Can Augmented Reality Be Helpful in Pelvic Bone Cancer Surgery? An In Vitro Study.
Application of surgical navigation for pelvic bone cancer surgery may prove useful, but in addition to the fact that research supporting its adoption remains relatively preliminary, the actual navigation devices are physically large, occupying considerable space in already crowded operating rooms. To address this issue, we developed and tested a navigation system for pelvic bone cancer surgery assimilating augmented reality (AR) technology to simplify the system by embedding the navigation software into a tablet personal computer (PC). Using simulated tumors and resections in a pig pelvic model, we asked: Can AR-assisted resection reduce errors in terms of planned bone cuts and improve ability to achieve the planned margin around a tumor in pelvic bone cancer surgery? We developed an AR-based navigation system for pelvic bone tumor surgery, which could be operated on a tablet PC. We created 36 bone tumor models for simulation of tumor resection in pig pelves and assigned 18 each to the AR-assisted resection group and conventional resection group. To simulate a bone tumor, bone cement was inserted into the acetabular dome of the pig pelvis. Tumor resection was simulated in two scenarios. The first was AR-assisted resection by an orthopaedic resident and the second was resection using conventional methods by an orthopaedic oncologist. For both groups, resection was planned with a 1-cm safety margin around the bone cement. Resection margins were evaluated by an independent orthopaedic surgeon who was blinded as to the type of resection. All specimens were sectioned twice: first through a plane parallel to the medial wall of the acetabulum and second through a plane perpendicular to the first. The distance from the resection margin to the bone cement was measured at four different locations for each plane. The largest of the four errors on a plane was adopted for evaluation. Therefore, each specimen had two values of error, which were collected from two perpendicular planes. The resection errors were classified into four grades: ≤ 3 mm; 3 to 6 mm; 6 to 9 mm; and > 9 mm or any tumor violation. Student's t-test was used for statistical comparison of the mean resection errors of the two groups. The mean of 36 resection errors of 18 pelves in the AR-assisted resection group was 1.59 mm (SD, 4.13 mm; 95% confidence interval [CI], 0.24-2.94 mm) and the mean error of the conventional resection group was 4.55 mm (SD, 9.7 mm; 95% CI, 1.38-7.72 mm; p < 0.001). All specimens in the AR-assisted resection group had errors < 6 mm, whereas 78% (28 of 36) of errors in the conventional group were < 6 mm. In this in vitro simulated tumor model, we demonstrated that AR assistance could help to achieve the planned margin. Our model was designed as a proof of concept; although our findings do not justify a clinical trial in humans, they do support continued investigation of this system in a live animal model, which will be our next experiment. The AR-based navigation system provides additional information of the tumor extent and may help surgeons during pelvic bone cancer surgery without the need for more complex and cumbersome conventional navigation systems.


An Integrated Hypothesis on the Domestication of Bactris gasipaes.
Peach palm (Bactris gasipaes Kunth) has had a central place in the livelihoods of people in the Americas since pre-Columbian times, notably for its edible fruits and multi-purpose wood. The botanical taxon includes both domesticated and wild varieties. Domesticated var gasipaes is believed to derive from one or more of the three wild types of var. chichagui identified today, although the exact dynamics and location of the domestication are still uncertain. Drawing on a combination of molecular and phenotypic diversity data, modeling of past climate suitability and existing literature, we present an integrated hypothesis about peach palm's domestication. We support a single initial domestication event in south western Amazonia, giving rise to var. chichagui type 3, the putative incipient domesticate. We argue that subsequent dispersal by humans across western Amazonia, and possibly into Central America allowed for secondary domestication events through hybridization with resident wild populations, and differential human selection pressures, resulting in the diversity of present-day landraces. The high phenotypic diversity in the Ecuadorian and northern Peruvian Amazon suggest that human selection of different traits was particularly intense there. While acknowledging the need for further data collection, we believe that our results contribute new insights and tools to understand domestication and dispersal patterns of this important native staple, as well as to plan for its conservation.


Transposable element-assisted evolution and adaptation to host plant within the Leptosphaeria maculans-Leptosphaeria biglobosa species complex of fungal pathogens.
Many plant-pathogenic fungi have a tendency towards genome size expansion, mostly driven by increasing content of transposable elements (TEs). Through comparative and evolutionary genomics, five members of the Leptosphaeria maculans-Leptosphaeria biglobosa species complex (class Dothideomycetes, order Pleosporales), having different host ranges and pathogenic abilities towards cruciferous plants, were studied to infer the role of TEs on genome shaping, speciation, and on the rise of better adapted pathogens. L. maculans 'brassicae', the most damaging species on oilseed rape, is the only member of the species complex to have a TE-invaded genome (32.5%) compared to the other members genomes (<4%). These TEs had an impact at the structural level by creating large TE-rich regions and are suspected to have been instrumental in chromosomal rearrangements possibly leading to speciation. TEs, associated with species-specific genes involved in disease process, also possibly had an incidence on evolution of pathogenicity by promoting translocations of effector genes to highly dynamic regions and thus tuning the regulation of effector gene expression in planta. Invasion of L. maculans 'brassicae' genome by TEs followed by bursts of TE activity allowed this species to evolve and to better adapt to its host, making this genome species a peculiarity within its own species complex as well as in the Pleosporales lineage.


Feasibility of using the "modified NUTrition Risk In the Critically ill" nutritional risk screening tool to identify nutritionally at-risk patients in an Australian intensive care unit.
The modified NUTrition Risk In the Critically ill (mNUTRIC) score has been demonstrated to accurately quantify the risk of negative patient outcomes and discriminate which patients will benefit the most from nutrition intervention in an intensive care unit (ICU) setting. Calculation of an mNUTRIC score, however, may be time-intensive and unable to be performed within available resources. This may prevent high-risk patients from being identified and reviewed by a dietitian. The purpose of this study was to assess the feasibility of using the mNUTRIC tool to screen for patients at increased nutrition risk and to determine the proportion of those high-risk patients who were reviewed by a dietitian. A retrospective observational study of 260 critically ill patients was conducted between 01/01/2017 and 30/05/2017 in a 20-bed Australian tertiary ICU. Participants included all adults admitted to the ICU for more than 72 h. Feasible implementation was defined as calculating an mNUTRIC score in <5 min per patient where all data were available for >90% of patients. A median time of 4 min and 54 s (interquartile range: 4.3-5.6 min) was required to calculate each mNUTRIC score, with 96% of scores calculated in <10 min. Data were available to calculate mNUTRIC scores for 93% (241/260) of patients. The mNUTRIC tool identified 81 patients at high nutrition risk, 44% (36/81) of whom were not reviewed by a dietitian. There were 21 high-risk patients who were purposefully excluded from dietetic review for various clinical reasons, leaving 15 high-risk patients (19%) who were not reviewed by a dietitian. Implementation of the mNUTRIC tool was not feasible in our ICU, given the set dietetic resources (0.6 full-time equivalent). Shared responsibility of nutrition screening or automating the calculation may be possible solutions to increase feasibility of mNUTRIC screening.


Impact of adherence to treatment with fluticasone propionate/salmeterol in asthma patients.
Low adherence with asthma treatment may be associated with suboptimal outcomes and hence create a treatment gap in the real-life setting. The objective of this study was to assess the long-term association between adherence to treatment with fixed-dose fluticasone propionate/salmeterol (FSC) and the risk of exacerbations and health care utilization in patients with asthma. Observational single cohort study utilizing the Quebec Health Insurance databases. All patients (age >12 years) with a diagnosis of asthma (ICD9-CM 493.xx) between 2001 and 2010 were entered into the study cohort at the time of their first prescription for FSC at any dose. Follow-up continued to the last known claim or death. Adherence to treatment was ascertained as compliance (medication possession ratio ≥80%) and persistence (absence of treatment gap ≥30 days). Outcomes assessed were exacerbations defined as one of the following: use of oral corticosteroid (OCS), emergency room (ER) visit for asthma or hospitalization for asthma. Asthma related health care resource utilizations ascertained were number of prescription claims for rescue medications, ER visits, hospitalizations, intensive care unit (ICU) stay, intubations, and general practitioner (GP) and respirologist visits. A total of 19,126 patients were included in the study. The proportion of compliant and persistent patients were 42.7% and 29.3% respectively. Multivariate logistic regression analyses showed a significantly reduced adjusted odds of exacerbations for compliant (OR = 0.48; 95% CI: 0.44-0.54) and persistent patients (OR = 0.42; 95% CI: 0.38-0.48). Similarly, significantly lower rates of health care utilization were observed for compliant and persistent patients. The results of this large population-based study have shown that increased adherence to treatment with FSC is associated with lower risk for exacerbations, lower rescue medication use and lower health care utilization in asthma patients. Despite the typical limitations of an administrative database study including validity of the diagnosis, the fact that compliance and persistence are calculated based on filled claims which does not guarantee that the patients actually took their medications, and the absence of clinical and laboratory data, the findings have implications for physician and patient awareness of the importance of adherence in the management of asthma.


The CHORUS (Cerivastatin in Heart Outcomes in Renal Disease: Understanding Survival) protocol: a double-blind, placebo-controlled trial in patients with esrd.
The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin)-mediated lowering of serum cholesterol has been associated with a significant reduction in cardiovascular morbidity and mortality. Recent studies suggest that additional non-lipid lowering effects (eg, endothelial stabilization, anti-inflammatory, antithrombogenic) may be important in modulating their effectiveness. Dyslipidemia is common in end-stage renal disease (ESRD), and hemodialysis patients have increased cardiovascular morbidity and mortality. Cerivastatin, a new statin with powerful low-density lipoprotein-cholesterol (LDL-C) lowering capabilities, possesses some unique non-LDL-C-mediated properties that may contribute to a reduction of coronary events in the patient with ESRD. The primary objective of this multicenter multinational study of 1,054 hemodialysis patients is to compare 2 years of treatment with cerivastatin (0.4 mg/d) versus placebo on the composite clinical event rate of myocardial infarction, sudden cardiac death, ischemic stroke, and the need for coronary arterial bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA) procedures in these patients. Changes in lipids, inflammatory proteins including heat stable C-reactive protein (hsCRP), interleukin-6 (IL-6), oncostatin-M, intracellular adhesion molecule-1 (ICAM-1) and monocyte-chemoattractant protein-1 (MCP-1), as well as markers of cardiac muscle pathology, such as troponin I and troponin T, will be assessed in a subset of patients. This study is the first of its kind to assess the effect of a statin on the reduction of cardiovascular morbidity and mortality in an incident hemodialysis population. It will determine whether treatment with cerivastatin can effectively reduce the significant cardiovascular morbidity and mortality.


