Evaluation of ameroid ring constrictors for the management of single extrahepatic portosystemic shunts in cats: 23 cases (1996-2001).
To document the signalment; history; clinical signs; clinicopathologic, diagnostic imaging, and surgical findings; perioperative complications; and long-term clinical results of ameroid ring constrictor (ARC) placement on single extrahepatic portosystemic shunts (PSS) in cats. Retrospective study. 23 cats treated with an ARC on a single extrahepatic PSS. An ARC was placed surgically around the PSS. Portal pressure was measured prior to ARC placement, with complete temporary PSS occlusion, and after ARC placement. Cats were scheduled for recheck transcolonic portal scintigraphy 8 to 10 weeks after surgery. Follow-up information was obtained by telephone interview with the owners. An ARC was successfully placed in 22 of 23 cats. Intraoperative complications, consisting of PSS hemorrhage, occurred in 2 cats. Mean (+/- SD) portal pressure (n = 15) was 6.7+/-2.9 mm Hg before PSS manipulation, 18.6+/-7.7 mm Hg with complete temporary PSS occlusion, and 6.9+/-2.7 mm Hg after ARC placement. Postoperative complications developed in 77% (17 of 22) of cats after ARC placement, and included central blindness, hyperthermia, frantic behavior, and generalized motor seizures. Perioperative mortality rate was 4.3% (1 of 23). Persistent shunting was identified in 8 of 14 cats. Overall, 75% (15 of 20) of cats had an excellent long-term outcome. Placement of an ARC on single extrahepatic PSS in cats resulted in low surgical complication and perioperative mortality rates, but most cats did have substantial postoperative complications. Persistent shunting was common, although many cats with persistent shunting were clinically normal.


Modernization of a Large Spinal Cord Injuries and Disorders Registry: The Veterans Administration Experience.
Since the 1990s, Veterans Health Administration (VHA) has maintained a registry of Veterans with Spinal Cord Injuries and Disorders (SCI/Ds) to guide clinical care, policy, and research. Historically, methods for collecting and recording data for the VHA SCI/D Registry (VSR) have required significant time, cost, and staffing to maintain, were susceptible to missing data, and caused delays in aggregation and reporting. Each subsequent data collection method was aimed at improving these issues over the last several decades. This paper describes the development and validation of a case-finding and data-capture algorithm that uses primary clinical data, including diagnoses and utilization across 9 million VHA electronic medical records, to create a comprehensive registry of living and deceased Veterans seen for SCI/D services since 2012. A multi-step process was used to develop and validate a computer algorithm to create a comprehensive registry of Veterans with SCI/D whose records are maintained in the enterprise wide VHA Corporate Data Warehouse. Chart reviews and validity checks were used to validate the accuracy of cases that were identified using the new algorithm. An initial cohort of 28,202 living and deceased Veterans with SCI/D who were enrolled in VHA care from 10/1/2012 through 9/30/2017 was validated. Tables, reports, and charts using VSR data were developed to provide operational tools to study, predict, and improve targeted management and care for Veterans with SCI/Ds. The modernized VSR includes data on diagnoses, qualifying fiscal year, recent utilization, demographics, injury, and impairment for 38,022 Veterans as of 11/2/2022. This establishes the VSR as one of the largest ongoing longitudinal SCI/D datasets in North America and provides operational reports for VHA population health management and evidence-based rehabilitation. The VSR also comprises one of the only registries for individuals with non-traumatic SCI/Ds and holds potential to advance research and treatment for multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and other motor neuron disorders with spinal cord involvement. Selected trends in VSR data indicate possible differences in the future lifelong care needs of Veterans with SCI/Ds. Future collaborative research using the VSR offers opportunities to contribute to knowledge and improve health care for people living with SCI/Ds.


Discovery of (R)-2-amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic acid and congeners as highly potent inhibitors of human arginases I and II for treatment of myocardial reperfusion injury.
Recent efforts to identify treatments for myocardial ischemia reperfusion injury have resulted in the discovery of a novel series of highly potent α,α-disubstituted amino acid-based arginase inhibitors. The lead candidate, (R)-2-amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic acid, compound 9, inhibits human arginases I and II with IC50s of 223 and 509 nM, respectively, and is active in a recombinant cellular assay overexpressing human arginase I (CHO cells). It is 28% orally bioavailable and significantly reduces the infarct size in a rat model of myocardial ischemia/reperfusion injury. Herein, we report the design, synthesis, and structure-activity relationships (SAR) for this novel series of inhibitors along with pharmacokinetic and in vivo efficacy data for compound 9 and X-ray crystallography data for selected lead compounds cocrystallized with arginases I and II.


Variation of total organic carbon content along the stream Harsit, Eastern Black Sea Basin, Turkey.
The TOC in surface waters and wastewater is an important analytical parameter describing the total content of all organic substances containing carbon. In practice, the TOC originated from natural and anthropogenic sources, and even if it is not directly responsible for dangers on human health, its determination is important for any kind of water that is used by public. The aim of this study was to determine variation of total organic carbon (TOC) and total carbon (TC) content in the stream Harsit, which courses in Eastern Black Sea Region, Turkey. Sampling was fortnightly conducted in each of the four seasons between March 2009 and February 2010. A total of 230 water samples were collected from ten sampling stations along the main branch of the stream Harsit with 143 km of length. Obtained TOC values were evaluated and used to classify the water quality of stream Harsit, according to the Turkish Water Pollution Control Regulation (TWPCR). The annual average TOC content values for the stations were found between 2.33 and 6.97 mg/L. It was seen that the TOC content have increased along the streamcourse of Harsit until the fourth station, where reaches its maximum value. The TOC content, then, has decreased and the minimum value was observed in the eighth station. The results showed that, except in winter season, maximum TOC content observed in many of the water samples were above Class I water standard indicated in TWPCR, which classifies the water resources according to the different area of uses. It was also found that TOC has a small contribution to TC and the highest TOC content in stream waters were measured in Gumushane station where direct discharge of city wastewaters and solid waste dumping to the stream were observed.


Piloting Gain and Loss-Framed PrEP and Childbearing Messaging to Promote HIV Testing in Uganda: Perspectives from Couples and Providers.
Fears of relationship dissolution and the inability to bear healthy children remain barriers to HIV testing in sub-Saharan Africa. Pre-exposure prophylaxis (PrEP) carries both clinical and symbolic benefits that counter these fears. We conducted a pilot messaging intervention through Uganda's assisted partner notification (APN) program, where providers assist HIV-positive index clients in notifying sexual partners and encourage testing. We randomized providers at three clinics to implement phone scripts over two months with (1) gain-framed or (2) loss-framed information about PrEP and childbearing; or (3) usual care. In 23 in-depth interviews with providers, index clients, and partners, five major themes emerged on intervention acceptability and feasibility: (1) value of PrEP and childbearing messaging in APN; (2) value of this messaging coming earlier in APN; (3) overall preference for gain-framed messages; (4) need to tailor timing of messaging; and (5) need for messaging outside of APN. Register data (109 index clients, 145 partners) indicated most index clients (95%) wanted their potential conception partners informed about PrEP. Preliminary trends suggest the intervention sites outperformed usual care in testing rates among potential conception partners. Messaging that highlights PrEP and safe childbearing may be a promising new communication strategy to promote HIV testing.


In vitro evaluation of osteoprotegerin in chitosan for potential bone defect applications.
The receptor activator of nuclear factor kappa-B (RANK)/RANK ligand/osteoprotegerin (OPG) system plays a critical role in bone remodelling by regulating osteoclast formation and activity. OPG has been used systemically in the treatment of bone diseases. In searching for more effective and safer treatment for bone diseases, we investigated newly formulated OPG-chitosan complexes, which is prepared as a local application for its osteogenic potential to remediate bone defects. We examined high, medium and low molecular weights of chitosan combined with OPG. The cytotoxicity of OPG in chitosan and its proliferation in vitro was evaluated using normal, human periodontal ligament (NHPL) fibroblasts in 2D and 3D cell culture. The cytotoxicity of these combinations was compared by measuring cell survival with a tetrazolium salt reduction (MTT) assay and AlamarBlue assay. The cellular morphological changes were observed under an inverted microscope. A propidium iodide and acridine orange double-staining assay was used to evaluate the morphology and quantify the viable and nonviable cells. The expression level of osteopontin and osteocalcin protein in treated normal human osteoblast cells was evaluated by using Western blot. The results demonstrated that OPG in combination with chitosan was non-toxic, and OPG combined with low molecular weight chitosan has the most significant effect on NHPL fibroblasts and stimulates proliferation of cells over the period of treatment.


