) and cold air (-30°C). Forty-seven patients with rheumatoid arthritis (39 women and 8 men; average age 56.2 ± 10.5 years) were included in the study. They had the application of topic cryotherapy using nitrogen vapors or cold air on one hand. Main outcome measure was surface temperature of dorsal sides of the cooled and contralateral hands. Thermal images of both hands were taken before and up to 3 h after the treatment. One minute after application, nitrogen vapors induced decrease in surface skin temperature of the cooled hand from 28.9 ± 1.8°C to 17.9 ± 2.2°C, P < 0.05, whereas cold air from 29.4 ± 2.4°C to 23.1 ± 2.2°C, P < 0.05. However, significantly lower temperature was obtained with vapors of nitrogen (P < 0.05). Just after the treatment, a rapid rewarming occurred and hands reached baseline temperature in 15 min in both applications and they did not differ till the end of the procedure. Both nitrogen vapors and cold air induce similar temperature changes in hands with the exclusion of temperature obtained 1 min after the treatment. Changes in non-cooled hands indicate contralateral reaction.


Comparison of the antimicrobial activity of propolis extracts obtained by means of various extraction methods.
The objective of the study was to compare the antimicrobial activities of ethanolic propolis extracts obtained using different extraction methods. Extraction of propolis was carried out using 70% ethanol, propolis to ethanol ratios of 1:10 and 1:5, extraction times of 1 or 7 days, and shaking extraction (SE), ultrasound-assisted extraction (UAE), and ultrasound-assisted shaking extraction (SUAE) methods. A total of 12 propolis extract lyophilizates were obtained. Samples were tested for extraction yield and for total phenol content by the Folin-Ciocalteau colourimetric method, and total flavonoid content using a spectrophotometric method. GLC/MS was used for the identification of chemical compounds in selected extract lyophilizates. Antimicrobial activity against selected bacterial and fungal species was assessed using the disk diffusion method. Propolis extracts obtained as the result of 1-day and 7-day shaking extraction followed by 20 min of ultrasound-assisted extraction (SUAE) had better antimicrobial properties as compared to those obtained by SE or UAE alone. SE and UAE gave lower extraction yields as well as lower phenol and flavonoid contents compared to SUAE. No differences were observed with regard to the qualitative composition of extracts obtained by any of the methods. It is best to obtain the extract using the combined method of 1-day extraction and 20-min sonication.


Cloning, sequencing and expression of a full-length rabbit fast skeletal troponin-C cDNA.
A full-length cDNA coding for troponin-C isolated from an adult rabbit fast skeletal muscle library has been sequenced and expressed in an E. coli host. The amino acid sequence derived from the coding region agrees with the published protein sequence except that the first two residues are reversed. The expressed protein was found to be identical to purified rabbit skeletal troponin-C based on electrophoretic mobilities in polyacrylamide gels containing either SDS or urea, and on immunoblotting. These results establish that our troponin-C cDNA clone is suitable for site-directed mutagenesis studies on the structure and function of troponin-C.


A Novel Limb Salvage Technique of External Fixation Protection of Lower Extremity Plastic Reconstructions with Immediate Postoperative Ambulation (Bibbo Flap and Frame Technique).
Non-weight bearing is mandatory after soft tissue reconstructions of the weight-bearing and the high-pressure areas in the lower extremity. The most common method of patient mobilization after surgical reconstruction of chronic foot and ankle wounds has been to place patients non-weight bearing with crutches, walkers, or a wheelchair. Often patients are older, have more complex medical comorbidities, are deconditioned, and simply cannot comply with the prescribed weight-bearing status with these methods, which leads to deconditioning, depression, or noncompliance. Noncompliance quickly leads to failure of the reconstructive effort and the serious threat of limb loss.


Stroller safety.
To assess the incidence and type of stroller injuries in South Australia and factors contributing to their occurrence. Retrospective review of South Australian Health Commission Injury Surveillance data for Adelaide Children's Hospital, Modbury Hospital and Queen Elizabeth Hospital (1986-1992); a prospective survey of 150 stroller users in three metropolitan shopping malls; and testing of backward tipping using loads determined by the AS/NZS 2088 standard. One hundred and forty-nine attendances for unintentional injury resulted from infants either falling out of strollers and prams, or from entrapment of digits in strollers. Eleven infants (7.4%) required admission. One hundred and five injuries (70%) occurred between nine and 15 months of age. Eighty-nine (60%) involved either head/facial/dental injuries or concussion. The survey showed that only 14 strollers (9%) were used correctly (children appropriately harnessed and no shopping on the handles). Five strollers tipped over while carrying an 8 kg load when a 5 kg weighted shopping bag was placed on their handles. One stroller tipped over when a weight of 2 kg was applied at the handle on a 12 degree ramp with an 8 kg load. Only 11 of the 23 strollers commercially available in Adelaide in October 1992 carried the non-mandatory stroller standard. Stroller accidents are a common source of injury and usually result from incorrect use. The stroller standard should be made mandatory and revised to include a shoulder harness, lower the centre of gravity and provide shopping storage.


Aging-associated modulation in the expression of Pax6 in mouse brain.
Symptoms like mental retardation, depression, and anxiety have been observed during aging. Almost similar phenotypes have been evident in patients having haploinsufficiency or mutations in Pax6, a transcriptional regulator. Since Pax6 regulates axon guidance, differentiation of neurons from glia, and neuronal migration, it has been considered as a marker of newly generated neurons. The immunohistochemical analysis of Pax6 positive cells and expression pattern of Pax6 in olfactory lobe, hippocampus, and cerebellum of aging mouse brain have been investigated. The number of Pax6 positive cells and level of Pax6 were reduced progressively in olfactory lobe, cerebellum, and hippocampus from postnatal day-zero (P0) to old age mice. Pax6 positive cells were significantly lower in dentate gyrus, CA1, CA2, and CA3 regions of hippocampus, in mitral cell (MiCe), and internal plexiform (InPl) layers of olfactory lobe, and in granular cell (GrLa), and Purkinje's cell (PuCe) layers of cerebellum from P0 to old age. Thus, modulation in the expression of Pax6 and reduction in Pax6 positive cells show direct association of Pax6 with aging-related neuronal dystrophy.


Coronavirus disease 2019 (COVID-19) vaccine intentions and uptake in a tertiary-care healthcare system: A longitudinal study.
Healthcare workers (HCWs) are a high-priority group for coronavirus disease 2019 (COVID-19) vaccination and serve as sources for public information. In this analysis, we assessed vaccine intentions, factors associated with intentions, and change in uptake over time in HCWs. A prospective cohort study of COVID-19 seroprevalence was conducted with HCWs in a large healthcare system in the Chicago area. Participants completed surveys from November 25, 2020, to January 9, 2021, and from April 24 to July 12, 2021, on COVID-19 exposures, diagnosis and symptoms, demographics, and vaccination status. Of 4,180 HCWs who responded to a survey, 77.1% indicated that they intended to get the vaccine. In this group, 23.2% had already received at least 1 dose of the vaccine, 17.4% were unsure, and 5.5% reported that they would not get the vaccine. Factors associated with intention or vaccination were being exposed to clinical procedures (vs no procedures: adjusted odds ratio [AOR], 1.39; 95% confidence interval [CI], 1.16-1.65) and having a negative serology test for COVID-19 (vs no test: AOR, 1.46; 95% CI, 1.24-1.73). Nurses (vs physicians: AOR, 0.24; 95% CI, 0.17-0.33), non-Hispanic Black (vs Asians: AOR, 0.35; 95% CI, 0.21-0.59), and women (vs men: AOR, 0.38; 95% CI, 0.30-0.50) had lower odds of intention to get vaccinated. By 6-months follow-up, >90% of those who had previously been unsure were vaccinated, whereas 59.7% of those who previously reported no intention of getting vaccinated, were vaccinated. COVID-19 vaccination in HCWs was high, but variability in vaccination intention exists. Targeted messaging coupled with vaccine mandates can support uptake.