Lipid requirements of infants: implications for nutrient composition of fortified complementary foods.
Dietary lipids have traditionally been considered as solely part of the exchangeable energy supply. The main consideration in infant nutrition has been the amount of fat that can be tolerated and digested by infants and young children. The significance of the composition of dietary fat has received little attention. Presently, there is a growing interest in the quality of dietary lipid supply in early childhood as a major determinant of growth, infant development and long-term health. Thus, the selection of dietary lipids during the first years of life is now considered to be critically important for health and good nutrition throughout the life course. Over the past decades interest has focused on the role of essential lipids in central nervous system development and of fatty acids and cholesterol in lipoprotein metabolism throughout life. Lipids are structural components of all tissues and are indispensable for cell and plasma membrane synthesis. The brain, retina and other neural tissues are particularly rich in long-chain PUFA. Some (n-6) and (n-3) fatty acids are precursors for eicosanoid formation; these are powerful mediators of numerous cell and tissue functions. Recommendations for infant nutrition and implications of these for the nutrient composition of complementary foods are presented and discussed. There is more to fat than its role as a key fuel in energy metabolism and body energy storage; lipids are essential for tissue growth, cardiovascular health, brain development and function throughout the life course.


The DNA topoisomerase II inhibitor amsacrine as a novel candidate adjuvant in a model of glaucoma filtration surgery.
Treatments for refractory glaucoma include trabeculectomy, in which a filtering bleb is created to reduce aqueous pressure. Mitomycin C (MMC) is often used as an adjuvant to reduce post-trabeculectomy bleb scarring and consequent failure. However, scarring sometimes still occurs. Thus, we searched for more effective trabeculectomy adjuvants with high-throughput screening (HTS) of a library of 1,165 off-patent drug compounds. This revealed that amsacrine (AMSA), a DNA topoisomerase II (TOP2) inhibitor, was the top candidate. Compared to MMC, rabbits that underwent trabeculectomy with 10% AMSA had lower IOP at 42, 56, and 70 days (P < 0.01 at all measurement points) and a higher bleb score at 28, 42, 56, and 70 days (P = < 0.01, 0.04, 0.04, and < 0.01, respectively). Compared to saline, rabbits that received 1% AMSA also had lower IOP and better bleb score at all time points, without a sharp drop in IOP just after surgery (all P < 0.01). Both effects were milder than MMC at 7 days (P = 0.02 and <0.01, respectively). Thus, this study showed that HTS may help identify new, promising uses for off-patent drugs. Furthermore, trabeculectomy with AMSA at a suitable concentration may improve the prognosis after trabeculectomy compared to MMC.


Randomised controlled trial of a tailored information pack for patients undergoing surgery and treatment for rectal cancer.
To evaluate the effects of a tailored information package for rectal cancer patients on satisfaction with information, anxiety and depression and readjustment. The study used a randomised control trial method. Seventy six patients undergoing surgery and treatment for rectal cancer were randomly assigned to an intervention (n = 43) or control group (n = 33). The intervention group received an information pack tailored according to their treatment plan and preferred information. The control group received the information currently given to these patients. Satisfaction with information was measured using the Patient Satisfaction with Cancer Treatment Education (PSCaTE) scale, anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS) and readjustment was measured using the Reintegration to Normal Living Index, at three time points. There was a statistically significant difference between the intervention and control group on pre and post intervention scores with patients in the intervention group expressing a higher level of satisfaction with information than those in the control group at Times 2 and 3 (p = 0.00 for both). The intervention group also had a significantly lower anxiety score than the control group at Time 3 (p = 0.03). There was no difference between depression and readjustment scores in the two groups. The results support the hypothesis that a tailored information pack for patients with rectal cancer will positively affect satisfaction with information. These results will enhance the knowledge base surrounding the provision of tailored information to specific patient groups.


An extract from date palm fruit (Phoenix dactylifera) acts as a co-agonist ligand for the nuclear receptor FXR and differentially modulates FXR target-gene expression in vitro.
Date palm fruit (Phoenix dactylifera) consumption reduces serum triglyceride levels in human subjects. The objective of this study was to prepare an extract from dates and determine whether it acts as a ligand for the farnesoid x receptor (FXR), a nuclear receptor important for maintaining triglyceride and cholesterol homeostasis. Freeze-dried extracts were isolated from California-grown dates (Deglet Noor and Medjool) from the 2014 and 2015 harvests, by means of liquid extraction and solid phase separation. Each date palm extract (DPE) was characterized via HPLC and MALDI-TOF mass spectrometry, and the procyanidin content was qualitatively determined. Extracts were tested to determine their ability to modulate nuclear receptor-mediated transactivation using transient transfection. The effect of DPE on FXR-target genes regulating bile acid absorption and transport was then assessed in vitro, in Caco-2 cells. Characterization reveals that DPE is a rich source of polyphenols including hydroxycinnamic acids, proanthocyanidins, and lipohilic polyphenols, and comprises 13% proanthocyanidins. Transactivation results show that DPE acts as a co-agonist ligand for both mouse and human FXR, wherein it activates bile acid-bound FXR greater than that seen with bile acid alone. Additionally, DPE alone activated a peroxisome proliferator activated receptor alpha (PPARα) chimera in a dose-dependent manner. Consistent with DPE as a co-agonist ligand for FXR, studies in Caco-2 cells reveal that co-incubation with bile acid, dose-dependently enhances the expression of fibroblast growth factor 19 (FGF19), compared to treatment with bile acid alone. In contrast, DPE inhibited bile acid-induced expression of ileal bile acid binding protein (IBABP). Our results demonstrate that DPE acts as a potent co-agonist ligand for FXR, and that it differentially regulates FXR-target gene expression in vitro in human intestinal cells. This study provides novel insight into a potential mechanism by which dates may exert a hypotriglyceridemic effect via FXR and modulation of bile acid homeostasis.


Late detection of a shigellosis outbreak in a school in Madrid.
Even though shigellosis in Spain is rare, an indigenous outbreak is occasionally detected. We describe an outbreak in a school in Madrid caused by person-to-person transmission of Shigella sonnei. After the detection of Shigella sonnei in a stool sample from a 3 year old girl, an investigation at her school was initiated. Questionnaires were distributed to the parents of 520 pupils attending the school. A case was defined as a school case if it was the first case in a child's household, and as a household case if other members of the household had fallen ill first. We identified 88 cases (60 pupils and 28 of their family members). The attack rate (AR) was 12% in the school and 32% in the families. There was a significant association between higher AR and lower age. The outbreak lasted for two months. The length and the shape of the epidemic curve of the 60 cases in pupils suggests person-to-person transmission. Shigella sonnei isolated from 5 different cases were typed by pulsed field gel electrophoresis (PFGE) and was found to be an identical strain. The prolonged duration of the outbreak was probably due to delayed detection, and stopped as soon as control measures were introduced.


Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance.
The MUC1 mucin represents a prime target antigen for cancer immunotherapy because it is abundantly expressed and aberrantly glycosylated in carcinomas. Attempts to generate strong humoral immunity to MUC1 by immunization with peptides have generally failed partly because of tolerance. In this study, we have developed chemoenzymatic synthesis of extended MUC1 TR glycopeptides with cancer-associated O-glycosylation using a panel of recombinant human glycosyltransferases. MUC1 glycopeptides with different densities of Tn and STn glycoforms conjugated to KLH were used as immunogens to evaluate an optimal vaccine design. Glycopeptides with complete O-glycan occupancy (five sites per repeat) elicited the strongest antibody response reacting with MUC1 expressed in breast cancer cell lines in both Balb/c and MUC1.Tg mice. The elicited humoral immune response showed remarkable specificity for cancer cells suggesting that the glycopeptide design holds promise as a cancer vaccine. The elicited immune responses were directed to combined glycopeptide epitopes, and both peptide sequence and carbohydrate structures were important for the antigen. A MAb (5E5) with similar specificity as the elicited immune response was generated and shown to have the same remarkable cancer specificity. This antibody may hold promise in diagnostic and immunopreventive measures.


The ELG1 clamp loader plays a role in sister chromatid cohesion.
Mutations in the ELG1 gene of yeast lead to genomic instability, manifested in high levels of genetic recombination, chromosome loss, and gross chromosomal rearrangements. Elg1 shows similarity to the large subunit of the Replication Factor C clamp loader, and forms a RFC-like (RLC) complex in conjunction with the 4 small RFC subunits. Two additional RLCs exist in yeast: in one of them the large subunit is Ctf18, and in the other, Rad24. Ctf18 has been characterized as the RLC that functions in sister chromatid cohesion. Here we present evidence that the Elg1 RLC (but not Rad24) also plays an important role in this process. A genetic screen identified the cohesin subunit Mcd1/Scc1 and its loader Scc2 as suppressors of the synthetic lethality between elg1 and ctf4. We describe genetic interactions between ELG1 and genes encoding cohesin subunits and their accessory proteins. We also show that defects in Elg1 lead to higher precocious sister chromatid separation, and that Ctf18 and Elg1 affect cohesion via a joint pathway. Finally, we localize both Ctf18 and Elg1 to chromatin and show that Elg1 plays a role in the recruitment of Ctf18. Our results suggest that Elg1, Ctf4, and Ctf18 may coordinate the relative movement of the replication fork with respect to the cohesin ring.