Pediatric Irritable Bowel Syndrome Patient and Parental Characteristics Differ by Care Management Type.
This study evaluates whether certain patient or parental characteristics are associated with gastroenterology (GI) referral versus primary pediatrics care for pediatric irritable bowel syndrome (IBS). A retrospective clinical trial sample of patients meeting pediatric Rome III IBS criteria was assembled from a single metropolitan health care system. Baseline socioeconomic status (SES) and clinical symptom measures were gathered. Various instruments measured participant and parental psychosocial traits. Study outcomes were stratified by GI referral versus primary pediatrics care. Two separate analyses of SES measures and GI clinical symptoms and psychosocial measures identified key factors by univariate and multiple logistic regression analyses. For each analysis, identified factors were placed in unadjusted and adjusted multivariate logistic regression models to assess their impact in predicting GI referral. Of the 239 participants, 152 were referred to pediatric GI, and 87 were managed in primary pediatrics care. Of the SES and clinical symptom factors, child self-assessment of abdominal pain duration and lower percentage of people living in poverty were the strongest predictors of GI referral. Among the psychosocial measures, parental assessment of their child's functional disability was the sole predictor of GI referral. In multivariate logistic regression models, all selected factors continued to predict GI referral in each model. Socioeconomic environment, clinical symptoms, and functional disability are associated with GI referral. Future interventions designed to ameliorate the effect of these identified factors could reduce unnecessary specialty consultations and health care overutilization for IBS.


Evidence that the TRP-1 protein is unlikely to account for store-operated Ca2+ inflow in Xenopus laevis oocytes.
The role of the TRP-1 protein, an animal cell homologue of the Drosophila transient receptor potential Ca2+ channel, in store-operated Ca2+ inflow in Xenopus laevis oocytes was investigated. A strategy involving RT-PCR and 3' and 5' rapid amplification of cDNA ends (RACE) was used to confirm and extend previous knowledge of the nucleotide and predicted amino acid sequences of Xenopus TRP-1 (xTRP-1). The predicted amino acid sequence was used to prepare an anti-TRP-l polyclonal antibody which detected the endogenous oocyte xTRP-1 protein and the human TRPC-1 protein expressed in Xenopus oocytes. Ca2+ inflow (measured using fura-2) initiated by 3-deoxy-3-fluoroinositol 1,4,5-trisphosphate (InsP3F) or lysophosphatidic acid (LPA) was completely inhibited by low concentrations of lanthanides (IC50 = 0.5 microM), indicating that InsP3F and LPA principally activate store-operated Ca2+ channels (SOCs). Antisense cRNA or antisense oligodeoxynucleotides, based on different regions of the xTRP-1 cDNA sequence, when injected into Xenopus oocytes, did not inhibit InsP3F-, LPA- or thapsigargin-stimulated Ca2+ inflow. Oocytes expressing the hTRPC-1 protein, which is 96% similar to xTRP-1, exhibited no detectable enhancement of either basal or InsP3F-stimulated Ca2+ inflow and only a very small enhancement of LPA-stimulated Ca2+ in-flow compared with control oocytes. It is concluded that the endogenous xTRP-1 protein is unlikely to be responsible for Ca2+ inflow through the previously-characterised Ca2+ -specific SOCs which are found in Xenopus oocytes. It is considered that xTRP-1 is likely to be a receptor-activated non-selective cation channel such as the channel activated by maitotoxin.


Inferring cellular forces from image stacks.
Although the importance of cellular forces to a wide range of embryogenesis and disease processes is widely recognized, measuring these forces is challenging, especially in three dimensions. Here, we introduce CellFIT-3D, a force inference technique that allows tension maps for three-dimensional cellular systems to be estimated from image stacks. Like its predecessors, video force microscopy and CellFIT, this cell mechanics technique assumes boundary-specific interfacial tensions to be the primary drivers, and it constructs force-balance equations based on triple junction (TJ) dihedral angles. The technique involves image processing, segmenting of cells, grouping of cell outlines, calculation of dihedral planes, averaging along three-dimensional TJs, and matrix equation assembly and solution. The equations tend to be strongly overdetermined, allowing indistinct TJs to be ignored and solution error estimates to be determined. Application to clean and noisy synthetic data generated using Surface Evolver gave tension errors of 1.6-7%, and analyses of eight-cell murine embryos gave estimated errors smaller than the 10% uncertainty of companion aspiration experiments. Other possible areas of application include morphogenesis, cancer metastasis and tissue engineering.This article is part of the themed issue 'Systems morphodynamics: understanding the development of tissue hardware'.


Genotypic distribution and phylogenetic characterization of Enterocytozoon bieneusi in diarrheic chickens and pigs in multiple cities, China: potential zoonotic transmission.
This study investigated diarrheic broiler and layer chickens (<50 days; n=14) and pigs of three age groups (preweaned <30 days, weaned ≈30 to 60 days, and growing >60 days; n=64) for E. bieneusi genotypes in northeast China and evaluated the potential roles of chickens and pigs in zoonotic transmission of microsporidiosis. Two 45-day-old layer chickens in city Jixi, Heilongjiang province and one 23-day-old broiler chicken in city Songyuan, Jilin province were identified to harbor a human-pathogenic E. bieneusi genotype Henan-IV and a new genotype named CC-1, respectively, by nested PCR and sequence analysis of the ribosomal internal transcribed spacer (ITS). Eleven of 64 (17.2%) duodenal mucosal specimens from pigs in city Tianjin, city Tongliao of Inner Mongolia, cities Jilin and Songyuan of Jilin province, and cities Daqing, Harbin, and Suihua of Heilongjiang province, were positive for E. bieneusi, with the infection rates of weaned pigs (35%, 7/20) significantly higher than preweaned ones (3.6%, 1/28; P<0.05). Nucleotide sequences of the ITS were obtained from 6 pig specimens, belonging to 3 known genotypes CHN7, EbpC, and Henan-IV. That the previous reports have described the occurrence of genotypes EbpC and Henan-IV in humans and EbpC in wastewater in central China and the clustering of genotypes CC-1 and CHN7 into a major phylogenetic group of E. bieneusi genotypes with zoonotic potential indicated that chickens and pigs could be potential sources of human micorsporidiosis. To our knowledge, this is the first report describing the existence of zoonotic E. bieneusi genotypes in diarrheic chickens.


Validity and reliability of the Turkish Migraine Disability Assessment (MIDAS) questionnaire.
The aim of this study is to assess the comprehensibility, internal consistency, patient-physician reliability, test-retest reliability, and validity of Turkish version of Migraine Disability Assessment (MIDAS) questionnaire in patients with headache. MIDAS questionnaire has been developed by Stewart et al and shown to be reliable and valid to determine the degree of disability caused by migraine. This study was designed as a national multicenter study to demonstrate the reliability and validity of Turkish version of MIDAS questionnaire. Patients applying to 17 Neurology Clinics in Turkey were evaluated at the baseline (visit 1), week 4 (visit 2), and week 12 (visit 3) visits in terms of disease severity and comprehensibility, internal consistency, test-retest reliability, and validity of MIDAS. Since the severity of the disease has been found to change significantly at visit 2 compared to visit 1, test-retest reliability was assessed using the MIDAS scores of a subgroup of patients whose disease severity remained unchanged (up to +/-3 days difference in the number of days with headache between visits 1 and 2). A total of 306 patients (86.2% female, mean age: 35.0 +/- 9.8 years) were enrolled into the study. A total of 65.7%, 77.5%, 82.0% of patients reported that "they had fully understood the MIDAS questionnaire" in visits 1, 2, and 3, respectively. A highly positive correlation was found between physician and patient and the applied total MIDAS scores in all three visits (Spearman correlation coefficients were R= 0.87, 0.83, and 0.90, respectively, P <.001). Internal consistency of MIDAS was assessed using Cronbach's alpha and was found at acceptable (>0.7) or excellent (>0.8) levels in both patient and physician applied MIDAS scores, respectively. Total MIDAS score showed good test-retest reliability (R= 0.68). Both the number of days with headache and the total MIDAS scores were positively correlated at all visits with correlation coefficients between 0.47 and 0.63. There was also a moderate degree of correlation (R= 0.54) between the total MIDAS score at week 12 and the number of days with headache at visit 2 + visit 3, which quantify headache-related disability over a 3-month period similar to MIDAS questionnaire. These findings demonstrated that the Turkish translation is equivalent to the English version of MIDAS in terms of internal consistency, test-retest reliability, and validity. Physicians can reliably use the Turkish translation of the MIDAS questionnaire in defining the severity of illness and its treatment strategy when applied as a self-administered report by migraine patients themselves.