Blood biomarkers of traumatic brain injury and cognitive impairment in older veterans.
To determine whether blood-based biomarkers can differentiate older veterans with and without traumatic brain injury (TBI) and cognitive impairment (CogI). We enrolled 155 veterans from 2 veterans' retirement homes: 90 without TBI and 65 with TBI history. Participants were further separated into CogI groups: controls (no TBI, no CogI), n = 60; no TBI with CogI, n = 30; TBI without CogI, n = 30; and TBI with CogI, n = 35. TBI was determined by the Ohio State University TBI Identification Method. CogI was defined as impaired cognitive testing, dementia diagnosis, or use of dementia medication. Blood specimens were enriched for CNS-derived exosomes. Proteins (neurofilament light [NfL], total tau, glial fibrillary acidic protein [GFAP], α-synuclein, β-amyloid 42 [Aβ42], and phosphorylated tau [p-tau]) and cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and interleukin-10) were measured using ultrasensitive immunoassays. Veterans were, on average, 79 years old. In participants with TBI history, 65% had mild TBI; average time from most recent TBI was 37 years. In adjusted analyses, the TBI and CogI groups differed on CNS-enriched exosome concentration of p-tau, NfL, IL-6, TNF-α (all p < 0.05), and GFAP (p = 0.06), but not on Aβ42 or other markers. Adjusted area under the curve (AUC) analyses found that all significantly associated biomarkers combined separated TBI with/without CogI (AUC, 0.85; 95% confidence interval [CI], 0.74-0.95) and CogI with/without TBI (AUC, 0.88; 95% CI, 0.77-0.99). Increased levels of blood-based, CNS-enriched exosomal biomarkers associated with TBI and CogI can be detected even decades after TBI. This study provides Class II evidence that in veterans with a history of TBI, CNS-enriched exosome concentration of p-tau, NfL, IL-6, and TNF-α are associated with CogI.


Publisher Correction: Occurrence and genetic diversity of CRESS DNA viruses in wild birds: a Hungarian study.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with non-alcoholic fatty liver disease.
Liver biopsy is the only reliable way of diagnosing and staging NASH but its invasive nature limits its use. Plasma caspase-generated cytokeratin-18 fragments (CK-18) have been proposed as a non-invasive alternative. We studied its clinical value in a large multiethnic NAFLD population and examined its relationship to clinical/metabolic/histological parameters. 424 middle-aged subjects in whom we measured adipose tissue, liver and muscle insulin resistance (IR), liver fat by MRS (n=275) and histology (n=318). Median CK-18 were elevated in patients with vs. without NAFLD by MRS (209 [IQR: 137-329] vs. 122 [IQR: 98-155]U/L) or with vs. without NASH (232 [IQR: 151-387] vs. 170 [IQR: 135-234]U/L, both p<0.001). Plasma CK-18 raised significantly with any increase in steatosis, inflammation and fibrosis, but there was a significant overlap across disease severity. The CK-18 AUROC to predict NAFLD, NASH or fibrosis were 0.77 (95% CI=0.71-0.84), 0.65 (95% CI=0.59-0.71) and 0.68 (95% CI=0.61-0.75), respectively. The overall sensitivity/specificity for NAFLD, NASH and fibrosis were 63% (57-70%)/83% (69-92%), 58% (51-65%)/68% (59-76%) and 54% (44-63%)/85% (75-92%), respectively. CK-18 correlated most strongly with ALT (r=0.57, p<0.0001) and adipose tissue IR (insulin-suppression of FFA: r=-0.43; p<0.001), less with steatosis, lobular inflammation and fibrosis (r=0.28-0.34, all p<0.001), but not with ballooning, BMI, metabolic syndrome or T2DM. Plasma CK-18 has a high specificity for NAFLD and fibrosis, but its limited sensitivity makes it inadequate as a screening test for staging NASH. Whether combined as a diagnostic panel with other biomarkers or clinical/laboratory tests may prove useful requires further study.


Temporomandibular joint dysplasia and open-mouth jaw locking in the dog.
In 2 Basset Hounds, the condyloid processes of the mandible became subluxated when the mouth was opened widely, resulting in repeated episodes of locking of the coronoid process lateral to the zygomatic arch. Locking was prevented by osteotomy of a ventral portion of the zygomatic arch.


Total chemical synthesis and high-resolution crystal structure of the potent anti-HIV protein AOP-RANTES.
RANTES is a CC-type chemokine protein that acts as a chemoattractant for several kinds of leukocytes, playing an important pro-inflammatory role. Entry of human immunodeficiency virus-1 (HIV-1) into cells depends on the chemokine receptor CCR5. RANTES binds CCR5 and inhibits HIV-1 entry into peripheral blood cells. Interaction with chemokine receptors involves a distinct set of residues at the amino terminus of RANTES. This finding was utilized in the development of a chemically modified aminooxypentane derivative of RANTES, AOP-RANTES, that was originally produced from the recombinant protein using semisynthetic methods. AOP-RANTES has been produced by a novel total chemical synthesis that provides efficient, direct access to large amounts of this anti-HIV protein analog. The crystal structure of chemically synthesized AOP-RANTES has been solved and refined at 1.6 A resolution. The protein is a dimer, with the amino-terminal pentane oxime moiety clearly defined. Total chemical synthesis of AOP-RANTES provides a convenient method of producing the multi-milligram quantities of this protein needed to investigate the molecular basis of receptor binding and antiviral activity. This work provides the first truly high-resolution structure of a RANTES protein, although the structure of RANTES was known from previous nuclear magnetic resonance (NMR) determinations.


Febrigenic signaling to the brain does not involve nitric oxide.
1. The involvement of peripheral nitric oxide (NO) in febrigenic signaling to the brain has been proposed because peripherally administered NO synthase (NOS) inhibitors attenuate lipopolysaccharide (LPS)-induced fever in rodents. However, how the unstable molecule of NO can reach the brain to trigger fever is unclear. It is also unclear whether NOS inhibitors attenuate fever by blocking febrigenic signaling or, alternatively, by suppressing thermogenesis in brown fat. 2. Male Wistar rats were chronically implanted with jugular catheters; their colonic and tail skin temperatures (T(c) and T(sk)) were monitored. 3. Study 1 was designed to determine whether the relatively stable, physiologically relevant forms of NO, that is, S-nitrosoalbumin (SNA) and S-nitrosoglutathione (SNG), are pyrogenic and whether they enhance LPS fever. At a neutral ambient temperature (T(a)) of 31 degrees C, afebrile or LPS (1 microg kg(-1), i.v.)-treated rats were infused i.v. with SNA (0.34 or 4.1 micromol kg(-1); the controls received NaNO(2) and albumin) or SNG (10 or 60 micromol kg(-1); the controls received glutathione). T(c) of SNA- or SNG-treated rats never exceeded that of the controls. 4. In Study 2, we tested whether the known fever-attenuating effect of the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) at a subneutral T(a) (when fever is brought about by thermogenesis) also occurs at a neutral T(a) (when fever is brought about by skin vasoconstriction). At a subneutral T(a) of 24 degrees C, L-NAME (2.5 mg kg(-1), i.v.) attenuated LPS (10 microg kg(-1), i.v.) fever, presumably by inhibiting thermogenesis. At 31 degrees C, L-NAME enhanced LPS fever by augmenting skin vasoconstriction (T(sk) fall). 5. In summary, both SNA and SNG had no pyrogenic effect of their own and failed to enhance LPS fever; peripheral L-NAME attenuated only fever brought about by increased thermogenesis. It is concluded that NO is uninvolved in febrigenic signaling to the brain.


Improving the therapeutic index of topical phenylephrine by reducing drop volume.
This study examined the effect of reducing eyedrop volume on the efficacy and systemic absorption of a given quantity of phenylephrine hydrochloride. Aqueous phenylephrine hydrochloride (2.5%) given in the commercially available drop volume of 32 microliters was compared with 10% aqueous phenylephrine given in an 8-microliters volume. Both preparations contained the same total amount of phenylephrine per drop. Ten subjects had both eyes dilated with each of the phenylephrine solutions according to a randomized, double-crossover sequence. The mean final pupillary diameter was nearly 1.0 mm larger for the 8-microliters drop (P = 0.0033). Nine of ten subjects achieved a larger pupillary diameter with the 8-microliters drop. Systemic absorption, as measured by plasma phenylephrine level, was similar for the two drop volumes. Thus, the 8-microliters drop achieved a significantly larger pupillary dilation without an increase in systemic absorption. Phenylephrine may have the most favorable risk-benefit ratio when administered as a high concentration in a small volume.