Transcriptional profiling of osseointegration in humans.
To determine the temporal gene expression profile associated with the early healing events during osseointegration in a human model. Nine solid screw-type cylindrical titanium implants, 4 mm long and 2.8 mm wide, with a chemically modified surface (SLActive) were surgically inserted in the retromolar area of nine human volunteers. The devices were removed using a trephine following 4, 7 and 14 days of healing. The tissue surrounding the implant was harvested, total RNA was extracted and microarray analysis was carried out to identify the differences in the transcriptome between days 4, 7 and 14. Gene ontology (GO) analysis of the temporal transcriptional changes was characteristic of a maturing, osteogenic process over the course of the study (4-14 days). At day 4, a gene expression profile associated with proliferation and immuno-inflammatory processes was predominant. However, by day 14, by far the most predominant mechanisms were associated with skeletogenesis, with the GO categories of skeletal system development, bone development and ossification being predominant, with the majority of changes occurring between days 7 and 14. Furthermore, the biological processes of angiogenesis and neurogenesis were also predominant by day 14. In terms of signal transduction, I-κB kinase/NF-κB cascade was predominant at day 4, whereas TGF-β/BMP, Wnt and Notch signalling were all associated with the osteogenic process over the duration of the study. Furthermore, Ras and Rho protein signal transduction was regulated throughout the osseointegration process. The temporal transcriptional changes during osseointegration involve the expression of proliferation and immuno-inflammatory response associated genes during the early stages of osseointegration, which are ultimately replaced by genes associated with the biological processes of skeletogenesis, angiogenesis and neurogenesis. The early immuno-inflammatory changes appear to be regulated via the I-κB kinase/NF-κB cascade, whereas the later osteogenesis-related mechanisms are regulated by TGF-β/BMP, Notch and Wnt signaling.


The volatile compound BinBase mass spectral database.
Volatile compounds comprise diverse chemical groups with wide-ranging sources and functions. These compounds originate from major pathways of secondary metabolism in many organisms and play essential roles in chemical ecology in both plant and animal kingdoms. In past decades, sampling methods and instrumentation for the analysis of complex volatile mixtures have improved; however, design and implementation of database tools to process and store the complex datasets have lagged behind. The volatile compound BinBase (vocBinBase) is an automated peak annotation and database system developed for the analysis of GC-TOF-MS data derived from complex volatile mixtures. The vocBinBase DB is an extension of the previously reported metabolite BinBase software developed to track and identify derivatized metabolites. The BinBase algorithm uses deconvoluted spectra and peak metadata (retention index, unique ion, spectral similarity, peak signal-to-noise ratio, and peak purity) from the Leco ChromaTOF software, and annotates peaks using a multi-tiered filtering system with stringent thresholds. The vocBinBase algorithm assigns the identity of compounds existing in the database. Volatile compound assignments are supported by the Adams mass spectral-retention index library, which contains over 2,000 plant-derived volatile compounds. Novel molecules that are not found within vocBinBase are automatically added using strict mass spectral and experimental criteria. Users obtain fully annotated data sheets with quantitative information for all volatile compounds for studies that may consist of thousands of chromatograms. The vocBinBase database may also be queried across different studies, comprising currently 1,537 unique mass spectra generated from 1.7 million deconvoluted mass spectra of 3,435 samples (18 species). Mass spectra with retention indices and volatile profiles are available as free download under the CC-BY agreement (http://vocbinbase.fiehnlab.ucdavis.edu). The BinBase database algorithms have been successfully modified to allow for tracking and identification of volatile compounds in complex mixtures. The database is capable of annotating large datasets (hundreds to thousands of samples) and is well-suited for between-study comparisons such as chemotaxonomy investigations. This novel volatile compound database tool is applicable to research fields spanning chemical ecology to human health. The BinBase source code is freely available at http://binbase.sourceforge.net/ under the LGPL 2.0 license agreement.


Paradiopatra Ehlers, 1887 (Annelida: Onuphidae) from southwestern Europe with the description of a new species and new ultramorphological data for the genus.
This work recognises five species of Paradiopatra from southwestern Europe, represented in the Bay of Biscay, the Atlantic coasts of Iberia and the western Mediterranean Sea. One species, Paradiopatra florencioi sp. nov., is newly described from the Cantabrian slope, northern Spain. We are presenting detailed diagnoses of all species and report ontogenetic changes of P. bihanica and P. hispanica. Scanning electron microscopy elucidated previously known Methylene Blue or Green staining patterns of the ventral glandular pads as cuticular pores. A dichotomous key to all species is included.


Flexible colloidal nanocrystal electronics.
Nanometer-scale crystals of bulk group IV, III-V, II-VI, IV-VI, I-III-VI2, and metal-halide perovskite semiconductors, dispersed in solvents, are known as colloidal nanocrystals and form an excellent, solution-processable materials class for thin film and flexible electronics. This review surveys the size, composition, and surface chemistry-dependent properties of semiconductor NCs and thin films derived therefrom and provides physico-chemical insight into the recent leaps forward in the performance of NC field-effect transistors. Device design and fabrication methods are described that have enabled the demonstration and scaling up in complexity and area and scaling down in device size of flexible, colloidal nanocrystal integrated circuits. Finally, taking stock of the advances made in the science and engineering of NC systems, challenges and opportunities are presented to develop next-generation, colloidal NC electronic materials and devices, important to their potential in future computational and in Internet of Things applications.


Novel use of ultrasound to examine regional blood flow in the mouse kidney.
Conventional methods used for measuring regional renal blood flow, such as laser-Doppler flowmetry, are highly invasive, and each measurement is restricted to a discrete location. The aim of this study was to determine whether ultrasound imaging in conjunction with enhanced contrast agent (microbubbles; Vevo MicroMarker, VisualSonics) could provide a viable noninvasive alternative. This was achieved by determining changes in renal cortical and medullary rate of perfusion in response to a bolus injection of endothelin-1 (ET-1; 0.6, 1.0, or 2.0 nmol/kg) and comparing these responses to those observed in separate groups of mice with conventional laser-Doppler methods. Intravenous infusion of ET-1 in anesthetized male C57bl/6 mice resulted in a dose-dependent increase in mean arterial pressure and a dose-dependent decrease in total renal blood flow as measured by pulse-wave Doppler. ET-1 infusion resulted in a dose-dependent decrease in regional kidney perfusion as measured by both ultrasound with enhanced contrast agent and laser-Doppler measurements, verifying the use of ultrasound to measure regional kidney perfusion. Noted limitations of ultrasound imaging compared with laser-Doppler flowmetry included a lower degree of sensitivity to changes in tissue perfusion and the inability to assess rapid or transient changes in tissue perfusion. In conclusion, ultrasound represents an effective and noninvasive method for the measurement of relatively short-term, steady-state changes in regional blood flow in the mouse kidney.


Using ancient DNA to study the origins and dispersal of ancestral Polynesian chickens across the Pacific.
The human colonization of Remote Oceania remains one of the great feats of exploration in history, proceeding east from Asia across the vast expanse of the Pacific Ocean. Human commensal and domesticated species were widely transported as part of this diaspora, possibly as far as South America. We sequenced mitochondrial control region DNA from 122 modern and 22 ancient chicken specimens from Polynesia and Island Southeast Asia and used these together with Bayesian modeling methods to examine the human dispersal of chickens across this area. We show that specific techniques are essential to remove contaminating modern DNA from experiments, which appear to have impacted previous studies of Pacific chickens. In contrast to previous reports, we find that all ancient specimens and a high proportion of the modern chickens possess a group of unique, closely related haplotypes found only in the Pacific. This group of haplotypes appears to represent the authentic founding mitochondrial DNA chicken lineages transported across the Pacific, and allows the early dispersal of chickens across Micronesia and Polynesia to be modeled. Importantly, chickens carrying this genetic signature persist on several Pacific islands at high frequencies, suggesting that the original Polynesian chicken lineages may still survive. No early South American chicken samples have been detected with the diagnostic Polynesian mtDNA haplotypes, arguing against reports that chickens provide evidence of Polynesian contact with pre-European South America. Two modern specimens from the Philippines carry haplotypes similar to the ancient Pacific samples, providing clues about a potential homeland for the Polynesian chicken.


Lack of follow-up of prostate-specific antigen test results.
We obtained population estimates of the prevalence of lack of diagnostic follow-up after an abnormal prostate-specific antigen (PSA) result and assessed the role of sociodemographic, access, and risk perception factors on follow-up of abnormal tests. We used data from the 2000 National Health Interview Survey cancer control supplement. For 3,310 men aged 40 or older with a PSA test, 463 men reported an abnormal PSA test. Outcomes were abnormal PSA and lack of diagnostic follow-up in the latter group. Covariates for logistic regression included sociodemographic variables (age, race/ethnicity, and education), access to care (health insurance and usual source), and risk of cancer (family history and perceived risk). Survey analysis procedures accounted for the complex survey design. Abnormal PSA results were associated with age, family history, and perceived risk of cancer. Approximately 15% of men with abnormal PSA tests reported no follow-up. The estimated number was 423,549 (95% confidence interval [CI] 317,755, 529,343). No follow-up was more likely in Hispanic men (odds ratio [OR] = 2.21, 95% CI 1.04, 4.70) and men without insurance (OR=6.56, 95% CI 2.02, 21.29), but less likely in men with a family history of prostate cancer or higher perceived risk of cancer. Substantial numbers of men had no follow-up of abnormal PSA tests. Primary care physicians should assess continuity of care following abnormal PSA results. Data about prostate cancer screening and follow-up are needed to support clinical and policy decisions.


Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study.
Fibroblast growth factor receptor (FGFR) 2 gene alterations are involved in the pathogenesis of cholangiocarcinoma. Pemigatinib is a selective, potent, oral inhibitor of FGFR1, 2, and 3. This study evaluated the safety and antitumour activity of pemigatinib in patients with previously treated, locally advanced or metastatic cholangiocarcinoma with and without FGFR2 fusions or rearrangements. In this multicentre, open-label, single-arm, multicohort, phase 2 study (FIGHT-202), patients aged 18 years or older with disease progression following at least one previous treatment and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 recruited from 146 academic or community-based sites in the USA, Europe, the Middle East, and Asia were assigned to one of three cohorts: patients with FGFR2 fusions or rearrangements, patients with other FGF/FGFR alterations, or patients with no FGF/FGFR alterations. All enrolled patients received a starting dose of 13·5 mg oral pemigatinib once daily (21-day cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, withdrawal of consent, or physician decision. The primary endpoint was the proportion of patients who achieved an objective response among those with FGFR2 fusions or rearrangements, assessed centrally in all patients who received at least one dose of pemigatinib. This study is registered with ClinicalTrials.gov, NCT02924376, and enrolment is completed. Between Jan 17, 2017, and March 22, 2019, 146 patients were enrolled: 107 with FGFR2 fusions or rearrangements, 20 with other FGF/FGFR alterations, 18 with no FGF/FGFR alterations, and one with an undetermined FGF/FGFR alteration. The median follow-up was 17·8 months (IQR 11·6-21·3). 38 (35·5% [95% CI 26·5-45·4]) patients with FGFR2 fusions or rearrangements achieved an objective response (three complete responses and 35 partial responses). Overall, hyperphosphataemia was the most common all-grade adverse event irrespective of cause (88 [60%] of 146 patients). 93 (64%) patients had a grade 3 or worse adverse event (irrespective of cause); the most frequent were hypophosphataemia (18 [12%]), arthralgia (nine [6%]), stomatitis (eight [5%]), hyponatraemia (eight [5%]), abdominal pain (seven [5%]), and fatigue (seven [5%]). 65 (45%) patients had serious adverse events; the most frequent were abdominal pain (seven [5%]), pyrexia (seven [5%]), cholangitis (five [3%]), and pleural effusion (five [3%]). Overall, 71 (49%) patients died during the study, most frequently because of disease progression (61 [42%]); no deaths were deemed to be treatment related. These data support the therapeutic potential of pemigatinib in previously treated patients with cholangiocarcinoma who have FGFR2 fusions or rearrangements. Incyte Corporation.