Lactose intolerance genetic testing: is it useful as routine screening? Results on 1426 south-central Italy patients.
Adult-type hypolactasia is a widespread condition throughout the world, causing lactose malabsorption. Several studies suggested that the identification of C/T-13910 and G/A-22018 mutations, located upstream the gene encoding the lactase-phlorizin hydrolase (LPH), is a useful tool for the differential diagnosis of hypolactasia. We evaluated the frequencies of C/T-13910 and G/A-22018 variants in a central-south Italian population and the usefulness of lactase deficiency genetic testing in the clinic practice. The genomic DNA of 1426 patients and 1000 healthy controls from central-south Italy was isolated from peripheral whole blood and genotyped for the C/T-13910 and G/A-22018 polymorphisms by high-resolution melting analysis (HRMA) and sequencing. The frequencies of genotypes in the 1426 patients analysed were as follows: 1077 CC/GG (75.5%), 287 CT/GA (20.1%), 24 TT/AA (1.7%), 38 CC/GA (2.7%). Only 64 out of 1426 (4.5%) performed also L-BHT test, 29 of which were negative for L-BHT also in presence of different genotypes. Among the 35 individuals with L-BHT positive, 34 were CC/GG and only one CT/GA. Although lactose genetic test is a good predictor of persistence/non-persistence lactase in specific population, its use in the central-south Italy population should be limited given the high prevalence of the CCGG diplotype in normal individuals.


[Effect of eleutherococcus on short-term memory and visual perception in healthy humans].
Acute administration of a liquid eleutherococcus extract significantly improves short-term memory in healthy humans. The expression of this action depends on the daytime and psychophysiological peculiarities of the volunteers. Administration of the preparation also changes light perception by increasing retinal sensitivity. This effect was more pronounced in humans with weak type of high nervous activity in evening hours.


Staphylococcal phosphoenolpyruvate-dependent phosphotransferase system--two highly similar glucose permeases in Staphylococcus carnosus with different glucoside specificity: protein engineering in vivo?
Previous sequence analysis of the glucose-specific PTS gene locus from Staphylococcus carnosus revealed the unexpected finding of two adjacent, highly similar ORFs, glcA and glcB, each encoding a glucose-specific membrane permease EIICBA(Glc). glcA and glcB show 73% identity at the nucleotide level and glcB is located 131 bp downstream from glcA. Each of the genes is flanked by putative regulatory elements such as a termination stem-loop, promoter and ribosome-binding site, suggesting independent regulation. The finding of putative cis-active operator sequences, CRE (catabolite-responsive elements) suggests additional regulation by carbon catabolite repression. As described previously by the authors, both genes can be expressed in Escherichia coli under control of their own promoters. Two putative promoters are located upstream of glcA, and both were found to initiate transcription in E. coli. Although the two permeases EIICBA(Glc)1 and EIICBA(Glc)2 show 69% identity at the protein level, and despite the common primary substrate glucose, they have different specificities towards glucosides as substrate. EIICBA(Glc)1 phosphorylates glucose in a PEP-dependent reaction with a Km of 12 microM; the reaction can be inhibited by 2-deoxyglucose and methyl beta-D-glucoside. EIICBA(Glc)2 phosphorylates glucose with a Km of 19 microM and this reaction is inhibited by methyl alpha-D-glucoside, methyl beta-D-glucoside, p-nitrophenyl alpha-D-glucoside, o-nitrophenyl beta-D-glucoside and salicin, but unlike other glucose permeases, including EIICBA(Glc)1, not by 2-deoxyglucose. Natural mono- or disaccharides, such as mannose or N-acetylglucosamine, that are transported by other glucose transporters are not phosphorylated by either EIICBA(Glc)1 nor EIICBA(Glc)2, indicating a high specificity for glucose. Together, these findings support the suggestion of evolutionary development of different members of a protein family, by gene duplication and subsequent differentiation. C-terminal fusion of a histidine hexapeptide to both gene products did not affect the activity of the enzymes and allowed their purification by Ni2+-NTA affinity chromatography after expression in a ptsG (EIICB(Glc)) deletion mutant of E. coli. Upstream of glcA, the 3' end of a further ORF encoding 138 amino acid residues of a putative antiterminator of the BglG family was found, as well as a putative target DNA sequence (RAT), which indicates a further regulation by glucose specific antitermination.


Association of relapse-linked ARID5B single nucleotide polymorphisms with drug resistance in B-cell precursor acute lymphoblastic leukemia cell lines.
The genetic variants of the ARID5B gene have recently been reported to be associated with disease susceptibility and treatment outcome in childhood acute lymphoblastic leukemia (ALL). However, few studies have explored the association of ARID5B with sensitivities to chemotherapeutic agents. We genotyped susceptibility-linked rs7923074 and rs10821936 as well as relapse-linked rs4948488, rs2893881, and rs6479778 of ARDI5B by direct sequencing of polymerase chain reaction (PCR) products in 72 B-cell precursor-ALL (BCP-ALL) cell lines established from Japanese patients. We also quantified their ARID5B expression levels by real-time reverse transcription PCR, and determined their 50% inhibitory concentration (IC50) values by alamarBlue assays in nine representative chemotherapeutic agents used for ALL treatment. No significant associations were observed in genotypes of the susceptibility-linked single nucleotide polymorphisms (SNPs) and the relapsed-linked SNPs with ARID5B gene expression levels. Of note, IC50 values of vincristine (VCR) (median IC50: 39.6 ng/ml) in 12 cell lines with homozygous genotype of risk allele (C) in the relapse-linked rs4948488 were significantly higher (p = 0.031 in Mann-Whitney U test) than those (1.04 ng/ml) in 60 cell lines with heterozygous or homozygous genotypes of the non-risk allele (T). Furthermore, the IC50 values of mafosfamide [Maf; active metabolite of cyclophosphamide (CY)] and cytarabine (AraC) tended to be associated with the genotype of rs4948488. Similar associations were observed in genotypes of the relapse-linked rs2893881 and rs6479778, but not in those of the susceptibility-linked rs7923074 and rs10821936. In addition, the IC50 values of methotrexate (MTX) were significantly higher (p = 0.023) in 36 cell lines with lower ARID5B gene expression (median IC50: 37.1 ng/ml) than those in the other 36 cell lines with higher expression (16.9 ng/ml). These observations in 72 BCP-ALL cell lines suggested that the risk allele of the relapse-linked SNPs of ARID5B may be involved in a higher relapse rate because of resistance to chemotherapeutic agents such as VCR, CY, and AraC. In addition, lower ARID5B gene expression may be associated with MTX resistance.


Suppression among alleles encoding nucleotide-binding-leucine-rich repeat resistance proteins interferes with resistance in F1 hybrid and allele-pyramided wheat plants.
The development of high-yielding varieties with broad-spectrum durable disease resistance is the ultimate goal of crop breeding. In plants, immune receptors of the nucleotide-binding-leucine-rich repeat (NB-LRR) class mediate race-specific resistance against pathogen attack. When employed in agriculture this type of resistance is often rapidly overcome by newly adapted pathogen races. The stacking of different resistance genes or alleles in F1 hybrids or in pyramided lines is a promising strategy for achieving more durable resistance. Here, we identify a molecular mechanism which can negatively interfere with the allele-pyramiding approach. We show that pairwise combinations of different alleles of the powdery mildew resistance gene Pm3 in F1 hybrids and stacked transgenic wheat lines can result in suppression of Pm3-based resistance. This effect is independent of the genetic background and solely dependent on the Pm3 alleles. Suppression occurs at the post-translational level, as levels of RNA and protein in the suppressed alleles are unaffected. Using a transient expression system in Nicotiana benthamiana, the LRR domain was identified as the domain conferring suppression. The results of this study suggest that the expression of closely related NB-LRR resistance genes or alleles in the same genotype can lead to dominant-negative interactions. These findings provide a molecular explanation for the frequently observed ineffectiveness of resistance genes introduced from the secondary gene pool into polyploid crop species and mark an important step in overcoming this limitation.