Genomic and evolutionary inferences between American and global strains of porcine epidemic diarrhea virus.
Porcine epidemic diarrhea virus (PEDV) has caused severe economic losses both recently in the United States (US) and historically throughout Europe and Asia. Traditionally, analysis of the spike gene has been used to determine phylogenetic relationships between PEDV strains. We determined the complete genomes of 93 PEDV field samples from US swine and analyzed the data in conjunction with complete genome sequences available from GenBank (n=126) to determine the most variable genomic areas. Our results indicate high levels of variation within the ORF1 and spike regions while the C-terminal domains of structural genes were highly conserved. Analysis of the Receptor Binding Domains in the spike gene revealed a limited number of amino acid substitutions in US strains compared to Asian strains. Phylogenetic analysis of the complete genome sequence data revealed high rates of recombination, resulting in differing evolutionary patterns in phylogenies inferred for the spike region versus whole genomes. These finding suggest that significant genetic events outside of the spike region have contributed to the evolution of PEDV.


Chromogranin A and derived peptides in health and disease.
Chromogranin A (CgA) is a member of the granins, a family of acidic proteins found in abundance in (neuro)endocrine cells (e.g., in chromaffin cells) and in some tumors. Like other granins, CgA has a granulogenic role in secretory granule biogenesis and is stored in these organelles. CgA is partially processed differentially in various cell types to yield biologically active peptides, such as vasostatin, pancreastatin, catestatin, and serpinins. In this review, we describe the roles of CgA and several of its derived peptides. CgA, which is elevated in the blood of cancer patients, inhibits angiogenesis and exerts protective effects on the endothelial barrier function in tumors, thus affecting response to chemotherapy. Recent studies indicate that the serpinins promote cell survival and myocardial contractility and relaxation. Other peptides such as pancreastatin were found to have significant effects on inhibition of glucose-stimulated insulin secretion and glucose up-take, induction of glycogenolysis in hepatocytes, and inhibition of lipogenesis. In contrast, catestatin has opposite effects to that of pancreastatin in glucose metabolism and lipogenesis. Catestatin appears to also play a significant role in cardiac function, blood pressure regulation, and mutations in the catestatin domain of the CgA gene are associated with hypertension in humans.


Changes in myocardial ischaemia during isosorbide dinitrate or indoramin therapy in patients with stable angina using relations between the ST segment and heart rate.
The effect of isosorbide dinitrate or indoramin on myocardial ischaemia was examined in patients with stable angina pectoris. In a prospective trial, randomization resulted in 8 and 9 patients, respectively, given isosorbide dinitrate in a dose of 30-90 mg daily, and indoramin in a dose of 75-225 mg daily; 2 of these patients were serially examined during the two types of therapy. Changes in myocardial ischaemia were assessed by exercise testing using 12 standard electrocardiographic leads and a bipolar lead CM5. Individual and group comparisons showed that isosorbide dinitrate resulted in an increase in ST segment depression, the maximal ST/heart rate slope and the ratio of net ST segment depression to increases in heart rate (at least P less than 0.01). In contrast, with indoramin therapy there were no significant changes in these indices. The results in these patients suggest that isosorbide dinitrate leads more consistently to increases in the severity of myocardial ischaemia than indoramin, although this effect on ischaemia is apparently less than the benefit of these agents on exercise performance.


Ileal intubation is not associated with higher detection rate of right-sided conventional adenomas and serrated polyps compared to cecal intubation after adjustment for overall adenoma detection rate.
High cecal intubation rate (CIR) is associated with significant improved adenoma detection rate (ADR), however, self-reported CIR may be overestimated and inadequate documentation of cecal intubation is associated with a lower polyp detection rate compared to clear documentation. We aimed to investigate if ileal intubation may be associated with higher detection rates (DR) for right-sided conventional adenomas (cAD) and serrated polyps (SP) compared to cecal intubation in a large screening colonoscopy cohort. Retrospective analysis of individuals ≥50 years with average risk for colorectal cancer (CRC) who underwent screening colonoscopy between 01/01/2012 and 14/12/2016 at a tertiary academic hospital and six community-based private practices. Exclusion criteria were conditions with increased risk for CRC (e.g. inflammatory bowel disease, history of CRC, hereditary cancer syndromes), previous colonoscopy at the same institution, and incomplete procedures. Right-sided colon was defined as caecum and ascending colon. 4.138 individuals were analysed (mean age 62 years, 52.1% female). DR for right-sided cADs and SPs were significantly higher after ileal compared to cecal intubation in univariate (12.5% vs. 6.8%, p < 0.001, and 6.3% vs. 3.3%, p < 0.001), but not in multivariate analysis (OR 1.025, 95%-CI 0.639-1.646, p = 0.918, and OR 0.937, 95%-CI 0.671-1.309, p = 0.704). DRs did not differ between ileal and cecal intubation for endoscopists with ADR ≥25 and < 25%, respectively. ADR ≥25% was significantly associated with ileal intubation (OR 21.862, 95%-CI 18.049-26.481, p < 0.001). Ileal intubation may not provide any benefit over cecal intubation concerning the detection of cADs and SPs in the right-sided colon.


Causal analysis of academic performance.
Maximum likelihood methods are presented to test for the relations between causes and effects in linear path diagrams, without assuming that estimates of causes are free of error. Causal analysis is illustrated by published data of the Equal Educational Opportunity Survey, which show that American schools do not significantly modify socioeconomic differences in academic performance and that little of the observed racial difference in academic performance is causal. For two races differing by 15 IQ points, the differential if social class were randomized would be only about 3 points. The principle is stressed that a racial effect in a causal system may be environmental and that its etiology can be studied only by analysis of family resemblance in hybrid populations.


Effect of replacing the primary quinone by different species on the ultrafast photosynthetic electron transfer in bacterial reaction centres.
Using picosecond absorption spectroscopy it has been shown that in Rhodobacter sphaeroides reaction centres the substitution of the primary quinone acceptor (QA), ubiquinone-10, by other quinone species (with redox potentials higher or lower than that of ubiquinone-10) has essentially no modifying effect on the reaction centre protein. The molecular relaxation processes that accompany the localization and stabilization of a photo-excited electron on the intermediate acceptor, bacteriopheophytin (I), are not affected, although the subsequent transfer of the electron from I to QA is slowed down. Consequently, this leads to a lower quantum efficiency of high rate of direct I-----QA reaction is normally due to the specificity of the primary quinone species and its binding site in the reaction centre protein which provide optimum steric and chemical conditions for an effective interaction between I and QA.


TrueFisp versus HASTE sequences in 3T cine MRI: Evaluation of image quality during phonation in patients with velopharyngeal insufficiency.
To evaluate the image quality of two fast dynamic magnetic resonance imaging (MRI) sequences: True fast imaging with steady state precession (TrueFisp) was compared with half-Fourier acquired single turbo-spin-echo (HASTE) sequence for the characterization of velopharyngeal insufficiency (VPI) in repaired cleft palate patients. Twenty-two patients (10 female and 12 male; mean age, 17.7 ± 10.6 years; range, 9-31) with suspected VPI underwent 3-T MRI using TrueFisp and HASTE sequences. Imaging was performed in the sagittal plane at rest and during phonation of "ee" and "k" to assess the velum, tongue, posterior pharyngeal wall and a potential VP closure. The results were analysed independently by one radiologist and one orthodontist. HASTE performed better than TrueFisp for all evaluated items, except the tongue evaluation by the orthodontist during phonation of "k" and "ee". A statistically significant difference in favour of HASTE was observed in assessing the velum at rest and during phonation of "k" and "ee", and also in assessing VP closure in both raters (p < 0.05). TrueFisp imaging was twice as fast as HASTE (0.36 vs. 0.75 s/image). Dynamic HASTE images were of superior quality to those obtained with TrueFisp, although TrueFisp imaging was twice as fast. • Dynamic MRI is an invaluable tool for diagnosing VPI. • Dynamic HASTE images were of superior quality to those obtained with TrueFisp. • TrueFisp imaging was twice as fast as HASTE imaging.