Turning up the heat on wormlike micelles with a hydrotopic salt in microfluidics.
In equilibrium, wormlike micelles can transition from entangled to branched structures with increasing surfactant concentrations and ionic strength. Under flow conditions, structural transition of micellar solutions can follow very different trajectories. In this study we consider the flow of a semi-dilute wormlike micellar solution through an array of microposts, with focus on its rheological and microstructural evolutions. Specifically, the micellar solution (precursor) contains cationic surfactant cetyltrimethylammonium bromide (CTAB) and hydrotropic organic salt 3-hydroxynaphthalene-2-carboxylate (SHNC). We report the formation of a flow induced structured phase (FISP), with entangled, branched, and multi-connected micellar bundles, evidenced by electron microscopy and small-angle neutron scattering (SANS). By integrating gold-etched microheaters with the micropost design in a microfluidic device, we investigate the localized temperature effect on both the precursor and FISP, with complementary investigations from SANS. We observe that the FISP does not completely disintegrate at high temperatures, whereas, the precursor exhibits shortening of wormlike micelles as temperature increases. We also correlate the microstructure of both FISP and precursor with two point passive microrheology and bulk rheology characterizations.


The effect of reactor geometry on frontal polymerization spin modes.
Using reactors of different sizes and geometries the dynamics of the frontal polymerization of 1,6-hexanediol diacrylate (HDDA) and pentaerythritol tetraacrylate (PETAC), with ammonium persulfate as the initiator were studied. For this system, the frontal polymerization exhibits complex behavior that depends on the ratio of the monomers. For a particular range of monomers concentration, the polymerization front becomes nonplanar, and spin modes appear. By varying the reactor diameter, we experimentally confirmed the expected shift of the system to a greater number of "hot spots" for larger diameters. For square test tubes a "zig-zag" mode was observed for the first time in frontal polymerization. We confirmed the viscosity-dependence of the spin mode instabilities. We also observed novel modes in cylinder-inside-cylinder reactors. Lastly, using a conical reactor with a continuously varying diameter, we observed what may be evidence for bistability depending on the direction of propagation. We discuss these finding in terms of the standard linear stability analysis for propagating fronts. (c) 2002 American Institute of Physics.


alpha-Tropomyosin mutations Asp(175)Asn and Glu(180)Gly affect cardiac function in transgenic rats in different ways.
To study the mechanisms by which missense mutations in alpha-tropomyosin cause familial hypertrophic cardiomyopathy, we generated transgenic rats overexpressing alpha-tropomyosin with one of two disease-causing mutations, Asp(175)Asn or Glu(180)Gly, and analyzed phenotypic changes at molecular, morphological, and physiological levels. The transgenic proteins were stably integrated into the sarcomere, as shown by immunohistochemistry using a human-specific anti-alpha-tropomyosin antibody, ARG1. In transgenic rats with either alpha-tropomyosin mutation, molecular markers of cardiac hypertrophy were induced. Ca(2+) sensitivity of cardiac skinned-fiber preparations from animals with mutation Asp(175)Asn, but not Glu(180)Gly, was decreased. Furthermore, elevated frequency and amplitude of spontaneous Ca(2+) waves were detected only in cardiomyocytes from animals with mutation Asp(175)Asn, suggesting an increase in intracellular Ca(2+) concentration compensating for the reduced Ca(2+) sensitivity of isometric force generation. Accordingly, in Langendorff-perfused heart preparations, myocardial contraction and relaxation were accelerated in animals with mutation Asp(175)Asn. The results allow us to propose a hypothesis of the pathogenetic changes caused by alpha-tropomyosin mutation Asp(175)Asn in familial hypertrophic cardiomyopathy on the basis of changes in Ca(2+) handling as a sensitive mechanism to compensate for alterations in sarcomeric structure.


Effect of gelam honey on the oxidative stress-induced signaling pathways in pancreatic hamster cells.
Background. Oxidative stress induced by reactive oxygen and nitrogen species is critically involved in the impairment of β -cell function during the development of diabetes. Methods. HIT-T15 cells were cultured in 5% CO2 and then preincubated with Gelam honey extracts (20, 40, 60, and 80 µg/mL) as well as quercetin (20, 40, 60, and 80 µM), prior to stimulation by 20 and 50 mM of glucose. Cell lysate was collected to determine the effect of honey extracts and quercetin on the stress activated NF- κ B, MAPK pathways, and the Akt (ser473) activated insulin signaling pathway. Results. HIT-T15 cells cultured under hyperglycemic conditions demonstrated insulin resistance with a significant increase in the levels of MAPK, NF- κ B, and IRS-1 serine phosphorylation (ser307); however, Akt expression and insulin contents are significantly decreased. Pretreatment with quercetin and Gelam honey extract improved insulin resistance and insulin content by reducing the expression of MAPK, NF- κ B, and IRS-1 serine phosphorylation (ser307) and increasing the expression of Akt significantly. Conclusion. Gelam honey-induced differential expression of MAPK, NF- κ B, IRS-1 (ser307), and Akt in HIT-T15 cells shows that Gelam honey exerts protective effects against diabetes- and hyperglycemia-induced oxidative stress by improving insulin content and insulin resistance.


Cellular angiofibroma of the vulva: case report with clinicopathological and immunohistochemistry study.
Cellular angiofibroma of the vulva is a rare tumor that was first described in 1997. It occurs in middle-aged women (average age: 47 years), has small size (< 3 cm) and well-circumscribed margins. We describe a case in a 51-year-old woman whose preoperative diagnosis was confounded with Bartholin's glandular cyst. The neoplasia was well delimited and made up of three characteristic components: fusiform cells forming small fascicles, numerous blood vessels and adipose tissue interspersed between the fusiform cells. The stroma cells were positive for vimentin and negative for CD34, protein S-100, actin and desmin. The differential diagnoses for this tumor include aggressive angiomyxoma, angiomyofibroblastoma, lipoma of fusiform cells, solitary fibrous tumor, perineurioma and leiomyoma.


Relationships of diet-related blood parameters and blood lead levels with psychopathology and aggression in forensic psychiatric inpatients.
Earlier studies have suggested associations between diet-related blood parameters and both aggression and psychopathological symptoms, but little is known about this in forensic psychiatric inpatients. This article aims to explore the levels of diet-related blood parameters and their relationship to aggressive behaviour and/or psychopathology among Dutch forensic psychiatric inpatients. Minerals, vitamins, lead and fatty acid levels were measured in blood samples from 51 inpatients, well enough to consent and participate in the study, from a possible total of 99. Levels of aggression and psychopathology were assessed using questionnaires, observation instruments and clinical data. Associations between blood parameters and behavioural measures were calculated. Low average levels of vitamin D3 and omega (ω)-3 fatty acids were found, with nearly two-thirds of the patients having below recommended levels of D3 , while vitamin B6 levels were high. Magnesium, iron, zinc, copper and lead were overall within reference values, but copper/zinc ratios were high. Several significant associations between levels of fatty acid measures and both aggression and psychopathology were observed. In our sample of forensic psychiatric inpatients, fatty acids - but not mineral or vitamin levels - were associated with aggression and psychopathology. A potentially causal link between fatty acids and aggression could be tested in a randomised, placebo-controlled trial of fish oil supplements. General health of such patients might be improved by better vitamin D status (increased sun exposure and/or supplement use) and better ω-3 fatty acid status (oily fish or fish oil consumption), but discouraging unnecessary self-prescription of B vitamins where necessary. Copyright © 2015 John Wiley & Sons, Ltd.


Relation of cholesterol-stimulated Staphylococcus aureus growth to chronic blepharitis.
Many types of chronic blepharitis have been believed to be primarily microbial in origin; however, it was proposed that differences and changes in lipid composition of meibomian secretion may be the initiating factor in some of these. It was recently reported that there are two subgroups of normals, those whose meibomian secretions contain high levels of cholesterol esters and those whose secretions contain very low levels of these esters. Thus, these subgroups of normals were defined on the basis of detailed lipid analyses of meibomian secretions from individuals showing no clinical signs of chronic blepharitis. All secretions from patients in the various disease groups contain high levels of these esters. Based on previous observations that in some chronic blepharitis disease groups certain Staphylococcus species were capable of hydrolyzing cholesterol esters, the authors tested the hypothesis that the resulting cholesterol might affect growth of Staphylococcus aureus. Staphylococcus aureus growth stimulation in Mueller-Hinton broth by cholesterol was determined by colony forming units. Growth stimulation by cholesterol and other additives was also determined by the optical density 650 nm method. Statistical analyses included analysis of variance and the Student's t test. Cholesterol stimulated Staphylococcus aureus growth was significant during the first 24 hr period (20% increase at 25 microM cholesterol, P < 0.02), and for the total 48 hr period (40% increase at 400 microM cholesterol, P < 0.005) when compared to the respective control. Growth stimulation, determined by OD at 650 nm, in the presence of cholesterol was significantly greater (P < 0.02) than that in the presence of either sitosterol or cholestanol when the sterol concentration was 190 microM. These results suggest that the presence and hydrolysis of cholesterol esters of meibomian secretions may contribute to the proliferation of Staphylococcus spp, especially Staphylococcus aureus, observed in some chronic blepharitis disease groups.