Increasing the use of anti-inflammatory agents for acute asthma in the emergency department: experience with an asthma care map.
Acute asthma is a common emergency department (ED) presentation and variation in its management is well recognized. The present study examined the use of an asthma care map (ACM) in one Canadian ED to improve adherence to acute asthma guidelines, emphasizing the use of systemic corticosteroids (SCSs) and inhaled corticosteroids (ICSs). Three time periods were studied: the 15 months before ACM introduction (PRE), the 15 months following a three-month introduction of the ACM (POST(1)) and the 18 months after POST(1) (POST(2)). Randomly selected patient charts from each period were included from patients who were 18 to 60 years of age and presented with a primary diagnosis of acute asthma. A priori criteria were established to determine the degree of completion and success of the ACM. Primary outcomes included documentation, use of SCSs in the ED, and prescription of SCSs and ICSs at ED discharge. A total of 387 patient charts were included (PRE, n=150; POST(1), n=150; POST(2), n=87). Patient characteristics in the three groups were similar; however, patients in POST(1) and POST(2) showed higher use of newer agents than those in the PRE group. Overall, more women (n=209; 54%) than men were seen; the mean age was 32.4 years. The care map was used in 67% of cases during POST(1) and 70% during POST(2). The use of peak expiratory flow (PEF) was high during the PRE, POST(1) and POST(2) periods (91%, 89% and 91%, respectively); however, documentation of other markers of severity increased in the POST periods. Use of SCSs occurred earlier (P<0.01) and more often (57% PRE, 68% POST(1) and 75% POST(2); P<0.01) in the POST(1,2) periods than the PRE period. There was a significant increase in use of SCSs on discharge (55% PRE, 66% POST(1) and 69% POST(2); P<0.05), and prescription of ICSs significantly increased (24% PRE, 45% POST(1) and 61% POST(2); P<0.001) in the POST(1,2) periods. Discharge without any corticosteroids decreased over the three periods (32% PRE, 21% POST(1) and 17% POST(2); P<0.05). The length of stay in the ED increased over the study periods (181 min PRE, 209 min POST(1) and 265 min POST(2); P<0.01) and admissions were infrequent (9% PRE, 13% POST(1) and 6% POST(2); P=0.50). The present study provides evidence that the standardized ED ACM was widely accepted, improved chart documentation, improved some aspects of ED care and increased prescribing of discharge preventive medications.


Statistical significance of communities in networks.
Nodes in real-world networks are usually organized in local modules. These groups, called communities, are intuitively defined as subgraphs with a larger density of internal connections than of external links. In this work, we define a measure aimed at quantifying the statistical significance of single communities. Extreme and order statistics are used to predict the statistics associated with individual clusters in random graphs. These distributions allows us to define one community significance as the probability that a generic clustering algorithm finds such a group in a random graph. The method is successfully applied in the case of real-world networks for the evaluation of the significance of their communities.


Year effects drive beta diversity, but unevenly across plant community types.
Year of establishment can be a critical driver of plant communities with the establishment stage of community development particularly susceptible to factors including ambient rain, temperature, and other temporally variable drivers (e.g., seed and seedling predators). However, while year effects have been shown to drive community structure at local (patch) scales, it is yet unexplored how these within-patch effects scale up to drive landscape-level patterns of biodiversity. These dynamics are likely to be critical but are overlooked in many systems including those with high-frequency disturbance regimes or active management. Here we leveraged a series of field-based grassland mesocosms established identically at three sites across 5 years, and each monitored for 4-8 years. We compared the strength of these temporal and spatial drivers (year effects and site effects) on consequent patterns of spatial and temporal variability (beta diversity and turnover) between plots seeded with native perennial species versus those seeded with nonnative annual species. The composition of plots seeded with perennial species showed strong effects of planting year and consequently exhibited higher beta diversity within sites (across mesocosms established in five different years within sites), while plots seeded with annual species had higher between-site variation but low beta diversity within sites. Plots with annual species were also more temporally variable than plots with perennial species. These findings have important implications for our understanding of key drivers of biodiversity across landscapes. Specifically, we showed that variable trajectories in community composition generated by site and year effects during establishment can promote beta diversity across landscapes dominated by perennial species, but are considerably less impactful in annual-dominated systems. These findings further our understanding of the importance of assembly dynamics on landscape-scale patterns of diversity, and have important management implications for restoration efforts.


Activated phosphoinositide 3-kinase/AKT signaling confers resistance to trastuzumab but not lapatinib.
Trastuzumab and lapatinib provide clinical benefit to women with human epidermal growth factor receptor 2 (HER)-positive breast cancer. However, not all patients whose tumors contain the HER2 alteration respond. Consequently, there is an urgent need to identify new predictive factors for these agents. The aim of this study was to investigate the role of receptor tyrosine kinase signaling and phosphoinositide 3-kinase (PI3K)/AKT pathway activation in conferring resistance to trastuzumab and lapatinib. To address this question, we evaluated response to trastuzumab and lapatinib in a panel of 18 HER2-amplified cell lines, using both two- and three-dimensional culture. The SUM-225, HCC-1419, HCC-1954, UACC-893, HCC-1569, UACC-732, JIMT-1, and MDA-453 cell lines were found to be innately resistant to trastuzumab, whereas the MDA-361, MDA-453, HCC-1569, UACC-732, JIMT-1, HCC-202, and UACC-893 cells are innately lapatinib resistant. Lapatinib was active in de novo (SUM-225, HCC-1419, and HCC-1954) and in a BT-474 cell line with acquired resistance to trastuzumab. In these cells, trastuzumab had little effect on AKT phosphorylation, whereas lapatinib retained activity through the dephosphorylation of AKT. Increased phosphorylation of HER2, epidermal growth factor receptor, HER3, and insulin-like growth factor IR correlated with response to lapatinib but not trastuzumab. Loss of PTEN or the presence of activating mutations in PI3K marked resistance to trastuzumab, but lapatinib response was independent of these factors. Thus, increased activation of the PI3K/AKT pathway correlates with resistance to trastuzumab, which can be overcome by lapatinib. In conclusion, pharmacologic targeting of the PI3K/AKT pathway may provide benefit to HER2-positive breast cancer patients who are resistant to trastuzumab therapy.


Scalable synthesis of a biocompatible, transparent and superparamagnetic photoresist for microdevice fabrication.
The functionalization of photoresists with colloids has enabled the development of novel active and passive components for microfabricated devices. Incorporation of colloidal particles often results in undesirable reductions in photolithographic fidelity and device transparency. We present a novel photoresist composite incorporating poly(methyl methacrylate-co-methacrylic acid) (PMMA/MMA), the epoxy resin 1002F and colloidal maghemite nanoparticles to produce a stable, transparent and biocompatible photoresist. The composite photoresist was prepared in a scalable fashion in batches up to 1 kg with the particles remaining dispersed during room-temperature storage for at least 6 months. Following photolithography to form films, the nanoparticle size remained well below that of visible-light wavelengths as demonstrated by electron microscopy. Structures fabricated from the photoresist by conventional photolithography displayed aspect ratios greater than ten. When grown on the photoresist, the metabolic rate of HeLa cells was unchanged relative to cells grown on glass. Primary murine mesenchymal stem cells also displayed a normal morphology on the resist surface. The ability to manipulate microstructures formed from the composite was demonstrated by magnetically collecting clonal colonies of HeLa cells from a micropallet array. The transparency, biocompatibility, scalable synthesis and superparamagnetic properties of the novel composite address key limitations of existing magnetic composites.


Strategies to Improve Patient Engagement in Young Kidney Transplant Recipients: A Review.
Young adult and adolescent kidney transplant recipients have shorter graft survival than older and younger recipients. Although multifactorial, the tendency toward premature graft loss in young kidney transplant recipients has often been attributed to medication nonadherence and the transition from pediatric to adult care. Multiple interventions for medication nonadherence in kidney transplant recipients have been studied. Potential preventative interventions include pre-transplant screening, transition and young adult clinics, technologies such as reminders or mobile applications, and simplification of the post-transplant medication regimen. There are also recent advances in monitoring interventions for nonadherence in transplant recipients, including electronic monitoring devices such as wireless pill bottles and the Ingestible Sensor System, which incorporates ingestible microsensors into medications. Treatment interventions for medication nonadherence include cognitive behavioral programs, behavioral contracts, and screening and treatment for depression. Several of the interventions reviewed are currently available to providers caring for young kidney transplant recipients, without any complex programmatic changes. Further research in all of these areas would be of great value.