Transforming growth factor-β1 decreases erythropoietin production through repressing hypoxia-inducible factor 2α in erythropoietin-producing cells.
Renal erythropoietin (EPO)-producing (REP) cells produce EPO through hypoxia-inducible factor (HIF) 2α-activated gene transcription. Insufficient EPO production leads to anemia in patients with chronic kidney disease. Although recombinant EPO is effective to improve anemia, no reliable REP cell lines limit further progress of research and development of novel treatment. We screened Epo mRNA expression in mouse fibroblast cell lines. Small interfering RNA specific for HIF1α or HIF2α was transfected to study Epo expression in C3H10T1/2 cells. The effect of transforming growth factor-β1 (TGF-β1) on HIF-EPO axis was studied in C3H10T1/2 cells and mice. Similar to mouse REP pericytes, C3H10T1/2 cells differentiated to α-smooth muscle actin+ myofibroblasts after exposure to TGF-β1. Specific HIF knockdown demonstrated the role of HIF2α in hypoxia-induced Epo expression. Sustained TGF-β1 exposure increased neither DNA methyltransferase nor methylation of Epas1 and Epo genes. However, TGF-β1 repressed HIF2α-encoding Epas1 promptly through activating activin receptor-like kinase-5 (ALK5), thereby decreasing Epo induction by hypoxia and prolyl hydroxylase domain inhibitor roxadustat. In mice with pro-fibrotic injury induced by ureteral obstruction, upregulation of Tgfb1 was accompanied with downregulation of Epas1 and Epo in injured kidneys and myofibroblasts, which were reversed by ALK5 inhibitor SB431542. C3H10T1/2 cells possessed the property of HIF2α-dependent Epo expression in REP pericytes. TGF-β1 induced not only the transition to myofibroblasts but also a repressive effect on Epas1-Epo axis in C3H10T1/2 cells. The repressive effect of TGF-β1 on Epas1-Epo axis was confirmed in REP pericytes in vivo. Inhibition of TGF-β1-ALK5 signaling might provide a novel treatment to rescue EPO expression in REP pericytes of injured kidney.


Recovery of metagenome-assembled genomes from the phyllosphere of 110 rice genotypes.
The plant microbiota plays crucial roles in sustaining plant health and productivity. Advancing plant microbiome research and designing sustainable practices for agriculture requires in-depth assessments of microorganisms associated with different host plants; however, there is little information on functional aspects of many microorganisms of interest. Therefore, we enriched microorganisms from the phyllosphere of 110 rice genotypes and subjected them to shotgun metagenomic sequencing to reconstruct bacterial genomes from the obtained datasets. The approach yielded a total of 1.34 terabases of shotgun-sequenced metagenomic data. By separately recovering bacterial genomes from each of the 110 rice genotypes, we recovered 569 non-redundant metagenome-assembled genomes (MAGs) with a completeness higher than 50% and contaminations less than 10%. The MAGs were primarily assigned to Alphaproteobacteria, Gammaproteobacteria, and Bacteroidia. The presented data provides an extended basis for microbiome analyses of plant-associated microorganisms. It is complemented by detailed metadata to facilitate implementations in ecological studies, biotechnological mining approaches, and comparative assessments with genomes or MAGs from other studies.


Electro-enhanced phytoremediation system on the removal of trace metal concentration from contaminated water.
The combination of electro-enhanced and hydroponic phytoremediation hereinafter referred to as electro-enhanced phytoremediation (EP) system, has been employed for rapid removal of trace metal concentration of lead (II) from contaminated water using Kentucky bluegrass (Poa pratensis L.) as accumulator plant. In this study, for rapid assessment the effectiveness of two-dimensional (2D) electrode configuration in electro-enhanced system was evaluated by agar media for 48h period of time. Furthermore, these configurations were applied to enhance the EP system for 9d period of time. Also, a common agrochemical-urea as chaotropic agent to facilitate the healthy growth of plant in contaminated water was evaluated. The results showed that the accumulation of lead (II) concentration was higher in the plant roots (i.e. high bioaccumulation coefficient (BC) value) than in aerial parts of plant (i.e. low translocation factor (TF) value). Also, the accumulation of lead (II) concentration in plant was higher under the treated urea of EP system. The chlorophyll content, biomass accumulation productivity, and water content (i.e. dry weight-fresh weight (DW/FW) ratio) of plant either under the treated urea or untreated urea with high accumulation of lead (II) concentration revealed that the Kentucky bluegrass has able to hold out the plant stress.


Retention in Care, Mortality, Loss-to-Follow-Up, and Viral Suppression among Antiretroviral Treatment-Naïve and Experienced Persons Participating in a Nationally Representative HIV Pre-Treatment Drug Resistance Survey in Mexico.
We describe associations of pretreatment drug resistance (PDR) with clinical outcomes such as remaining in care, loss to follow-up (LTFU), viral suppression, and death in Mexico, in real-life clinical settings. We analyzed clinical outcomes after a two-year follow up period in participants of a large 2017-2018 nationally representative PDR survey cross-referenced with information of the national ministry of health HIV database. Participants were stratified according to prior ART exposure and presence of efavirenz/nevirapine PDR. Using a Fine-Gray model, we evaluated virological suppression among resistant patients, in a context of competing risk with lost to follow-up and death. A total of 1823 participants were followed-up by a median of 1.88 years (Interquartile Range (IQR): 1.59-2.02): 20 (1%) were classified as experienced + resistant; 165 (9%) naïve + resistant; 211 (11%) experienced + non-resistant; and 1427 (78%) as naïve + non-resistant. Being ART-experienced was associated with a lower probability of remaining in care (adjusted Hazard Ratio(aHR) = 0.68, 0.53-0.86, for the non-resistant group and aHR = 0.37, 0.17-0.84, for the resistant group, compared to the naïve + non-resistant group). Heterosexual cisgender women compared to men who have sex with men [MSM], had a lower viral suppression (aHR = 0.84, 0.70-1.01, p = 0.06) ART-experienced persons with NNRTI-PDR showed the worst clinical outcomes. This group was enriched with women and persons with lower education and unemployed, which suggests higher levels of social vulnerability.


Preharvest aflatoxin contamination of groundnuts subjected to terminal drought stress in postrainy season.
Groundnuts grown in the postrainy season under terminal drought stress imposed by withholding irrigation, or under a water-deficit gradient created by line-source sprinkler irrigation, were examined for preharvest aflatoxin contamination. High levels of aflatoxin B1 were found in damaged seeds in both situations. When grown under continuous drought-stress, toxin levels in damaged seed samples ranged from 1480 to 2467 [Symbol: see text]g/kg in the 1990/91, and 1.3 to 2000 [Symbol: see text]g/kg in the 1991/92 postrainy seasons. Aflatoxin B1 contamination in all damaged seed samples increased with increasing water deficit; toxin levels ranged from 26 to 850 [Symbol: see text]g/kg across the water deficit gradient. Aflatoxin was either absent or almost negligible (1-2 [Symbol: see text]g/kg) in apparently undamaged seed samples. Low risk of aflatoxin contamination in apparently undamaged seeds of groundnuts grown in postrainy seasons is indicated, even when there is terminal drought stress.


Physostigmine, but not 3,4-diaminopyridine, improves radial maze performance in memory-impaired rats.
The results of some studies suggest that 3,4-diaminopyridine (3,4-DAP), a drug that enhances the release of acetylcholine, may improve memory. The present study examined the ability of 3,4-DAP to reverse the memory impairment produced by scopolamine and the ability of 3,4-DAP and physostigmine to reverse the memory impairment produced by quinolinic acid lesions of the nucleus basalis magnocellularis (nbm) in rats. Mnemonic functioning was assessed with the use of a partially baited eight-arm radial maze. Entries into arms that were never baited were defined as reference memory errors; entries into baited arms from which the food already had been eaten were defined as working memory errors. In Experiment 1, 0.1 mg/kg scopolamine produced a significant increase in working and reference memory errors. Various doses of 3,4-DAP had no significant ameliorative effect on the mnemonic deficit. In Experiment 2, cholinergic function was impaired using a unilateral intra-nbm injection of quinolinic acid (120 nmol in 1.0 microliter). These lesions reduced the levels of the cholinergic marker, choline acetyltransferase, in the cortex by more than 40%. Results showed that the nbm lesion animals were significantly more impaired on the working than reference memory component of the task. Physostigmine (0.01, 0.05, 0.10, 0.20, 0.50 mg/kg) dose-dependently decreased the number of working but not reference memory errors. 3,4-DAP (10(-8), 10(-6), 10(-4), 10(-2), 10(0) mg/kg) had no reliable effect. It was concluded that physostigmine, but not 3,4-DAP, ameliorates memory impairments following decreases in cholinergic function.