PD-L1 and PD-L2 differ in their molecular mechanisms of interaction with PD-1.
The programmed death-1 (PD-1) molecule is involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. PD-1 interacts with two ligands, PD-L1 and PD-L2. We have investigated the molecular mechanisms of PD-1 interactions with its ligands by surface plasmon resonance and cell surface binding as well as the ability of the two ligands to compete for PD-1 binding. PD-L1 and PD-L2 bound PD-1 with comparable affinities, but striking differences were observed at the level of the association and dissociation characteristics. PD-L1, but not PD-L2, had a delayed interaction reminiscent of a phenomenon of conformational transition. These mechanisms were confirmed by using PD-L1 mAbs that delayed the dissociation of PD-L1 from PD-1. This mechanism was not restricted to PD-1 binding since PD-L1 behaved in a similar manner with its second ligand, CD80. Finally, we could demonstrate that PD-L1 and PD-L2 competed for PD-1 binding and conversely, an antagonist PD-1 mAb blocked both PD-L1 and PD-L2 binding to PD-1 and strongly enhanced T-cell proliferation. These data further emphasize the differential molecular mechanisms of interaction of PD-L1 and PD-L2 with PD-1, and suggest possible new approach for the therapy of chronic infection, cancer and transplantation.


Fimbrial profiles predict virulence of uropathogenic Escherichia coli strains: contribution of ygi and yad fimbriae.
Escherichia coli, a cause of ∼90% of urinary tract infections (UTI), utilizes fimbrial adhesins to colonize the uroepithelium. Pyelonephritis isolate E. coli CFT073 carries 12 fimbrial operons, 5 of which have never been studied. Using multiplex PCR, the prevalence of these 12 and 3 additional fimbrial types was determined for a collection of 303 E. coli isolates (57 human commensal, 32 animal commensal, 54 asymptomatic bacteriuria, 45 complicated UTI, 38 uncomplicated cystitis, and 77 pyelonephritis). The number of fimbrial types per E. coli isolate was distributed bimodally: those with low (3.2 ± 1.1) and those with high (8.3 ± 1.3) numbers of fimbrial types (means ± standard errors of the means). The fimbrial genes ygiL, yadN, yfcV, and c2395 were significantly more prevalent among urine isolates than human commensal isolates. The effect of deletion of Ygi and Yad fimbrial operons on growth, motility, biofilm formation, adherence to immortalized human epithelial cells, and pathogenesis in the mouse model of UTI was examined. Yad fimbriae were necessary for wild-type levels of adherence to a bladder epithelial cell line and for biofilm formation. Deletion of these fimbrial genes increased motility. Ygi fimbriae were necessary for wild-type levels of adherence to a human embryonic kidney cell line, biofilm formation, and in vivo fitness in the urine and kidneys. Complementation of each fimbrial mutant restored wild-type levels of motility, biofilm formation, adherence and, for ygi, in vivo fitness. A double deletion strain, Δygi Δyad, was attenuated in the urine, bladder, and kidneys in the mouse model, demonstrating that these fimbriae contribute to uropathogenesis.


A cis-regulatory mutation of PDSS2 causes silky-feather in chickens.
Silky-feather has been selected and fixed in some breeds due to its unique appearance. This phenotype is caused by a single recessive gene (hookless, h). Here we map the silky-feather locus to chromosome 3 by linkage analysis and subsequently fine-map it to an 18.9 kb interval using the identical by descent (IBD) method. Further analysis reveals that a C to G transversion located upstream of the prenyl (decaprenyl) diphosphate synthase, subunit 2 (PDSS2) gene is causing silky-feather. All silky-feather birds are homozygous for the G allele. The silky-feather mutation significantly decreases the expression of PDSS2 during feather development in vivo. Consistent with the regulatory effect, the C to G transversion is shown to remarkably reduce PDSS2 promoter activity in vitro. We report a new example of feather structure variation associated with a spontaneous mutation and provide new insight into the PDSS2 function.


Immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF).
The Immunodeficiency, Centromeric region instability, Facial anomalies syndrome (ICF) is a rare autosomal recessive disease described in about 50 patients worldwide and characterized by immunodeficiency, although B cells are present, and by characteristic rearrangements in the vicinity of the centromeres (the juxtacentromeric heterochromatin) of chromosomes 1 and 16 and sometimes 9. Other variable symptoms of this probably under-diagnosed syndrome include mild facial dysmorphism, growth retardation, failure to thrive, and psychomotor retardation. Serum levels of IgG, IgM, IgE, and/or IgA are low, although the type of immunoglobulin deficiency is variable. Recurrent infections are the presenting symptom, usually in early childhood. ICF always involves limited hypomethylation of DNA and often arises from mutations in one of the DNA methyltransferase genes (DNMT3B). Much of this DNA hypomethylation is in 1qh, 9qh, and 16qh, regions that are the site of whole-arm deletions, chromatid and chromosome breaks, stretching (decondensation), and multiradial chromosome junctions in mitogen-stimulated lymphocytes. By an unknown mechanism, the DNMT3B deficiency that causes ICF interferes with lymphogenesis (at a step after class switching) or lymphocyte activation. With the identification of DNMT3B as the affected gene in a majority of ICF patients, prenatal diagnosis of ICF is possible. However, given the variety of DNMT3B mutations, a first-degree affected relative should first have both alleles of this gene sequenced. Treatment almost always includes regular infusions of immunoglobulins, mostly intravenously. Recently, bone marrow transplantation has been tried.


Relapsing encephalopathy in a patient with alpha-methylacyl-CoA racemase deficiency.
Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare disorder of fatty acid metabolism which has recently been described in three adult cases. We have identified a further patient with clinical features of a relapsing encephalopathy, seizures and cognitive decline over a 40 year period. Biochemical studies revealed grossly elevated plasma pristanic acid levels, and a deficiency of AMACR in skin fibroblasts. Sequence analysis of AMACR cDNA identified a homozygous point mutation (c154T>C). This case adds to the phenotypic variation seen in this peroxisomal disorder and highlights the importance of screening for plasma pristanic acid levels in patients with unexplained relapsing encephalopathies.


Microbiological investigation of an industrial ultra pure supply water plant using cultivation-based and cultivation-independent methods.
Ultra pure waters (UPW), characterized by extremely low salt and nutrient concentrations, can suffer from microbial contamination which causes biofouling and biocorrosion, possibly leading to reduced lifetime and increased operational costs. Samples were taken from an ultra pure supply water producing plant of a power plant. Scanning electron microscopic examination was carried out on the biofilms formed in the system. Biofilm, ion exchange resin, and water samples were characterized by culture-based methods and molecular fingerprinting (terminal restriction fragment length polymorphism [T-RFLP] analysis and molecular cloning). Identification of bacteria was based on 16S rDNA sequence comparison. A complex microbial community structure was revealed. Nearly 46% of the clones were related to as yet uncultured bacteria. The community profiles of the water samples were the most diverse and most of bacteria were recruited from bacterial communities of tube surface and ion exchange resin biofilms. Microbiota of different layers of the mixed bed ion exchange resin showed the highest similarity. Most of the identified taxa (dominated by β-Proteobacteria) could take part in microbially influenced corrosion.


Psychophysics of reading. IV. Wavelength effects in normal and low vision.
Does the color of text influence its legibility? There are reasons why it may do so for specific groups of low-vision observers. We used psychophysical methods to measure the effects of wavelength on the reading performance of four normal observers, two dichromats, and twenty-five low-vision observers. Reading rates were measured for text scanned across the face of a television (TV) monitor. We compared performance under four luminance-matched conditions in which sets of neutral-density and Wratten color filters were placed in front of the TV screen--blue (lambda max = 430 nm), green (lambda max = 550 nm), red (lambda max = 650 nm), and gray. Under photopic conditions, the reading rates of normal subjects were independent of wavelength, with the exception of characters near the acuity limit. At lower luminances, wavelength effects could be explained by the shift from photopic to scotopic vision. It was hypothesized that light scatter or absorption in eyes with cloudy ocular media would result in depressed performance in the blue. Only one of seven subjects demonstrated this effect, which we traced to wavelength-specific absorption. Observers with advanced photoreceptor disorders tended to read blue text faster than red text. This could not be explained on the basis of photopic spectral sensitivities alone. Finally, the presence of central or peripheral field loss was not predictive of wavelength-specific effects in reading. On the whole, wavelength only occasionally plays a significant role in reading. When it does, performance tends to be depressed either in the red or the blue and to be nearly optimal for green or gray.


Microsurgical management of spinal schwannomas: evaluation of 128 cases.
The authors conducted a study to evaluate the clinical characteristics and surgical outcomes in patients with spinal schwannomas and without neurofibromatosis (NF). The data obtained in 128 patients who underwent resection of spinal schwannomas were analyzed. All cases with neurofibromas and those with a known diagnosis of NF Type 1 or 2 were excluded. Karnofsky Performance Scale (KPS) scores were used to compare patient outcomes when examining the anatomical location and spinal level of the tumor. The neurological outcome was further assessed using the Medical Research Council (MRC) muscle testing scale. Altogether, 131 schwannomas were treated in 128 patients (76 males and 52 females; mean age 47.7 years). The peak prevalence is seen between the 3rd and 6th decades. Pain was the most common presenting symptom. Gross-total resection was achieved in 127 (97.0%) of the 131 lesions. The nerve root had to be sacrificed in 34 cases and resulted in minor sensory deficits in 16 patients (12.5%) and slight motor weakness (MRC Grade 3/5) in 3 (2.3%). The KPS scores and MRC grades were significantly higher at the time of last follow-up in all patient groups (p = 0.001 and p = 0.005, respectively). Spinal schwannomas may occur at any level of the spinal axis and are most commonly intradural. The most frequent clinical presentation is pain. Most spinal schwannomas in non-NF cases can be resected totally without or with minor postoperative deficits. Preoperative autonomic dysfunction does not improve significantly after surgical management.