Neutrino Intensity Interferometry: Measuring Protoneutron Star Radii During Core-Collapse Supernovae.
Intensity interferometry is a technique that has been used to measure the size of sources ranging from the quark-gluon plasma formed in heavy ion collisions to the radii of stars. We investigate using the same technique to measure protoneutron star (PNS) radii with the neutrino signal received from a core-collapse supernovae. Using a full wave-packet analysis, including the neutrino mass for the first time, we derive criteria where the effect can be expected to provide the desired signal, and find that neutrinos from the next Galactic supernova should contain extractable PNS radius information.


A 28-day oral dose toxicity study enhanced to detect endocrine effects of a purified technical pentabromodiphenyl ether (pentaBDE) mixture in Wistar rats.
A 28-day subacute oral toxicity study was performed in Wistar rats with a purified preparation of the commercial pentabromodiphenyl ether (pentaBDE), DE-71. The applied OECD407 protocol was enhanced for endocrine and immune parameters, and to enable benchmark dose analysis. A vehicle control group and 7 dose groups were included, which received 0.27, 0.82, 2.47, 7.4, 22.2, 66.7 or 200 mg pentaBDE/kg bw/d (mkd). The liver appeared to be a key target organ, showing a marked increase of weight and centrilobular hepatocellular hypertrophy, probably due to the observed induction of P450 enzymes, notably CYP1A and CYP2B. A marked decrease of circulating total thyroxine (TT4) and an increase of plasma cholesterol were probably secondary to the liver effects. Furthermore, dose-dependently decreased weight of epididymis, seminal vesicles, and prostate, as well as sperm head deformities in males, and induction of CYP17 activity in adrenals in females were observed, all possibly related to anti-androgenic activity. Finally, we observed a substantial increase of large unstained cells in the blood and a decrease of apolar retinoids in the liver. All these effects had benchmark doses at the lower confidence bound (BMDL) in the low- or mid-dose range, but particular sensitive, potentially adverse effects were TT4 decrease (BMDLs 1.1 in males and 1.8 mkd in females), and decrease of hepatic apolar retinoids (BMDLs 0.5 mkd in males and 2.3 mkd in females). These results contribute to refinement of the hazard identification of pentaBDE and improved risk assessment of human exposure to this industrial chemical and environmental pollutant.


Differences in treatment of stage I colorectal cancers: a population-based study of colorectal cancers detected within and outside of a screening program.
Screen-detected colorectal cancers (CRCs) are often treated less invasively than stage-matched non-screen-detected CRCs, but the reasons for this are not fully understood. This study evaluated the treatment of stage I CRCs detected within and outside of the screening program in the Netherlands. METHODS : Data from the Netherlands Cancer Registry for all stage I CRCs diagnosed between January 1, 2008 and December 31, 2020 were analyzed, comparing patient, tumor, and treatment characteristics of screen-detected and non-screen-detected stage I CRCs. Multivariable logistic regression was used to assess the association between treatment (local excision only vs. surgical oncologic resection) and patient and tumor characteristics, stratified for T stage and tumor location. Screen-detected stage I CRCs were relatively more often T1 than T2 compared with non-screen-detected stage I CRCs (66.9 % vs. 53.3 %; P < 0.001). When only T1 tumors were considered, both screen-detected colon and rectal cancers were more often treated with local excision only than non-screen-detected T1 cancers (odds ratio [OR] 2.19, 95 %CI 1.93-2.49; and OR 1.29, 95 %CI 1.05-1.59, respectively), adjusted for sex, tumor location, lymphovascular invasion (LVI) status, and tumor differentiation. CONCLUSIONS : Less invasive treatment of screen-detected stage I CRC is partly explained by the higher rate of T1 cancers compared with non-screen-detected stage I CRCs. T1 stage I screen-detected CRCs were also more likely to undergo less invasive treatment than non-screen-detected CRCs, adjusted for risk factors such as LVI and tumor differentiation. Future research should investigate whether the choice of local excision was related to unidentified cancer-related factors or the expertise of the endoscopists.


Fostering Diversity, Equity, Inclusion, and Belonging Through the Lens of Gratitude.
Diversity, equity, inclusion, and belonging is the work of leaders. The opportunity to embrace individuality and grow collectively is something to be appreciated. The work requires leadership at all levels and starts from within. Having the courage to lean into discomfort that comes with the work reaps great rewards. Assessing your organization and applying learnings is the start to culture change. This is only the start, this work is ongoing, and it is with gratitude we should embrace to opportunity for inclusion. We as individuals and teams will benefit as well as those we serve.


Oral glucose solution as pain relief in newborns: results of a clinical trial.
It was long believed that newborns could not experience pain. As it is now documented that newborns have all the necessary systems to perceive pain, pain management can no longer be ignored. The objective of this study is to investigate which concentration of glucose is most effective in reducing pain for venipuncture in the newborn. This double-blind clinical trial of 304 newborns was conducted on a maternity and neonatal ward (neonatal medium intensive care unit). During at least 1 month, one of the four selected solutions (10, 20, 30% glucose, and placebo) was administered orally, 2 minutes before the venipuncture was performed. The pain from the skin puncture was scored using a validated pain scale (the "Leuven Pain Scale"). This study showed a significantly lower average pain score in the 30 percent glucose group (3.99) when compared with the placebo group (8.43). The average pain scores in the 20 percent glucose group (5.26) and the 10 percent glucose group (5.92) were also significantly lower than those in the placebo group. Oral administration of 2 mL of 30 percent glucose 2 minutes before the venipuncture provides the most effective pain reduction in newborns.


Cancer recurrence and mortality after pediatric heart transplantation for anthracycline cardiomyopathy: A report from the Pediatric Heart Transplant Study (PHTS) group.
We aimed to determine whether malignancy after pediatric HTx for ACM affects overall post-HTx survival. Patients <18y listed for HTx for ACM in the PHTS database between 1993 and 2014 were compared to those with DCM. A 2:1 matched DCM cohort was also compared. Wait-list and post-HTx survival, along with freedom from common HTx complications, were compared. Eighty subjects were listed due to ACM, whereas 1985 were listed for DCM. Although wait-list survival was higher in the ACM group, post-HTx survival was lower for the ACM cohort. Neither difference persisted in the matched cohort analysis. Primary cause of death in the ACM group was infection, which was higher than the DCM group. Malignancy rates were not different. All ACM malignancies were due to PTLD without primary cancer recurrence or SMN. Long-term graft survival after pediatric HTx for ACM is no different than for matched DCM peers, nor is there an increased risk of any malignancy. However, risk of infection and death from infection after HTx are higher in the ACM group. Further studies are needed to assess the effects of prior chemotherapy on susceptibility to infection in this group.


The impact of Lewis acid variation on reactions with di-tert-butyl diazo diesters.
Reactions of (tBuO2CN)2 with Lewis acids and FLPs have previously been shown to prompt the formation of diazene compounds. In this work, we show that the reaction of (tBuO2CN)2 with 9-BBN leads to a bicyclic heterocyclic product (tBuOCO(BBN)CN)21. In contrast, the reactions of (tBuO2CN)2 with BF3 or [Et3Si][B(C6F5)4] lead to the isolation of [tBuNHNH2tBu][BF4] 2 and [tBuN(H)NtBu][B(C6F5)4] 3, respectively. The mechanism for the formation of 2 is probed computationally, demonstrating that steric and electronic considerations of the Lewis acid impact the reaction pathway.


[The image in qualitative research in health].
This paper explores the use of the image as a methodological instrument in qualitative research in health. It is divided into two parts. The first part, which is theoretical in perspective, deals with aspects of anthropological fieldwork in which different views interact in the interpretation, either in the speech of the social actor or in the image that is produced. The second part describes two empirical studies on the image as a methodological instrument to obtain qualitative data, presenting research with images recorded on DVD and photographs of garbage pickers and garbage collectors, respectively. The conclusion reached is that the image can be used both as a complementary example, and as an instrument in qualitative research. Participant observation and interviews can be supplemented with the image but the image itself generates an accumulation of information, stimulating the viewer's ability to comprehend.