Radiation therapy for small-cell lung cancer: results of the 1995-1997 patterns of care process survey in Japan.
The Patterns of Care Study (PCS) conducted a nationwide audit survey in order to establish the national practice process of radiation therapy for small-cell lung cancer (SCLC) and examined the influence of institutional stratification on the process of care in Japan. The PCS randomly sampled institutions and patients using a two-stage cluster method and surveyed the process of radiation therapy for 174 stage I-III SCLC patients according to the category of institution, stratified as follows: A1, academic institutions treating > or = 300 patients a year; A2, <300 patients; B1, non-academic institutions treating > or = 120 patients a year; and B2, <120 patients. Karnofsky performance status distributions showed significant variance by stratification of institutions (P=0.013). Patients treated on an outpatient basis accounted for 32% in A1, 23% in A2, 8% in B1, but only 5% in B2 (P=0.007). A photon energy > or = 10 MV was used for 87% of patients in A1, 69% in A2, 54% in B1 and 23% in B2 (P=0.001). Contralateral hilus was irradiated for 11% of patients in A1, 17% in A2, 29% in B1 and 3% in B2 (P=0.001). Field size reduction during the treatment course was done for 77% of patients in A1, 54% in A2, 60% in B1 and 42% in B2 (P=0.007). Ninety-two percent of patients received combined chemotherapy and radiation therapy, and the most frequently used drugs were etoposide (91%) and cisplatin (69%). The results of clinical studies on SCLC had favorably penetrated into the clinical practice. However, the stratification of institutions significantly affected the process of radiation therapy in Japan.


Induction of heat-shock proteins enhances myocardial and endothelial functional recovery after prolonged cardioplegic arrest.
The aim of this study was to investigate the role of heat-shock proteins after heat-shock stress on the post-ischemic recovery of cardiac mechanical and endothelial function following a prolonged cardiac arrest. Isolated working rat hearts were subjected to a cardioplegic arrest for 4 hours at 4 degrees C. Three groups (n = 8 in each) were studied: (1) control, (2) sham-treated, and (3) heat-shocked rats. Postischemic recovery of cardiac output and endothelial function (as percent of preischemic control values) was 57.8% +/- 2.8% and 20.8% +/- 3.9% in group 1, 50.9% +/- 4.0% and 26.3% +/- 5.9% in group 2, and 74.0% +/- 2.4% and 51.2% +/- 8.0% in group 3, respectively. Both postischemic myocardial and endothelial function were improved by heat stress.


Prevalence of Toxocara spp. eggs in some public grounds and highway rest areas in Kansas.
Out of a total of 282 soil samples obtained from public areas, 58 samples contained Toxocara spp. eggs. This gave an overall prevalence of 20.6%. Highway rest areas were contaminated and childrens sand boxes had the highest percentage of recovery of all.


Psychogenic pain: a study of marital adjustment.
The marital adjustment of patients with psychogenic pain disorder was evaluated and compared with a matched group of patients with other neurotic disorders. Pain patients spouses were found to have better marital adjustment and less psychiatric morbidity than the spouses of neurotic patients. These findings are discussed in terms of the concepts of "sick role homeostasis" and "tertiary gain".


Growth hormone induces transforming growth factor-β1 in podocytes: Implications in podocytopathy and proteinuria.
Pituitary growth hormone (GH) is essential for growth, metabolism, and renal function. Overactive GH signaling is associated with impaired kidney function. Glomerular podocytes, a key kidney cell type, play an indispensable role in the renal filtration and express GH receptors (GHR), suggesting the direct action of GH on these cells. However, the precise mechanism and the downstream signaling events by which GH leads to diabetic nephropathy remain to be elucidated. Here we performed proteome analysis of the condition media from human podocytes and confirmed that GH-induces TGF-β1. Inhibition of GH/GHR stimulated-JAK2 signaling abrogates GH-induced TGF-β1 secretion. Mice administered with GH showed glomerular manifestations concomitant with proteinuria. Pharmacological inhibition of TGF-βR1 in mice prevented GH-induced TGF-β dependent SMAD signaling and proteinuria. Conditional deletion of GHR in podocytes protected mice from streptozotocin-induced diabetic nephropathy. GH and TGF-β1 signaling components expression was elevated in the kidneys of human diabetic nephropathy patients. Our study identifies that GH induces TGF-β1 in podocytes, contributing to diabetic nephropathy.


Effects of glimepiride on insulin secretion and sensitivity in patients with recently diagnosed type 2 diabetes mellitus.
The exact mechanism of the efficacy of glimepiride in the achievement of glycemic control has not yet been clearly defined. This study was conducted to examine the influence of glimepiride on insulin secretion and sensitivity in patients with type 2 diabetes mellitus (DM) of recent onset. This 24-week, open-label, controlled trial was conducted at the Division of Endocrinology and Metabolism, Veterans Affairs Medical Center (Phoenix, Arizona). Study participants were aged 32 to 75 years and had recent-onset (established by a short duration of symptoms 6 weeks to 6 months prior to the study) type 2 DM, or were age-matched healthy volunteers (control group). In the diabetic patients, glimepiride tablets were administered orally, initially at 2 mg once daily in the morning, with the dosage increased by 1 mg every 2 weeks until fasting plasma glucose (FPG) decreased to 6.7 mmol/L; the dosage was then maintained for the remainder of the 24-week study period. Oral glucose tolerance tests (OGTTs) were conducted in the control group and before treatment and at 24 weeks after the achievement and maintenance of glycemic control (glycosylated hemoglobin <7.0%) in the diabetic group. For OGTT, plasma insulin and glucose levels were determined after the subjects fasted overnight and then at every 15 minutes for 2 hours after glucose challenge. Fourteen diabetic men (mean [SEM] age, 50 [6] years; range, 32-75 years) and 10 male healthy controls (mean [SD] age, 48 [5] years; range, 30-68 years) were enrolled. In the DM group, FPG decreased significantly after treatment ( P<0.001); fasting plasma insulin was markedly elevated before treatment (P<0.001 vs controls) and decreased after treatment ( P<0.01) but did not normalize; first-phase insulin secretion was markedly inhibited before treatment ( P<0.001 vs controls) and normalized after treatment ( P<0.001) total insulin secretion significantly improved after treatment ( P<0.01) but did not normalize. Finally, the pretreatment insulin sensitivity index decreased significantly (P<0.01) after treatment and normalized in 6 of 14 patients (42.9%) with type 2 DM. In this study, glimepiride achieved desirable glycemic control in patients with recent-onset type 2 DM through improvement in insulin secretion and sensitivity.