Identification of a novel conjugative plasmid in mycobacteria that requires both type IV and type VII secretion.
Conjugative plasmids have been identified in a wide variety of different bacteria, ranging from proteobacteria to firmicutes, and conjugation is one of the most efficient routes for horizontal gene transfer. The most widespread mechanism of plasmid conjugation relies on different variants of the type IV secretion pathway. Here, we describe the identification of a novel type of conjugative plasmid that seems to be unique for mycobacteria. Interestingly, while this plasmid is efficiently exchanged between different species of slow-growing mycobacteria, including Mycobacterium tuberculosis, it could not be transferred to any of the fast-growing mycobacteria tested. Genetic analysis of the conjugative plasmid showed the presence of a locus containing homologues of three type IV secretion system components and a relaxase. In addition, a new type VII secretion locus was present. Using transposon insertion mutagenesis, we show that in fact both these secretion systems are essential for conjugation, indicating that this plasmid represents a new class of conjugative plasmids requiring two secretion machineries. This plasmid could form a useful new tool to exchange or introduce DNA in slow-growing mycobacteria. Conjugative plasmids play an important role in horizontal gene transfer between different bacteria and, as such, in their adaptation and evolution. This effect is most obvious in the spread of antibiotic resistance genes. Thus far, conjugation of natural plasmids has been described only rarely for mycobacterial species. In fact, it is generally accepted that M. tuberculosis does not show any recent sign of horizontal gene transfer. In this study, we describe the identification of a new widespread conjugative plasmid that can also be efficiently transferred to M. tuberculosis. This plasmid therefore poses both a threat and an opportunity. The threat is that, through the acquisition of antibiotic resistance markers, this plasmid could start a rapid spread of antibiotic resistance genes between pathogenic mycobacteria. The opportunity is that we could use this plasmid to generate new tools for the efficient introduction of foreign DNA in slow-growing mycobacteria.


The orientations of cytochrome c in the highly dynamic complex with cytochrome b5 visualized by NMR and docking using HADDOCK.
The interaction of bovine microsomal ferricytochrome b5 with yeast iso-1-ferri and ferrocytochrome c has been investigated using heteronuclear NMR techniques. Chemical-shift perturbations for 1H and 15N nuclei of both cytochromes, arising from the interactions with the unlabeled partner proteins, were used for mapping the interacting surfaces on both proteins. The similarity of the binding shifts observed for oxidized and reduced cytochrome c indicates that the complex formation is not influenced by the oxidation state of the cytochrome c. Protein-protein docking simulations have been performed for the binary cytochrome b5-cytochrome c and ternary (cytochrome b5)-(cytochrome c)2 complexes using a novel HADDOCK approach. The docking procedure, which makes use of the experimental data to drive the docking, identified a range of orientations assumed by the proteins in the complex. It is demonstrated that cytochrome c uses a confined surface patch for interaction with a much more extensive surface area of cytochrome b5. Taken together, the experimental data suggest the presence of a dynamic ensemble of conformations assumed by the proteins in the complex.


A conceptual model of physician-patient relationships: a qualitative study.
In any clinical encounter, an effective physician-patient relationship is necessary for achieving the desired outcome. This outcome is successful treatment, and therefore, the relationship should be a healing one. In addition, in the Islamic view, the physician is a manifestation of God's healing attribute, which is usually undermined in everyday therapeutic communications. Yet there are few empirical data about this experience and how it occurs in the clinical context. This study was conducted to develop a model of physician-patient relationship, with the healing process at its core. Our goal was to explain the nature and characteristics of this encounter. In Islamic teachings, healing is defined as "cure" when possible and if not, reducing pain and suffering and ultimately finding a meaning in the illness experience. This study was a qualitative inquiry. Data were collected through 17 open-ended, semi-structured interviews with physicians who had an effective relationship with their patients. The participants' experiences and their perception regarding the relationship were subjected to grounded theory content analysis. For establishing the trustworthiness of the data collection and analysis we used triangulation, peer review, and member checking. The findings showed that the components of the patient-physician healing relationship could be categorized in the four key processes of valuing the patient as a person, effective management of power imbalance, commitment, and the physician's competence and character. This leads to forming the three necessary relational elements of trust, peace and hope, and being acknowledged. Their importance has been better demonstrated in a relationship which incorporates the spiritual aspects of patient care and also physician's satisfaction. The physician-patient relationship has a central role in patient outcome. This relationship has an understandable structure and its components may have an effective impact on promoting the patient's experience of the health system.


Arteriopathy Influences Pediatric Ischemic Stroke Presentation, but Sickle Cell Disease Influences Stroke Management.
Background and Purpose- Sickle cell disease (SCD) and arteriopathy are pediatric stroke risk factors that are not mutually exclusive. The relative contributions of sickled red blood cells and arteriopathy to stroke risk are unknown, resulting in unclear guidelines for primary and secondary stroke prevention when both risk factors are present. We hypothesized that despite similarities in clinical presentation and radiographic appearance of arteriopathies, stroke evaluation and management differ in children with SCD compared with those without SCD. Methods- We compared presentation and management of children with and without SCD enrolled in the IPSS (International Pediatric Stroke Study) with acute arterial ischemic stroke, according to SCD and arteriopathy status. Regression modeling determined relative contribution of SCD and arteriopathy in variables with significant frequency differences. Results- Among 930 childhood arterial ischemic strokes, there were 98 children with SCD, 67 of whom had arteriopathy, and 466 without SCD, 392 of whom had arteriopathy. Arteriopathy, regardless of SCD status, increased likelihood of hemiparesis (odds ratio [OR], 1.94; 95% CI, 1.46-2.56) and speech abnormalities (OR, 1.67; 95% CI, 1.29-2.19). Arteriopathy also increased likelihood of headache but only among those without SCD (OR, 1.89; 95% CI, 1.40-2.55). Echocardiograms were less frequently obtained in children with SCD (OR, 0.58; 95% CI, 0.37-0.93), but the frequency of identified cardiac abnormalities was similar in both groups ( P=0.57). Children with SCD were less likely to receive antithrombotic therapy, even in the presence of arteriopathy (OR, 0.14; 95% CI, 0.08-0.22). Arteriopathy was associated with a significantly higher likelihood of antithrombotic therapy in children without SCD (OR, 5.36; 95% CI, 3.55-8.09). Conclusions- Arteriopathy, and not SCD status, was most influential of stroke presentation. However, SCD status influenced stroke management because children with SCD were less likely to have echocardiograms or receive antithrombotic therapy. Further work is needed to determine whether management differences are warranted.


Brown spider venom toxins: what are the functions of astacins, serine proteases, hyaluronidases, allergens, TCTP, serpins and knottins?
Accidents caused by the bites of brown spiders (Loxosceles) generate a clinical condition that often includes a threatening necrotic skin lesion near the bite site along with a remarkable inflammatory response. Systemic disorders such as hemolysis, thrombocytopenia, and acute renal failure may occur, but are much less frequent than the local damage. It is already known that phospholipases D, highly expressed toxins in Loxosceles venom, can induce most of these injuries. However, this spider venom has a great range of toxins that probably act synergistically to enhance toxicity. The other protein classes remain poorly explored due to the difficulty in obtaining sufficient amounts of them for a thorough investigation. They include astacins (metalloproteases), serine proteases, knottins, translationally controlled tumor proteins (TCTP), hyaluronidases, allergens and serpins. It has already been shown that some of them, according to their characteristics, may participate to some extent in the development of loxoscelism. In addition, all of these toxins present potential application in several areas. The present review article summarizes information regarding some functional aspects of the protein classes listed above, discusses the directions that could be taken to materialize a comprehensive investigation on each of these toxins as well as highlights the importance of exploring the full venom repertoire.


On the issues related to compliance assessment of ICNIRP 2010 basic restrictions.
This article discusses technical issues related to compliance assessment of ICNIRP 2010 basic restrictions. Several difficulties are identified in this study when assessing the spatial average and 99th percentile value of the electric field. These issues are mainly attributed to the lack of clarity in the guideline specifications, which leads to inadequate or irreproducible results. Effects on compliance results due to such ambiguous procedures are hereby investigated, with particular focus on technical issues rather than biological ones. Examples spanning from simple canonical test cases to realistic applications have been selected to highlight the strong variability in dosimetry results. Based on our findings, revisiting the ICNIRP 2010 guidelines is strongly recommended, and proposed alternative solutions are outlined.


Occurrence of pathogenicity island I(APEC-O1) genes among Escherichia coli implicated in avian colibacillosis.
Colibacillosis caused by avian pathogenic Escherichia coli (APEC) is a leading cause of economic loss to the poultry industry worldwide. The ability of APEC to cause disease is determined by certain virulence markers, some of which are located on pathogenicity islands (PAls). We recently described one such PAI in an APEC O1:K1 strain (APEC-O1). This PAI, termed PAI I(APEC-O1), carries the genes of the pap operon, a region similar to the tia invasion determinant of enterotoxigenic E coli; ireA, a gene that encodes an iron-responsive element; and a novel 1.5-kb region, ORF 54. Here, the occurrence of six selected loci of PAI I(APEC-O1) (papA, papC, papG, ireA, tia, and ORF 54) among APEC and fecal E. coli strains from apparently healthy chickens (avian commensal E. coli) was determined using polymerase chain reaction (PCR) techniques. None of the commensal E. coli was positive for all six traits, whereas 7.2% of the APEC isolates were positive for all the traits. Although there was no significant difference in the occurrence of ORF 54 among APEC and commensal E. coli, tia, ireA, papC, and papG genes were predominantly present in APEC rather than in avian commensal E. coli. papA was detected in only 6.3% of APEC, perhaps because of the presence of allelic variants of the gene. Additionally, the presence of all six traits was tested with PCR in APEC isolates collected in the 1980s, and these results were compared with those obtained with the APEC isolated in the 1990s. There was no significant difference in the occurrence of tia, ireA, papC, papG, and ORF 54 between APEC isolates collected during the different decades. However, papA was more frequently present in APEC from the 1980s than it was in APEC from the 1990s. Phylogenetic group of an isolate did not correlate with pathogenicity or the presence of PAI traits, except that more APEC of the low-pathogenicity group belonged to the phylogenetic group B1. However, PAI traits occurred more frequently in isolates belonging to the intermediate- and high-pathogenicity groups than in isolates of low pathogenicity.