Evidence Against a Role for Protein Kinase C in the Inhibition of the Calcium-activated Potassium Current IAHP by Muscarinic Stimulants in Rat Hippocampal Neurons.
The possible role of protein kinase C activation in the inhibitory action of cholinergic transmitters on the slow Ca-dependent afterhyperpolarizing current (IAHP) in hippocampal CA3 pyramidal neurons was investigated using hippocampal slice cultures. IAHP was inhibited reversibly by methacholine (100 - 600 nM) and irreversibly by the protein kinase C activator, phorbol-12,13-dibutyrate (PDBu, 10 nM to 1 microM). The inhibitory action of PDBu was antagonized by prior (15 - 60 min) exposure to staurosporin (1 microM). In contrast, the inhibitory effect of methacholine on IAHP was not reduced after up to 3 h of exposure to this compound. In addition, methacholine produced a reversible inward current at the holding potential, which was augmented by staurosporin. However, prior exposure to PDBu reduced the effect of methacholine on IAHP and occluded the methacholine-induced inward current. This effect of PDBu was also observed in the presence of staurosporin, suggesting that it might be exerted through a protein kinase C-independent pathway. Noradrenalin (2 - 5 microM) and 8-bromo cyclic adenosine 3',5'monophosphate (8-Br-cAMP, 1 mM) also produced a reversible block of IAHP. Their action was antagonized by staurosporin, probably via its effect on protein kinase A. Thus the present experiments suggest that the action of muscarinic agonists on IAHP cannot be explained by an effect on protein kinase C, but support a role for protein kinase A in mediating the action of noradrenalin.


Sleep disorders and medical conditions in women. Proceedings of the Women & Sleep Workshop, National Sleep Foundation, Washington, DC, March 5-6, 2007.
Sleep disorders affect women differently than they affect men and may have different manifestations and prevalences. With regard to obstructive sleep apnea (OSA), variations in symptoms may cause misdiagnoses and delay of appropriate treatment. The prevalence of OSA appears to increase markedly after the time of menopause. Although OSA as defined by the numbers of apneas/hypopneas may be less severe in women, its consequences are similar and perhaps worse. Therapeutic issues related to gender should be factored into the management of OSA. The prevalence of insomnia is significantly greater in women than in men throughout most of the life span. The ratio of insomnia in women to men is approximately 1.4:1.0, but the difference is minimal before puberty and increases steadily with age. Although much of the higher prevalence of insomnia in women may be attributable to the hormonal or psychological changes associated with major life transitions, some of the gender differences may result from the higher prevalence of depression and pain in women. Insomnia's negative impact on quality of life is important to address in women, given the high relative prevalence of insomnia as well as the comorbid disorders in this population. Gender differences in etiology and symptom manifestation in narcolepsy remain understudied in humans. There is little available scientific information to evaluate the clinical significance and specific consequences of the diagnosis of narcolepsy in women. Restless legs syndrome (RLS) is characterized by an urge to move the legs or other limbs during periods of rest or inactivity and may affect as much as 10% of the population. This condition is more likely to afflict women than men, and its risk is increased by pregnancy. Although RLS is associated with impaired quality of life, highly effective treatment is available.


[Development of embryonal brain synapses in the normal state and in maternal alcoholism].
Electron microscopy was used to study embryonal brains (n-10) of 7-12-week gestation from mothers abusing alcohol at the time of medical abortion. Control group consisted of 20 embryos from healthy women. The study group demonstrated delayed formation of synaptic structures, a great number of extrasynaptic contacts, sings of clear-type degeneration of some mature synapses.


How to Estimate Optimal Malaria Readiness Indicators at Health-District Level: Findings from the Burkina Faso Service Availability and Readiness Assessment (SARA) Data.
One of the major contributors of malaria-related deaths in Sub-Saharan African countries is the limited accessibility to quality care. In these countries, malaria control activities are implemented at the health-district level (operational entity of the national health system), while malaria readiness indicators are regionally representative. This study provides an approach for estimating health district-level malaria readiness indicators from survey data designed to provide regionally representative estimates. A binomial-hierarchical Bayesian spatial prediction method was applied to Burkina Faso Service Availability and Readiness Assessment (SARA) survey data to provide estimates of essential equipment availability and readiness for malaria care. Predicted values of each indicator were adjusted by the type of health facility, location, and population density. Then, a health district composite readiness profile was built via hierarchical ascendant classification. All surveyed health-facilities were mandated by the Ministry of Health to manage malaria cases. The spatial distribution of essential equipment and malaria readiness was heterogeneous. Around 62.9% of health districts had a high level of readiness to provide malaria care and prevention during pregnancy. Low-performance scores for managing malaria cases were found in big cities. Health districts with low coverage for both first-line antimalarial drugs and rapid diagnostic tests were Baskuy, Bogodogo, Boulmiougou, Nongr-Massoum, Sig-Nonghin, Dafra, and Do. We provide health district estimates and reveal gaps in basic equipment and malaria management resources in some districts that need to be filled. By providing local-scale estimates, this approach could be replicated for other types of indicators to inform decision makers and health program managers and to identify priority areas.


Attachment to parents: the mediating role of inhibition of exploration and individuality on health behaviors.
This study's goal was to analyze whether the quality of university students' relationship with their parents mediated the association between mental health and physical symptoms and health behavior. Participants were 250 university students (66% female and 34% male), aged between 17 and 29 years old (M = 20.88, SD = 2.03) that answered the Father/Mother Attachment Questionnaire (FMAQ), the Physical Symptoms Scale from the Rotterdam Symptom Checklist (RSCL), the Health Behavior Questionnaire (HBQ), and the Hospital Anxiety and Depression Scale (HADS). The results showed that the indirect effect of physical symptoms on health behavior was significantly mediated by the father's and mother's inhibition of exploration and individuality (IEI). Also the indirect effect of psychological distress on health behavior was significantly mediated by the father's and mother's IEI. These results suggest that young adults who had more restrictions to their individuality show worse health behaviors. Separation Anxiety and Dependence (SAD) and Quality of Emotional Bond (QEB), the other 2 attachment scales, were not mediators of the relationship between physical symptoms/psychological distress and health behavior. This study shows the importance of promoting positive parenting practices that contribute to healthier behavior choices and less risky behaviors, as well as the need for more studies that clearly identify these practices in young adult populations.


Downstaging of hepatocellular carcinoma and liver metastases from colorectal cancer by selective intra-arterial chemotherapy.
Although resection is the sole chance of cure in patients with hepatocellular carcinoma (HCC) or metastatic colorectal cancer to the liver, most patients are not candidates for surgery at the time of diagnosis. Strategies aiming at downstaging large or multifocal tumors to enable curative resection are appealing. The aim of this study was to evaluate the effects of neoadjuvant selective intra-arterial chemotherapy in noncirrhotic patients with unresectable HCC or metastatic colorectal cancer to the liver in the absence of extrahepatic disease. Selective chemotherapy was provided by using a subcutaneous pump device via a catheter placed in the gastroduodenal artery. Chemotherapy regimen included floxuridine (0.2 mg/kg/day for 14 days) in each patient with additional boluses of cisplatin and doxorubicin on day 1 of each cycle in the presence of HCC. Patients were evaluated at 3, 6, 9, and 12 months for possible curative resection. Complete follow-up was available for each patient. Twenty-eight patients with unresectable liver tumors (5 HCC and 23 metastatic colorectal cancer) were included in this study. There were no surgical complications related to pump insertion, and local chemotherapy was started within 1 week of surgery in each patient. The median follow-up in survivors was 31 months (range, 30 months to 5 years). Chemotherapy was well tolerated in 18 (64%) patients. Chemotherapy was discontinued in 4 patients because of abnormal liver function test results, and 2 of them required a biliary stent to relieve a biliary stricture. In 9 patients downstaging enabled curative resection (3 HCC, 6 colorectal metastasis). Seven of these patients were alive and tumor free at the completion of the study, with at least 2 years of follow-up. The actuarial survival rates at 3 years for HCC and colorectal metastases were 60% and 50%, respectively. About one third of patients with unresectable liver tumors can be successfully treated by neoadjuvant intra-arterial chemotherapy followed by curative resection. This strategy appears particularly promising in patients with large HCC. This approach should be investigated further.