Influence of secondary settling tank performance on suspended solids mass balance in activated sludge systems.
Secondary settling is the final step of the activated sludge-based biological waste water treatment. Secondary settling tanks (SSTs) are therefore an essential unit of producing a clear effluent. A further important function of SSTs is the sufficient thickening to achieve highly concentrated return sludge and biomass within the biological reactor. In addition, the storage of activated sludge is also needed in case of peak flow events (Ekama et al., 1997). Due to the importance of a high SST performance the problem has long been investigated (Larsen, 1977; Krebs, 1991; Takács et al., 1991; Ekama et al., 1997; Freimann, 1999; Patziger et al., 2005; Bürger et al., 2011), however, a lot of questions are still to solve regarding e.g. the geometrical features (inflow, outflow) and operations (return sludge control, scraper mechanism, allowable maximum values of surface overflow rates). In our study we focused on SSTs under dynamic load considering both the overall unsteady behaviour and the features around the peaks, investigating the effect of various sludge return strategies as well as the inlet geometry on SST performance. The main research tool was a FLUENT-based novel mass transport model consisting of two modules, a 2D axisymmetric SST model and a mixed reactor model of the biological reactor (BR). The model was calibrated and verified against detailed measurements of flow and concentration patterns, sludge settling, accompanied with continuous on-line measurement of in- and outflow as well as returned flow rates of total suspended solids (TSS) and water. As to the inlet arrangement a reasonable modification of the geometry could result in the suppression of the large scale flow structures of the sludge-water interface thus providing a significant improvement in the SST performance. Furthermore, a critical value of the overflow rate (q(crit)) was found at which a pronounced large scale circulation pattern develops in the vertical plane, the density current in such a way hitting the outer wall of the SST, turning then to the vertical direction accompanied with significant flow velocities. This phenomenon strengthens with the hydraulic load and can entrain part of the sludge thus resulting in unfavourable turbid effluent. As a representative case study an operating circular SST most commonly used in practice was investigated. Focusing on the sludge return strategies, it was found that up to a threshold peak flow rate the most efficient way is to keep the return sludge flow rate constant, at 0.4Q(MAX). However, once the inflow rate exceeds the threshold value the return sludge flow rate should be slowly increased up to 0.6Q(MAX), performed in a delayed manner, about 20-30 min after the threshold value is exceeded. For preserving the methodology outlined in the present paper, other types of SSTs, however, need further individual investigations.


Prophylactic effect of intravenous tiapamil on methylergometrine-induced coronary artery spasm in patients with variant angina: randomized double-blind trial.
Tiapamil is a new calcium entry blocker. The ability of its intravenous form to prevent methylergometrine-induced coronary artery spasm was studied in 11 consecutive patients with angiographically documented vasospastic angina. The study was designed as a double-blind crossover trial of tiapamil vs placebo. Each patient received, in a randomized order, either tiapamil, as a 1.5 mg/kg intravenous bolus followed by a 50 micrograms/kg/min infusion lasting 3 hours, or a matched placebo. Immediately after the infusion, methylergometrine tests were performed with up to 0.4 mg of methylergometrine or until a positive ECG was recorded. Compared to the values obtained after placebo infusion, tiapamil significantly lowered systolic and diastolic blood pressure (respective pre- and posttiapamil values: 119.9 +/- 17.7 vs 142.1 +/- 25.5 mm Hg, p less than 0.01; and 72.0 +/- 9.1 vs 82.4 +/- 9.3 mm Hg, p less than 0.02); the drug exerted no significant effect on heart rate (63.9 +/- 13.3 vs 67.6 +/- 16.5 bpm, NS), PR interval (0.180 +/- 0.020 vs 0.177 +/- 0.017 sec NS), or QTc interval (404.4 +/- 16.5 vs 396.0 +/- 26.6 msec, NS). After placebo, 10 patients had positive methylergometrine tests following single doses ranging from 0.1 to 0.4 mg. The remaining patient developed ventricular bigeminy, which resolved immediately after administration of isosorbide dinitrate; his test was therefore considered negative in the evaluation of the results. In contrast, after tiapamil, eight patients had negative tests for doses of up to 0.4 mg methylergometrine, and three had positive tests for the same methylergometrine doses as after the placebo.(ABSTRACT TRUNCATED AT 250 WORDS)


Meanwhile back at the ranch: training residents in clinical preventive medicine.
In view of the current growing interest in prevention as an integral part of health care, it is timely to consider clinical preventive medicine (CPM) training approaches that best prepare physicians to deliver appropriate and effective preventive services. During CPM training, skills residents most need to acquire include methods of counseling on health promotion and techniques for advising patients on reducing health risks by changing disease-promoting behavior. University of Arizona residents in the General Preventive Medicine program receive this training focus at Canyon Ranch, a Tucson health resort and university training site. This training is an important component of the CPM area of emphasis in the residency program. Training emphasizes risk reduction and health promotion with a large volume of patients whose aim is to effect lifestyle changes. Emphasis is placed on acquiring skills in clinical prevention. Counseling and patient education are the primary foci. Evaluation data indicate that residents' perception of the rotation's benefit to their education is high, and interest in considering practice in a similar setting is reinforced as a result of the experience. Medical educators in preventive medicine and primary care need to turn their attention to finding appropriate training sites with suitable role models to teach counseling and patient education skills.


A prospective longitudinal study of growth velocity in twin pregnancy.
Fundamental research into the growth of twins is lacking. Twin growth in utero is commonly assumed to follow similar patterns of growth as that of singletons. This preliminary descriptive study on twin pregnancy aimed to define growth velocity as gestation advances, and to study if twin order, fetal sex, zygosity and chorionicity have any relationship to growth velocity. One hundred and sixty-two women with twin pregnancies had an ultrasound examination at fortnightly intervals from 16 weeks until delivery. Fetal measurements of biparietal diameter, abdominal circumference and femur length were performed at each examination. Growth velocity for each parameter was defined as the difference in measurements for that parameter divided by the time interval between measurements. Postnatally, zygosity and chorionicity were determined by genetic fingerprinting and inspection of the placenta, respectively. Growth velocity for all parameters decreased as gestation advanced, with the downward trend more noticeable after 32 weeks. Maximum and minimum growth occurred at 22-23 weeks and 36-37 weeks, respectively. Maximum and minimum growth velocities for the abdominal circumference were 1.7 and 0.8 cm/week, respectively. Birth order, fetal sex, chorionicity and zygosity were not related to growth velocity. These preliminary results suggest that growth velocity in twins decreases after 32 weeks' gestation. It appears that growth velocity is independent of birth order, fetal sex, chorionicity and zygosity.


Rheological properties of composite polymers and hybrid nanocomposites.
This paper summarizes a review of the viscosimetric, viscoelastic and rheological properties of polymers and hybrid nanocomposite polymers. Hybrid nanocomposites can be combined from natural fibers or synthetic fibers and/or both. The hybrid nanocomposite polymer offers the designer the opportunity to achieve the required characteristics to a considerable extent controlled by the choice of appropriate fibers or fillers and the polymer architecture. The rheological behavior of hybrid nanocomposite depends on fiber content, fiber length, fiber orientation, fiber-to-matrix bonding, fiber configuration and filler, respectively. Further, rheological properties of hybrid nanocomposite polymers by introducing various charges were examined discussed.


Studying block in cloned N-methyl-D-aspartate (NMDA) receptors.
The biophysics of block of NMDA receptor channels has been investigated extensively during the past 8 years. In the last few years, cloned NMDA receptor channels have become available. Here we have discussed advantages and disadvantages of studying block phenomena in cloned NMDA receptors. Some recent work on the pore block of the cloned NMDA receptor channels was critically reviewed and extended by data about the calcium block. Novel effects of kainate on cloned NMDA receptors and of NMDA on cloned AMPA receptors were reported and discussed with respect to recent work concerning possible occurrence of NMDA-AMPA hybrid channels.


Structures of intact glycoproteins from vibrational circular dichroism.
Vibrational circular dichroism (VCD) spectra for the glycoproteins alpha1-acid glycoprotein (AGP) and bovine submaxillary mucin (BSM), have been measured in D2O solutions and for the films prepared from aqueous (H2O) buffer solutions in the 1800 to 900 cm(-1) region. The solution VCD results revealed that AGP has beta-sheet structure, along with a significant amount of alpha-helix as evidenced from a W pattern in the amide I region. The VCD of BSM solution suggested a polyproline II type structure, characterized by the appearance of strong negative couplet in the amide I region. The film VCD results on AGP and BSM suggested that the secondary structures of polypeptide fold in the film state are similar to those in the solution. The absence of any significant film VCD in the low frequency region (1200-900 cm(-1)), suggested that the dominant linkage for carbohydrate residues is likely to be a beta linkage. VCD spectroscopy gains importance in the secondary structural analysis of polypeptide fold in glycoproteins due to the absence of interfering VCD from the carbohydrate residues in the conformationally sensitive amide I region. Also, film VCD studies permit measurements in the low wavenumber region (1200-900 cm(-1)) that reveal the dominant type of linkage for carbohydrate residues. Such clear structural information is unlike that from ECD, where ECD bands of acylated amino sugar residues interfere with those of polypeptide backbone in the conformationally sensitive far-UV region.