Balance of power--dynamic regulation of chromatin in plant development.
Chromatin states profoundly determine and maintain gene activity and gene repression in eukaryotic organisms. Regulation of chromatin involves chromatin remodeling, chromatin modifications and exchange of chromatin components and is linked to DNA methylation in some cases. In plants and other organisms, chromatin proteins control many developmental pathways, integrate changes in the environment and can confer a cellular memory of these cues. Here, we review the molecular mechanisms that provide a dynamic regulation of chromatin in a cell. In addition, we discuss how chromatin needs to be flexibly regulated during plant growth to confer stable expression states that can occasionally be reset, e.g., owing to changes in the environment and progression of development.


A diagnostic challenge: dilated pupil.
Dilated pupil is a diagnostic challenge encountered by neurologists and ophthalmologists. The aim of this review is to provide an overview of the current data and guidelines concerning dilated pupils. The majority of recent reports on dilated pupils are indicative of several medical conditions that require evaluation. The topical synthetic parasympatholytic agents; local contamination of antihistamines with their antimuscarinic effects; atropine, scopolamine, and tropane alkaloids in all species of Datura plants may produce mydriasis. The causes of pupillary dilatation can be unilateral, bilateral, and transient. The clinical approach to dilated pupils requires stepwise evaluation, and based on the findings, unnecessary and costly procedures can be avoided.


Enhanced lithium dendrite suppressing capability enabled by a solid-like electrolyte with different-sized nanoparticles.
A solid-like electrolyte (SLE-H) consisting of two different-sized ion conductors is prepared. Due to its higher packing density, SLE-H exhibits improved ionic conductivity. During Li plating/stripping, larger nanoparticles serve as physical barricades for dendrite growth, while smaller nanoparticles facilitate better contact with Li. Consequently, SLE-H demonstrates superior dendrite suppressing capability.


Increased training loads do not magnify cancellous bone gains with rodent jump resistance exercise.
This study sought to elucidate the effects of a low- and high-load jump resistance exercise (RE) training protocol on cancellous bone of the proximal tibia metaphysis (PTM) and femoral neck (FN). Sprague-Dawley rats (male, 6 mo old) were randomly assigned to high-load RE (HRE; n = 16), low-load RE (LRE; n = 15), or sedentary cage control (CC; n = 11) groups. Animals in the HRE and LRE groups performed 15 sessions of jump RE during 5 wk of training. PTM cancellous volumetric bone mineral density (vBMD), assessed by in vivo peripheral quantitative computed tomography scans, significantly increased in both exercise groups (+9%; P < 0.001), resulting in part from 130% (HRE; P = 0.003) and 213% (LRE; P < 0.0001) greater bone formation (measured by standard histomorphometry) vs. CC. Additionally, mineralizing surface (%MS/BS) and mineral apposition rate were higher (50-90%) in HRE and LRE animals compared with controls. PTM bone microarchitecture was enhanced with LRE, resulting in greater trabecular thickness (P = 0.03) and bone volume fraction (BV/TV; P = 0.04) vs. CC. Resorption surface was reduced by nearly 50% in both exercise paradigms. Increased PTM bone mass in the LRE group translated into a 161% greater elastic modulus (P = 0.04) vs. CC. LRE and HRE increased FN vBMD (10%; P < 0.0001) and bone mineral content (∼ 20%; P < 0.0001) and resulted in significantly greater FN strength vs. CC. For the vast majority of variables, there was no difference in the cancellous bone response between the two exercise groups, although LRE resulted in significantly greater body mass accrual and bone formation response. These results suggest that jumping at minimal resistance provides a similar anabolic stimulus to cancellous bone as jumping at loads exceeding body mass.


Using a Multi-Institutional Pediatric Learning Health System to Identify Systemic Lupus Erythematosus and Lupus Nephritis: Development and Validation of Computable Phenotypes.
Performing adequately powered clinical trials in pediatric diseases, such as SLE, is challenging. Improved recruitment strategies are needed for identifying patients. Electronic health record algorithms were developed and tested to identify children with SLE both with and without lupus nephritis. We used single-center electronic health record data to develop computable phenotypes composed of diagnosis, medication, procedure, and utilization codes. These were evaluated iteratively against a manually assembled database of patients with SLE. The highest-performing phenotypes were then evaluated across institutions in PEDSnet, a national health care systems network of >6.7 million children. Reviewers blinded to case status used standardized forms to review random samples of cases (n=350) and noncases (n=350). Final algorithms consisted of both utilization and diagnostic criteria. For both, utilization criteria included two or more in-person visits with nephrology or rheumatology and ≥60 days follow-up. SLE diagnostic criteria included absence of neonatal lupus, one or more hydroxychloroquine exposures, and either three or more qualifying diagnosis codes separated by ≥30 days or one or more diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 100% (95% confidence interval [95% CI], 99 to 100), specificity was 92% (95% CI, 88 to 94), positive predictive value was 91% (95% CI, 87 to 94), and negative predictive value was 100% (95% CI, 99 to 100). Lupus nephritis diagnostic criteria included either three or more qualifying lupus nephritis diagnosis codes (or SLE codes on the same day as glomerular/kidney codes) separated by ≥30 days or one or more SLE diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 90% (95% CI, 85 to 94), specificity was 93% (95% CI, 89 to 97), positive predictive value was 94% (95% CI, 89 to 97), and negative predictive value was 90% (95% CI, 84 to 94). Algorithms identified 1508 children with SLE at PEDSnet institutions (537 with lupus nephritis), 809 of whom were seen in the past 12 months. Electronic health record-based algorithms for SLE and lupus nephritis demonstrated excellent classification accuracy across PEDSnet institutions.


Sequestration, tissue distribution and developmental transmission of cyanogenic glucosides in a specialist insect herbivore.
Considering the staggering diversity of bioactive natural products present in plants, insects are only able to sequester a small number of phytochemicals from their food plants. The mechanisms of how only some phytochemicals are sequestered and how the sequestration process takes place remains largely unknown. In this study the model system of Zygaena filipendulae (Lepidoptera) and their food plant Lotus corniculatus is used to advance the knowledge of insect sequestration. Z. filipendulae larvae are dependent on sequestration of the cyanogenic glucosides linamarin and lotaustralin from their food plant, and have a much lower fitness if reared on plants without these compounds. This study investigates the fate of the cyanogenic glucosides during ingestion, sequestration in the larvae, and in the course of insect ontogeny. To this purpose, double-labeled linamarin and lotaustralin were chemically synthesized carrying two stable isotopes, a (2)H labeled aglucone and a (13)C labeled glucose moiety. In addition, a small amount of (14)C was incorporated into the glucose residue. The isotope-labeled compounds were applied onto cyanogenic L. corniculatus leaves that were subsequently presented to the Z. filipendulae larvae. Following ingestion by the larvae, the destiny of the isotope labeled cyanogenic glucosides was monitored in different tissues of larvae and adults at selected time points, using radio-TLC and LC-MS analyses. It was shown that sequestered compounds are taken up intact, contrary to earlier hypotheses where it was suggested that the compounds would have to be hydrolyzed before transport across the gut. The uptake from the larval gut was highly stereo selective as the β-glucosides were retained while the α-glucosides were excreted and recovered in the frass. Sequestered compounds were rapidly distributed into all analyzed tissues of the larval body, partly retained throughout metamorphosis and transferred into the adult insect where they were distributed to all tissues. During subsequent mating, isotope labeled cyanogenic glucosides were transferred from the male to the female in the nuptial gift.


Involvement of CDX2 in the cross talk between TNF-α and Wnt signaling pathway in the colon cancer cell line Caco-2.
Tumor necrosis factor-α (TNF-α) is highly upregulated in inflammation and reduces the expression of the intestinal transcription factor, Caudal-related homeobox transcription factor 2 (CDX2). Wnt/β-catenin signaling is critical for intestinal cell proliferation, but a decreased CDX2 expression has influence on the Wnt signaling-related genes and progression of colorectal cancer. Although several inflammatory signaling pathways, including TNF-α, have been reported to promote Wnt/β-catenin activity and development of cancer, the underlying molecular mechanisms remain unclear. The aim was to investigate the signaling pathways involved in the TNF-α-mediated downregulation of CDX2, and its influence on Wnt/β-catenin signaling components in colon cancer cells. The expression of TNF-α and CDX2 at the invasive front were evaluated by immunohistochemical staining and showed reduced CDX2-positive cells in tumor buddings in areas with TNF-α expression in the surrounding inflammatory cells. In vitro studies revealed that TNF-α treatment showed a dose-dependent decrease of CDX2 messenger RNA (mRNA) and protein expression in Caco-2 cells. Inhibition of nuclear factor-kappaB or p38 pathways showed that these are involved in the TNF-α-dependent downregulation of CDX2. Furthermore, TNF-α-mediated downregulation of CDX2 was found to significantly decrease the mRNA levels of adenomatous polyposis coli (APC), axis inhibition protein 2 (AXIN2) and glycogen synthase kinase-3 beta (GSK3β), whereas the mRNA levels of Wnt targets were significantly elevated in TNF-α-treated Caco-2 cells. These findings were associated with reduced binding of CDX2 to promoter or enhancer regions of APC, AXIN2 and GSK3β. In conclusion, it was found that TNF-α induces the expression of Wnt signaling components through a downregulation of the CDX2 expression that might have a tumor-promoting effect on colon cancer cells.


Aluminum tolerance in maize is associated with higher MATE1 gene copy number.
Genome structure variation, including copy number variation and presence/absence variation, comprises a large extent of maize genetic diversity; however, its effect on phenotypes remains largely unexplored. Here, we describe how copy number variation underlies a rare allele that contributes to maize aluminum (Al) tolerance. Al toxicity is the primary limitation for crop production on acid soils, which make up 50% of the world's potentially arable lands. In a recombinant inbred line mapping population, copy number variation of the Al tolerance gene multidrug and toxic compound extrusion 1 (MATE1) is the basis for the quantitative trait locus of largest effect on phenotypic variation. This expansion in MATE1 copy number is associated with higher MATE1 expression, which in turn results in superior Al tolerance. The three MATE1 copies are identical and are part of a tandem triplication. Only three maize inbred lines carrying the three-copy allele were identified from maize and teosinte diversity panels, indicating that copy number variation for MATE1 is a rare, and quite likely recent, event. These maize lines with higher MATE1 copy number are also Al-tolerant, have high MATE1 expression, and originate from regions of highly acidic soils. Our findings show a role for copy number variation in the adaptation of maize to acidic soils in the tropics and suggest that genome structural changes may be a rapid evolutionary response to new environments.