Crohn's disease and small bowel adenocarcinoma: a population-based case-control study.
Although Crohn's disease (CD) is thought to predispose to adenocarcinomas of the small bowel, the association has not been well studied in an older population. The objective of our study was to evaluate the association of CD with small bowel cancer in a population-based case-control study. All cases of small bowel cancer in persons 67 and older in the Surveillance, Epidemiology and End Results catchment area and in the Medicare claims data base were compared with cancer-free controls residing in the same geographic area. We used multivariable logistic regression models adjusted for demographic and other factors. We identified 923 cases of small bowel cancer and 142,273 controls. Although we found a strong association between CD and small bowel cancer (OR = 12.07; 95% CI: 6.07-20.80; P < 0.001), the prevalence of CD in patients with small bowel cancer was low (1.6%). Although CD is a significant risk factor for small bowel cancers among individuals older than 67, the absolute risk is small. Older individuals with CD can be reassured that although there is an association between CD and small bowel cancer, the absolute risk remains small.


Changes in the dynamics of the vertical vestibulo-ocular reflex due to linear acceleration in the frontal plane of the cat.
The vertical and horizontal components of the vestibulo-ocular reflex (VOR) were recorded in alert, restrained cats who were placed on their sides and subjected to whole-body rotations in the horizontal plane. The head was either on the axis or 45 cm eccentric from the axis rotation. During off-axis rotation there was a change in the linear force acting on the otolith organs due to the presence of a centripetal acceleration along the animal's vertical axis. Otolith forces (defined to be opposite to the centripetal acceleration) directed ventrally with respect to the animal (negative) decreased both the amplitude and time constant of the first-order approximation to the slow phase eye velocity of the vertical vestibulo-ocular reflex (VVOR). Otolith forces directed dorsally (positive) increased the amplitude and time constant. The effects were greater for the up VOR. The asymmetry in the VVOR time constant also depended on the otolith forces, being less in the presence of negative otolith forces that caused the resultant otolith force to move ventrally, towards the direction along which gravity normally acts when the animal is in the upright position. The effects of otolith forces on the up VVOR were independent of whether the animals were tested in the dark or in the light with a stationary visual surround (i.e., during visual suppression). In contrast, the changes in the time constant of the down VVOR were smaller during visual suppression. Simulations of the eye velocity storage mechanism suggest that the gain of the feedback in the storage integrator was modified by the angle between the resultant otolith force and an animal-fixed reference. This could be the animal's vertical, i.e., the direction along which gravity normally acts. For larger angles the feedback was less and the amplitude and time constant of the VVOR increased. The transformation of the otolith input was the same for both the up and down VOR, even though the final effect on the eye velocity was asymmetric (larger for up VOR) due to a separate, asymmetric gain element in the velocity storage feedback pathway.


Complete Response to Afatinib of an EGFR Exon 18 delE709_T710insD-Mutated Stage IV Lung Adenocarcinoma.
Epidermal growth factor receptor (EGFR) mutations are frequently found in patients with lung adenocarcinomas, 90% being deletions in exon 19 or point mutation in exon 21. Three generations of tyrosine kinase inhibitors (TKIs) targeting EGFR mutations are available and have changed patient prognosis but less data is available on exon 18 mutations and their sensitivity to TKI therapy. Exon 18 delE709_T710insD accounts for 0.06% (16/27,294) of all EGFR mutations and is an oncogenic driver. Several partial responses to afatinib have been described. We report the first case, to the best of our knowledge, of the complete response to afatinib of a 57-year-old patient with stage IV lung adenocarcinoma with a delE709_T710insD mutation in the EGFR gene detected by next-generation sequencing. Oral afatinib was prescribed and despite treatment interruptions and dosage tapering due to cutaneous adverse events, a complete response was achieved 12 months after treatment initiation and is currently maintained at 17 months. When EGFR mutation is suspected, complete DNA sequencing of exons 18 to 21 should be carried out and we suggest that afatinib should be the first-line treatment for exon 18 delE709_T710insD-mutated advanced lung adenocarcinomas. Rare EGFR gene mutations are not detected by standard diagnostic kits.DNA sequencing is required to diagnose rare mutations of the EGFR gene.delE709_T710insD-mutated stage IV lung adenocarcinomas respond to afatinib.


Menopausal symptoms, exercise practices, and advice received in active women: a multi-country survey of strava app users.
The study aimed to identify the prevalence of symptoms, changes in exercise levels, and exercise advice received during the menopausal transition in a large multi-country sample. Using total population sampling, 2.5 percent of female Strava app users (n = 970) from 7 countries completed an online survey between 14 February 2019 and 11 March 2019. The survey discussed menopause status (perimenopausal or postmenopausal), menopausal symptoms, changes to exercise behaviors, and advice received concerning exercise during menopause. Frequencies, chi-square statistics, and linear regressions were used to analyze data. The most commonly reported menopausal symptoms were sexual (18-83 percent) and cognitive/psychological (77-78 percent). 41 percent of women reported no change in exercise behavior since menopause began (46 percent increased and 11 percent decreased behaviors). The majority (88 percent) of women did not receive advice regarding exercise during menopause. Women who received advice were more likely to report an increase in their exercise than those not receiving advice (60 percent vs 46 percent; X2 (df 2, n = 927) = 7.1, p = .03). Exercise behaviors increased the longer it had been since the menopausal onset (X2 (df 8, n = 937) = 77.42, p < .001). The results suggested high menopausal symptom prevalence in active women and a general lack of exercise advice. More women reported higher symptom prevalence and an increase in exercise participation, the longer it had been since menopause onset. Future research should determine whether these increased exercise behaviors are being used as a coping mechanism.


Assessment of sympathetic neural activity in chronic insomnia: evidence for elevated cardiovascular risk.
Chronic insomnia affects up to 15 per cent of adults. Recent cross-sectional and prospective epidemiological studies report an association between insomnia and hypertension, including incident hypertension, yet mechanisms underlying the association remain unknown. We hypothesized that participants with chronic insomnia would have elevated sympathetic neural outflow, blunted baroreflex sensitivity, and augmented sympathetic neural and cardiovascular reactivity to stress when compared with good-sleeper controls. Twelve participants with chronic insomnia (11 women, 1 man) and 12 controls (8 women, 4 men) underwent one night of laboratory polysomnography, two weeks of at-home wrist actigraphy, and one night of controlled laboratory sleep prior to a comprehensive morning autonomic function test. The autonomic function test consisted of simultaneous recordings of muscle sympathetic nerve activity (MSNA; microneurography), beat-to-beat blood pressure (finger plethysmography), and heart rate (electrocardiogram) during a 10 min supine baseline and a 2 min cold pressor test. Baseline blood pressure, heart rate, and MSNA were not different between groups, but sympathetic baroreflex sensitivity was significantly blunted in participants with insomnia (-2.1 ± 1.0 vs. -4.3 ± 1.3 bursts/100 heartbeats/mm Hg; p < 0.001). During the cold pressor test, systolic arterial pressure reactivity (Δ21 ± 11 vs. Δ14 ± 8 mm Hg; time × group = 0.04) and total MSNA reactivity (Δ127%, 54%-208% vs. Δ52%, 30%-81%; time × group = 0.02) were augmented in chronic insomnia. Participants with chronic insomnia demonstrated impaired sympathetic baroreflex function and augmented neural cardiovascular responsiveness to stress, when compared with controls. These findings support growing evidence of cardiovascular risk and physiological hyperarousal in chronic insomnia. NCT02048878. https://clinicaltrials.gov/ct2/show/NCT02048878.


Evaluation of professional preparation in athletic training by employed, entry-level athletic trainers.
The purpose of this study was to determine the perceived adequacy of professional preparation in athletic training among employed, entry-level certified athletic trainers. Data were gathered by means of a self-reporting questionnaire designed specifically for the study. There were 277 questionnaires mailed, and 183 entry-level certified athletic trainers (66%) responded to the survey. Demographic and employment characteristics of the respondents were examined. Respondents rated their perceptions of adequacy of professional preparation and growth in several academic and clinical task areas. Entry-level athletic trainers felt more prepared in the areas of prevention of athletic injuries/illnesses, evaluation and recognition of athletic injuries/illnesses, and first aid/emergency care. They felt less prepared in the areas of rehabilitation and reconditioning, organization and administration of athletic training programs, counseling and guidance of athletes, and education of athletes. Many entry-level certified athletic trainers were not strongly impressed with the adequacy of the number of clinical hours required or the areas of clinical experiences encountered during their professional preparation programs. Respondents felt that their mentors/certified athletic trainers could have provided more leadership, guidance, and evaluation. According to this study, professional preparation programs in athletic training are adequately preparing entry-level professionals, but certain task areas need increased emphasis.