Synthesis of titanium oxide nanoparticles using Aloe barbadensis mill and evaluation of its antibiofilm potential against Pseudomonas aeruginosa PAO1.
Titanium dioxide nanoparticles (TiO2-NPs) were synthesized using the aqueous leaf extract of Aloe barbadensis as a reducing and fabricating agent. The biosynthesis of the TiO2-NPs was initially confirmed by UV-vis spectroscopy. Based on the HRTEM and FESEM analysis, the biosynthesized NPs were found to be polydispersed and predominantly spherical in shape, with an average size of ~20 nm. A sharp and strong characteristic peaks of titanium (Ti) and oxygen (O) observed in the EDS pattern confirmed the synthesis of the TiO2-NPs. The FTIR spectroscopy suggested the presence of terpenoids, flavonoids and proteins which might be responsible for the biosynthesis and fabrication of the TiO2-NPs. The crystalline nature of the synthesized TiO2-NPs constituting of a mixture of brookite, anatase, and rutile phases was indicated by the XRD pattern. The spectral window around 180-1000 cm-1 covered the high-frequency Raman spectra of the TiO2-NPs. The Raman vibrational spectrum showed four Eg modes centered at 197.84, 399.24, 514.50, and 641.58 cm-1 representing the anatase phase of TiO2-NPs. The strongest and broadened peak of anatase was observed at the frequency of 641.58 cm-1. The metabolic activity of P. aeruginosa exposed to the MIC of TiO2-NPs was measured based on the reduction of tetrazolium salt by the dehydrogenase enzyme, produced by the metabolically active bacterial cells. The reduction in TTC was evident from the appearance of a red colored formazan in the solution. A noticeable suppression in the cell viability by 30.76 ± 3.96% of P. aeruginosa in the biofilm mode was found in presence of TiO2-NPs. Furthermore, the Minimum Inhibitory Concentration (MIC) of TiO2-NPs exhibited profound antibiofilm activity against P. aeruginosa by effectively preventing the adherence of the planktonic cells to the substratum. Thus, these NPs may be employed in controlling bacterial infections associated with biofilm.


Characterization of an ATPase on the inside of rat-liver nuclear envelopes by affinity labeling.
Nuclear envelope membranes from rat liver cells contain ATPases, one of which can be inhibited and irreversibly labeled by (S-dinitrophenyl)-6-mercaptopurine riboside triphosphate. Inhibition and covalent substitution of the ATPase are achieved only after disruption of the nuclei, the ATP analogue is inactive on the ATPase activity of whole nuclei or on vesicles of the membrane prepared after a modified heparin method of Bornens and Courvalin. Electron micrographs and scanning micrographs helped to establish the characterization of closed vesicles and intact nuclei. With the aid of (alpha-32P)-labeled, and of the (beta, gamma-32P)-labeled analogue, it was possible to demonstrate the incorporation of the nucleotide into a few protein regions of the nuclear membrane disc electrophoresis pattern.


Artificial neural network as a classification method of mice by their calls.
Call of animals is one of the main behavioral expressions. It contains important and abundant biological meanings; among these meanings what is most important is that they reveal the characteristics of the animal. Therefore, animals can be classified according to their calls. In this paper we proposed an artificial neural network (ANN) method to classify mice based on their calls. Experiment results show its effectiveness and usefulness.


Development and clinical consequences of white matter lesions in Fabry disease: a systematic review.
Fabry disease (FD) is a rare lysosomal storage disorder that might result in, amongst other complications, early stroke and white matter lesions (WMLs). More insight in WMLs in FD could clarify the role of WMLs in the disease presentation and prognosis in FD. In this systematic review we assessed the prevalence, severity, location and course of WMLs in FD. We also systematically reviewed the evidence on the relation between WMLs, disease characteristics and clinical parameters. We searched Pubmed, EMBASE and CINAHL (inception to Feb 2018) and identified articles reporting on FD and WMLs assessed with MRI. Prevalence and severity were assessed for all patients combined and divided by sex. Out of 904 studies a total of 46 studies were included in the analyses. WMLs were present in 46% of patients with FD (581 out of 1276 patients, corrected mean age: 38.8 years, range 11.8-79.3) and increased with age. A total of 16.4% of patients (31 out of 189 patients, corrected mean age: 41.1 years, range 35.8-43.3 years) showed substantial confluent WMLs. Men and women showed comparable prevalence and severity of WMLs. However, men were significantly younger at time of WML assessment. Patients with classical FD had a higher chance on WMLs compared to non-classical patients. Progression of WMLs was seen in 24.6% of patients (49 out of 199 patients) during 38.1 months follow-up. Progression was seen in both men and women, with and without enzyme replacement therapy, but at an earlier age in men. Stroke seemed to be related to WMLs, but cerebrovascular risk factors, cardiac and renal (dys)function did not. Pathology in the brain in FD seemed to extend beyond the WMLs into the normal appearing white matter. A significant group of FD patients has substantial WMLs and male patients develop WMLs earlier compared to female patients. WMLs could be used in clinical trials to evaluate possible treatment effects on the brain. Future studies should focus on longitudinal follow-up using modern imaging techniques, focusing on the clinical consequences of WMLs. In addition, ischemic and non-ischemic pathways resulting in WML development should be studied.


Effect of dietary fiber on gut barrier function, gut microbiota, short-chain fatty acids, inflammation, and clinical outcomes in critically ill patients: A systematic review and meta-analysis.
Although some studies have explored the relationships between dietary fiber (DF) supplement and gut barrier function, changes of gut microbiota, and clinical outcomes in critically ill patients, the results were not consistent. The purpose was to explore the effect of DF on gut barrier function, gut microbiota, short-chain fatty acids (SCFAs), inflammation, and clinical outcomes in critically ill patients. A search was performed through five databases from inception to July 12, 2021. Data were expressed as mean difference (MD) or odds ratio (OR) with CI. Twenty-one studies involving 2084 critically ill patients were included. There was a significant reduction in intestinal permeability, demonstrated by lactulose/rhamnose ratio (MD, -0.04; 95% CI, -0.08 to -0.00; P = 0.03) on day 8, C-reactive protein on day 14 (MD, -36.66; 95% CI, -44.40 to -28.93; P < 0.001) and duration of hospital stay (MD, -3.16; 95% CI, -5.82 to -0.49; P < 0.05) after DF supplement. There were no significant differences in SCFA levels, duration of mechanical ventilation, and mortality between two groups. However, subgroup analysis results indicated significant decreases in duration of hospital stay and risk of mortality were seen in the subgroups with a supplementary fiber dose ≥20 g/day (MD, -5.62 [95% CI, -8.04 to -3.21; P < 0.0001]; OR, 0.18 [95% CI, 0.06-0.57; P = 0.004]), as well as in the medical intensive care unit (MD, -4.77 [95% CI, -7.48 to -2.07; P < 0.01]; OR, 0.13 [95% CI, 0.03-0.65; P < 0.05]). DF may improve gut barrier function, modulate intestinal microbiota, decrease systemic inflammatory response, and advance clinical outcomes in critically ill patients.