[CARASIL: Identification of the clinical concept].
CARASIL (Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy) is the second known single-gene disorder directly affecting cerebral small vessels. The acronym CARASIL was proposed by Bowler and Hachinski (1994), based on its recessive inheritance and resemblance to CADASIL (R instead of D). The first CARASIL patients were most probably described in preliminary reports in 1965-66, and later in Japanese and English articles in 1969-1976. In 1985, the author and colleagues reported on another family of three brothers with strikingly similar clinical features, including not only neurological symptoms but also recurrent acute lumbago and premature alopecia, and cerebral white matter disease on CT scans, proposing that these characteristics can constitute a new systemic syndrome. According to our clinical and pathological/neuroradiological criteria, similar patients have been reported, almost exclusively from Japan, with a total reaching 50 until today. In five consanguineous families including ours, Hara et al. (2009) identified homozygous mutations in the HTRA1 gene on chromosome 10q25. Since no founder haplotype has been identified, the author and allied researchers suspect that this disorder will be found more widely. This review summarizes the historical background, epidemiology, characteristic clinical findings, neuroimaging, and clinical perspectives after the gene identification of this disorder.


Tcra gene recombination is supported by a Tcra enhancer- and CTCF-dependent chromatin hub.
Antigen receptor locus V(D)J recombination requires interactions between widely separated variable (V), diversity (D), and joining (J) gene segments, but the mechanisms that generate these interactions are not well understood. Here we assessed mechanisms that direct developmental stage-specific long-distance interactions at the Tcra/Tcrd locus. The Tcra/Tcrd locus recombines Tcrd gene segments in CD4(-)CD8(-) double-negative thymocytes and Tcra gene segments in CD4(+)CD8(+) double-positive thymocytes. Initial V(α)-to-J(α) recombination occurs within a chromosomal domain that displays a contracted conformation in both thymocyte subsets. We used chromosome conformation capture to demonstrate that the Tcra enhancer (E(α)) interacts directly with V(α) and J(α) gene segments distributed across this domain, specifically in double-positive thymocytes. Moreover, E(α) promotes interactions between these V(α) and J(α) segments that should facilitate their synapsis. We found that the CCCTC-binding factor (CTCF) binds to E(α) and to many locus promoters, biases E(α) to interact with these promoters, and is required for efficient V(α)-J(α) recombination. Our data indicate that E(α) and CTCF cooperate to create a developmentally regulated chromatin hub that supports V(α)-J(α) synapsis and recombination.


Intermediate, But Not Extended, Afternoon Naps May Preserve Cognition in Chinese Older Adults.
The association between daytime napping and cognition is not well-studied in older adults. This study aimed to examine the associations between self-reported afternoon nap duration and change in cognition after 2-year follow-up in Chinese older adults. A total of 3,037 individuals aged 60 years and older from the China Health and Retirement Longitudinal Study baseline and 2-year follow-up were included. Overall cognition was assessed by three interview-based sub-measures of orientation to time and attention, episodic memory, and visuospatial abilities. Change scores in cognition were calculated within subjects as follow-up minus baseline levels. Based on self-reported nap duration, older adults were grouped into: (i) Non-nappers (0 minutes); (ii) Short nappers (<30 minutes); (iii) Moderate nappers (30-90 minutes); and (iv) Extended nappers (>90 minutes) at baseline and follow-up. Change in cognition was significantly associated with both baseline napping and changes in napping habits from baseline to follow-up, controlling for age, gender, education, body mass index, depression, mobility, instrumental activities of daily living, nocturnal sleep duration, and cognition at baseline. Extended nappers at baseline performed significantly worse with respect to change of overall cognition from baseline to follow-up than non-nappers, short nappers, and moderate nappers. People who napped less than 90 minutes at both assessments performed significantly better from baseline to follow-up compared to non- or extended nappers at both assessments. Results suggest that afternoon naps less than 90 minutes may be beneficial for cognition in older adults, while long afternoon naps may be detrimental.


Disaster Preparedness in Philippine Nurses.
This study examined the perceived level of disaster preparedness in Philippine nurses. A descriptive, cross-sectional research design was used in this study. Two hundred nurses were invited to participate in the study, with 170 responses (105 hospital nurses and 65 community nurses) or an 85% response rate, during the months of April 2014 through July 2014. Data collection was based on interviews using a standardized instrument, the Disaster Preparedness Questionnaire. Descriptive statistics such as frequencies, means, percentages, and standard deviations were utilized to quantify the responses. Three fourths of the respondents (n = 136, 80%) indicated that they were not fully prepared to respond to disasters, while only 20% (n = 34) acknowledged that they felt they were adequately prepared. Respondents believed that they could function in the primary roles of educator (n = 107, 62.94%), caregiver (n = 104, 61.17%), and counselor (n = 82, 48.24%). More than half of the respondents (n = 98, 57.7%) were not aware of existing protocols of disaster management in the workplace. Courses taken in such areas as first aid (n = 79, 46.4%), field triage (n = 43, 25.29%), and basic cardiac life support (n = 57, 33.53%) were cited as important in preparing for disasters. Nurses in the study revealed that they were not sufficiently prepared for disasters nor were they aware of disaster management protocols in the workplace. Hospital administrators should consider the development and formulation of disaster management protocols and provide appropriate disaster nursing education and training. Nursing curricula should incorporate basic principles of disaster management into nursing courses as a framework for addressing this critical deficit.


Long-term results of additional thrombolytic therapy in patients with acute deep vein thrombosis treated with pharmacomechanical thromboaspiration: A comparative study.
This study aims to evaluate the clinical and ultrasonographic long-term results of additional thrombolytic therapy to pharmacomechanical thromboaspiration in patients with acute and subacute lower extremity deep vein thrombosis. Medical data of a total of 68 patients ( 41 males, 27 females; mean age 38 years; range, 25 to 56 years) who were admitted to our department with the diagnosis of hyperacute or acute deep vein thrombosis between January 2013 and January 2015 were retrospectively analyzed. The patients were divided into two groups: thrombectomy without thrombolytic therapy (Group 1, n=33) and thrombectomy with thrombolytic therapy (Group 2, n=35). All patients were administered Clinical Symptom Scoring and Doppler ultrasonography at one, six, and 12 months. Clinical symptom scores were higher in Group 1 at one month (p<0.001), while there was no significant difference between the groups at six months (p=0.102). Group 1 had higher scores at 12 months (p=0.043). The complete patency rates for both groups were similar at one month (p=0.181); however, the rates were higher in Group 2 at six and 12 months (p=0.019 and p=0.002, respectively). There was no significant difference in the complete patency rates between the groups at one and six months (p=0.563 and p=0.064, respectively), while these rates were higher in Group 2 at 12 months (p=0.013). In patients with acute deep vein thrombosis, the complete patency rates were found to be higher in all control Doppler ultrasonography examinations. In the treatment of both hyperacute and acute deep vein thrombosis, the addition of thrombolytic therapy to pharmacomechanical thromboaspiration improves the clinical symptoms and venous patency rates.


Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice.
Beta-secretase (BACE1) is the rate-limiting protease for the generation of the amyloid beta-peptide (Abeta) in Alzheimer disease. Mice in which the bace1 gene is inactivated are reported to be healthy. However, the presence of a homologous gene encoding BACE2 raises the possibility of compensatory mechanisms. Therefore, we have generated bace1, bace2, and double knockout mice. We report here that BACE1 mice display a complex phenotype. A variable but significant number of BACE1 offspring died in the first weeks after birth. The surviving mice remained smaller than their littermate controls and presented a hyperactive behavior. Electrophysiologically, subtle alterations in the steady-state inactivation of voltage-gated sodium channels in BACE1-deficient neurons were observed. In contrast, bace2 knockout mice displayed an overall healthy phenotype. However, a combined deficiency of BACE2 and BACE1 enhanced the bace1-/- lethality phenotype. At the biochemical level, we have confirmed that BACE1 deficiency results in an almost complete block of Abeta generation in neurons, but not in glia. As glia are 10 times more abundant in brain compared with neurons, our data indicate that BACE2 could indeed contribute to Abeta generation in the brains of Alzheimer disease and, in particular, Down syndrome patients. In conclusion, our data challenge the general idea of BACE1 as a safe drug target and call for some caution when claiming that no major side effects should be expected from blocking BACE1 activity.


Performance Measures Based on How Adults With Cancer Feel and Function: Stakeholder Recommendations and Feasibility Testing in Six Cancer Centers.
Patient-reported outcome measures (PROMs) that assess how patients feel and function have potential for evaluating quality of care. Stakeholder recommendations for PRO-based performance measures (PMs) were elicited, and feasibility testing was conducted at six cancer centers. Interviews were conducted with 124 stakeholders to determine priority symptoms and risk adjustment variables for PRO-PMs and perceived acceptability. Stakeholders included patients and advocates, caregivers, clinicians, administrators, and thought leaders. Feasibility testing was conducted in six cancer centers. Patients completed PROMs at home 5-15 days into a chemotherapy cycle. Feasibility was operationalized as ≥ 75% completed PROMs and ≥ 75% patient acceptability. Stakeholder priority PRO-PMs for systemic therapy were GI symptoms (diarrhea, constipation, nausea, vomiting), depression/anxiety, pain, insomnia, fatigue, dyspnea, physical function, and neuropathy. Recommended risk adjusters included demographics, insurance type, cancer type, comorbidities, emetic risk, and difficulty paying bills. In feasibility testing, 653 patients enrolled (approximately 110 per site), and 607 (93%) completed PROMs, which indicated high feasibility for home collection. The majority of patients (470 of 607; 77%) completed PROMs without a reminder call, and 137 (23%) of 607 completed them after a reminder call. Most patients (72%) completed PROMs through web, 17% paper, or 2% interactive voice response (automated call that verbally asked patient questions). For acceptability, > 95% of patients found PROM items to be easy to understand and complete. Clinicians, patients, and other stakeholders agree that PMs that are based on how patients feel and function would be an important addition to quality measurement. This study also shows that PRO-PMs can be feasibly captured at home during systemic therapy and are acceptable to patients. PRO-PMs may add value to the portfolio of PMs as oncology transitions from fee-for-service payment models to performance-based care that emphasizes outcome measures.