Higher BMP/Smad sensitivity of tendon-derived stem cells (TDSCs) isolated from the collagenase-induced tendon injury model: possible mechanism for their altered fate in vitro.
Ectopic expression of BMP-2, BMP-4 and BMP-7 was observed in clinical samples of tendinopathy and collagenase-induced (CI) tendon injury rat model. TDSCs isolated from the CI model showed increased non-tenogenic differentiation potential and hence altered fate compared to the TDSCs isolated from the healthy animals (HT) but the mechanism is unclear. We hypothesized that sensitization of the BMP/Smad pathway in TDSCs (CI) might account for this difference. This study aimed to compare the activation state of the BMP/Smad pathway at basal level and upon BMP-2 stimulation in TDSCs (CI) and TDSCs (HT). Collagenase or saline was injected into the patellar tendon of rats for 2 weeks. TDSCs (CI) and TDSCs (HT) were then isolated from the patellar tendon. The mRNA and protein expression of BMPs and BMP receptors in TDSCs (CI) and TDSCs (HT) were analysed. TDSCs from both sources were treated with rhBMP-2 and the expression of phosphorylated and total Smad1/5/8 was examined. Except for the mRNA levels of Bmp7 and Bmpr2, there were significant higher mRNA and protein expression of BMPs and BMP receptors in TDSCs (CI) compared to TDSCs (HT). TDSCs (CI) showed higher basal expression of total Smad1/5/8 but similar basal level of phosphorylated Smad1/5/8 compared to TDSCs (HT). TDSCs (CI) exhibited higher total and phosphorylated Smad1/5/8 upon BMP-2 stimulation. The sensitization of the BMP/Smad pathway in TDSCs (CI) might account for their higher non-tenogenic differentiation potential and hence altered fate. It also provided further support of BMPs and the BMP/Smad signaling pathway in the pathogenesis of tendinopathy.


Quantized H∞ filtering for networked persistent dwell-time switched piecewise-affine systems.
In this study, the problem of quantized H∞ filtering is addressed for networked switched piecewise-affine systems, in which the switching mechanism obeys the persistent dwell-time constraint. To process the measurement output and schedule the transmission sequence for alleviating the burden of the limited communication channel, a logarithmic quantizer is employed, which can further improve the bandwidth utilization in networked switched systems. On the basis of state-space division, the objective is to design a mode-dependent and region-dependent filter that ensuresthe filtering error system is globally uniformly exponentially stable and meets an H∞ performance. By using the mode-dependent Lyapunov function approach and employing appropriate decoupling methods, sufficient conditions for obtaining desired filter gains are deduced. Eventually, two illustrated examples are given to demonstrate the effectiveness of our proposed method.


Effect of border sharpness on the size and position of the focal trough of panoramic x-ray machines.
A resolution test pattern was used to determine the size, position, and centers of the focal troughs of four panoramic x-ray machines. The focal troughs were located at slightly different positions for each machine. The center of each focal trough produced varying degrees of sharpness. The average widths of the focal troughs were not greatly different between machines.


Real-world genomic testing and treatment patterns of newly diagnosed adult acute myeloid leukemia patients within a comprehensive health system.
We evaluated the frequency of genomic testing and treatment patterns by age category in patients with newly diagnosed (ND) acute myeloid leukemia (AML) treated in both academic- and community-based health systems within a single Midwestern State. Retrospective analysis of data from the Indiana University Health System Enterprise Data Warehouse and two local cancer registries, of 629 patients aged ≥18 years with ND AML during 2011-2018. Primary outcome variables were, proportion of patients with genomic analysis and frequency of mutations. Chemotherapy was categorized as "standard induction" or "other chemotherapy"/targeted therapy, and hypomethylating agents. Overall, 13% of ND AML patients between 2011 and 2018 had evidence of a genomic sequencing report with a demonstrated increase to 37% since 2016. Genomic testing was more likely performed in patients: aged ≤60 years than >60 years (45% vs. 30%; p = 0.03), treated in academic versus community hospitals (44% vs. 26%; p = 0.01), and in chemotherapy recipients than non-therapy recipients (46% vs. 19%; p < 0.001). Most common mutations were ASXL1, NPM1, and FLT3. Patients ≥75 years had highest proportion (46%) of multiple (≥3) mutations. Overall, 31.2% of patients with AML did not receive any therapy for their disease. This subgroup was older than chemotherapy recipients (mean age: 71.4 vs. 55.7 years, p < 0.001), and was highest (66.2%) in patients ≥75 years. Our results highlight the unmet medical need to increase access to genomic testing to afford treatment options, particularly to older AML patients in the real-world setting, in this new era of targeted therapies.


Plasma osteopontin acts as a prognostic marker in acute intracerebral hemorrhage patients.
Osteopontin (OPN), a matricellular protein, is greatly generated from brain tissues after acute brain injury. We determine the relationship between plasma OPN concentrations and outcome after acute intracerebral hemorrhage (ICH) in a clinical setting. In this prospective, observational study enrolling 162 ICH patients and 162 healthy controls, hemorrhagic severity was assessed using National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volumes, a poor outcome was defined as modified Rankin Scale >2 at poststroke 90 days, and early neurologic deterioration (END) was defined as an increase of ≥4 points in the NIHSS score or death at 24 h from symptoms onset. Plasma OPN concentrations were significantly higher in patients than in controls (median value, 1287.6 vs. 405.7 pmol/l; P < 0.001). OPN concentrations were strongly correlated with admission NIHSS scores (r value = 0.520) and hematoma volumes (r value = 0.468). Areas under receiver operating characteristic curve for poor outcome and END were 0.811 and 0.753 respectively. Plasma OPN emerged as an independent predictor of functional outcome and END, with odds ratio values of 3.897 and 6.004 respectively. Plasma OPN could serve as a useful prognostic biomarker in ICH.


A willingness-to-pay study of oral epidermal growth factor tyrosine kinase inhibitors in advanced non-small cell lung cancer.
Oral epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are new agents in the treatment of advanced non-small cell lung cancer (NSCLC). Phase II studies demonstrate objective tumor responses and symptom improvement, combined with minimal toxicity and the convenience of an oral agent. We evaluated patient utility through willingness-to-pay (WTP) for these agents in the treatment of advanced NSCLC in Canada. Advanced NSCLC patients and healthy subjects participated in a structured interview and bidding exercise, reviewing current evidence supporting EGFR TKI therapy in advanced NSCLC and patient willingness-to-pay for treatment. Fifty-seven patients and 54 healthy subjects participated. The median amount both groups were willing to pay for a month of oral EGFR TKI therapy was $100 CAD (range $0-5000 per month). A minority of NSCLC patients received employment income, the majority relying on disability, pension income, and social assistance for financial support. Affordability of these agents was a key concern for both advanced NSCLC patients and healthy subjects. Univariate predictors of WTP included marital status, prior chemotherapy treatment, receiving pension income or financial social assistance. In multivariate analysis, only prior chemotherapy remained a significant predictor of WTP (p=0.049). Both advanced NSCLC patients and healthy subjects feel oral EGFR TKIs are worth paying for in the treatment of advanced NSCLC, but are willing to pay only a fraction of the market price. As many advanced NSCLC patients are financially disadvantaged, the potential for restricted access to newer therapies is of concern.


Diagnosis and Pathologic Reporting of Prostate Cancer in the Era of MRI-Targeted Prostate Biopsy.
Historically, the detection of prostate cancer relied upon a systematic yet random sampling of the prostate by transrectal ultrasound guided biopsy. This approach was a nontargeted technique that led to the under detection of cancers at biopsy and the upgrading of cancers at radical prostatectomy. Multiparametric MRI-targeted prostate biopsy allows for an image-directed approach to the identification of prostate cancer. MRI-targeted biopsy of the prostate is superior for the detection of clinically significant prostate cancer. As this technique has become more prevalent among urologists, pathologists need to recognize how this development impacts cancer diagnosis and reporting.


Effect of drying conditions on the quality of IRGA 424 rice.
The objective of this research was to investigate the effects of drying temperature (40, 50, and 60 °C), tempering time (40, 80, and 120 min), and initial moisture content at onset of tempering (15, 17, and 19% dry basis) on head rice yield, milled rice yield, and total processing time of IRGA 424 rice. The most significant effects were the drying temperature and its interaction with initial moisture content at onset of tempering. The optimum conditions predicted to reach the highest total yield (74.1%) included drying at 46.6 °C, 49 min of tempering time, and initial moisture content at onset of tempering of 19%. To achieve the maximum value of whole grain yield (52.9%), drying at 40 °C, 40 min of tempering, and an initial moisture content of 19% at the initiation of tempering were required. Under these conditions, the grain reached a moisture content of 13% in 84 min. Whole-grain rice yields may be maximized through the optimization of the drying process. This may result in a larger fraction of the crop entering the human food chain, enhancing the value of the crop, and resulting in a smaller fraction of broken grain, which commands a lower market value. © 2018 Society of Chemical Industry.