Effect of physical exercise and sleep deprivation on plasma androgen levels: modifying effect of physical fitness.
The responses of plasma testosterone (T), sex hormone-binding globulin (SHBG) binding capacity, androstenedione (A), and luteinizing hormone (LH) to 21 km of marching exercise and to sleep deprivation stress were studied in army recruits. The effect of physical fitness on the exercise responses was evaluated, cross-sectionally, by comparing the stress responses in 11 fit and 11 less fit subjects, and, longitudinally, in 11 subjects after 4 months of physical training. The submaximal marching exercise did not significantly alter the plasma hormone levels compared to the control day levels. The fit subjects had a tendency toward smaller decreases in the mean plasma T and T/SHBG ratio during both control and exercise days than the less fit subjects. After 4 months of conditioning, the mean plasma T and T/SHBG ratio tended to decrease less during both control and exercise days, which was more evident in the well-conditioned subjects. The exercise caused a decrease in mean plasma LH, especially in the less fit subjects. After sleep deprivation stress, the morning levels of plasma T, A, and LH were significantly depressed, as a result of which the normal diurnal variation of the hormones disappeared.


The lived experiences of hematology healthcare providers during and beyond the COVID-19 crisis: A qualitative study.
Amid the COVID-19 pandemic, healthcare providers (HCPs) of hematology patients face unique challenges due to the vulnerability of their patients. This study explores the lived experiences of these providers during and beyond the crisis. Twenty-one Australian HCPs caring for hematology patients completed semi-structured interviews exploring their experiences and needs during the COVID-19 pandemic, adequacy of support and information provided by healthcare organizations, impact on hematology patients, and the benefits and challenges of telehealth care. Data were analyzed using reflexive thematic analysis. Four themes were identified: (1) Managing an initial state of flux (unsettling uncertainty and fear, unique needs of hematology patients, getting on with the job together); (2) Concerns about care provision (questioning care efficacy, burden of compassion); (3) Disconnect between HCP needs and system-level responses (burnout, isolation, and poor work-life balance, broadcast fatigue, protecting mental health), and; (4) Reflecting on the future (ongoing challenges for hematology patients, higher staff turnover and heavier workloads, innovation in the healthcare field). This study sheds light on the challenges that hematology HCPs face during and beyond the COVID-19 crisis, impacting their wellbeing. Addressing these challenges is paramount for the healthcare system at large. Provider-led peer support programs may be beneficial for addressing moral distress and building resilience. Additionally, specific consideration for the ongoing vulnerability of hematology patients could have positive impacts on providers' professional satisfaction.


Ultrasonographic evaluation of disc displacement of the temporomandibular joint compared with magnetic resonance imaging.
We compared high-resolution ultrasonography with magnetic resonance imaging (MRI), as the gold standard, to evaluate lateral and anterior capsule-condyle distances to detect disc displacement of the temporomandibular joint. This study included 28 patients (19 female and 9 male; age range, 16-51 years; mean age, 32.82 years), and in total, 56 joints were assessed with ultrasonography and MRI. Measurements were obtained for anterior capsule-condyle and lateral capsule-condyle distances in both open- and closed-mouth positions with high-resolution ultrasonography. These findings were also compared with those of MRI taken as reference. Receiver operating characteristic curve analysis was performed to assess our results. We assessed sensitivities, specificities, accuracies, and positive and negative predictive values for both open- and closed-mouth positions. Diagnostic accuracy of ultrasonographic anterior capsule-condyle distance in the closed-mouth position to detect MRI-positive disc displacement (area under receiver operating characteristic curve, 0.689; P = .015) was the highest. The measurement of the distance between the most anterior point of the articular capsule and the most anterior point of the condyle can be used to assess disc displacement in diseased joints. However, it is necessary to determine the most accurate threshold value and to set cutoff values. These findings need to be confirmed by further research in a large number of patients to test the interexaminer agreement and the reproducibility of this method.


Diabetes, adult neurogenesis and brain remodeling: New insights from rodent and zebrafish models.
The prevalence of diabetes rapidly increased during the last decades in association with important changes in lifestyle. Diabetes and hyperglycemia are well-known for inducing deleterious effects on physiologic processes, increasing for instance cardiovascular diseases, nephropathy, retinopathy and foot ulceration. Interestingly, diabetes also impairs brain morphology and functions such as (1) decreased neurogenesis (proliferation, differentiation and cell survival), (2) decreased brain volumes, (3) increased blood-brain barrier leakage, (4) increased cognitive impairments, as well as (5) increased stroke incidence and worse neurologic outcomes following stroke. Importantly, diabetes is positively associated with a higher risk to develop Alzheimer disease. In this context, we aim at reviewing the impact of diabetes on neural stem cell proliferation, newborn cell differentiation and survival in a homeostatic context or following stroke. We also report the effects of hyper- and hypoglycemia on the blood-brain barrier physiology through modifications of tight junctions and transporters. Finally, we discuss the implication of diabetes on cognition and behavior.


Experimental hypersensitivity in the rabbit; effect of inhibition of antibody formation by X-radiation and nitrogen mustards on the histologic and serologic sequences, and on the behavior of serum complement, following single large injections of foreign Proteins.
X-radiation and nitrogen mustard administration inhibit the formation of precipitins for whole bovine serum and bovine serum gamma globulin in the rabbit. When specific antibody formation is inhibited by these agents, intravenous injection of a single large dose of bovine serum gamma globulin is not usually followed by the development of tissue lesions 9 to 11 days later, as occurs fairly regularly in control animals. A fall in titre of serum complement to very low levels for 3 to 5 days is closely correlated in time with the disappearance of antigen from the circulation following the intravenous injection of single large doses of bovine serum albumin and bovine serum gamma globulin. A rise in complement titre to normal levels occurs as antibodies appear in the serum. This sudden fall in complement titre is correlated with the development of characteristic lesions, and does not occur when antibody formation is inhibited. The data presented are interpreted as evidence in favor of the concept that the lesions are due to a reaction between antigen fixed in or on tissue cells and circulating antibody. The possible significance of serum complement in the pathogenesis of anaphylactic tissue lesions is discussed.


Acute fasting inhibits central caspase-1 activity reducing anxiety-like behavior and increasing novel object and object location recognition.
Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food. Immediately after fasting, caspase-1 activity was measured in brain region homogenates while activated caspase-1 was localized in the brain by immunohistochemistry. Mouse anxiety-like behavior and cognition were tested using the elevated zero maze and novel object/object location tasks, respectively. A 24h fast in mice reduced the activity of caspase-1 in whole brain and in the prefrontal cortex, amygdala, hippocampus, and hypothalamus by 35%, 25%, 40%, 40%, and 40% respectively. A 24h fast also reduced anxiety-like behavior by 40% and increased novel object and object location recognition by 21% and 31%, respectively. IL-1β protein, however, was not reduced in the brain by fasting. ICV administration of YVAD decreased caspase-1 activity in the prefrontal cortex and amygdala by 55%, respectively leading to a 64% reduction in anxiety like behavior. Importantly, when caspase-1 KO or IL1-R1 KO mice are fasted, no fasting-dependent reduction in anxiety-like behavior was observed. Results indicate that fasting decrease anxiety-like behavior and improves memory by a mechanism tied to reducing caspase-1 activity throughout the brain.


Longitudinal [18]UCB-H/[18F]FDG imaging depicts complex patterns of structural and functional neuroplasticity following bilateral vestibular loss in the rat.
Neuronal lesions trigger mechanisms of structural and functional neuroplasticity, which can support recovery. However, the temporal and spatial appearance of structure-function changes and their interrelation remain unclear. The current study aimed to directly compare serial whole-brain in vivo measurements of functional plasticity (by [18F]FDG-PET) and structural synaptic plasticity (by [18F]UCB-H-PET) before and after bilateral labyrinthectomy in rats and investigate the effect of locomotor training. Complex structure-function changes were found after bilateral labyrinthectomy: in brainstem-cerebellar circuits, regional cerebral glucose metabolism (rCGM) decreased early, followed by reduced synaptic density. In the thalamus, increased [18F]UCB-H binding preceded a higher rCGM uptake. In frontal-basal ganglia loops, an increase in synaptic density was paralleled by a decrease in rCGM. In the group with locomotor training, thalamic rCGM and [18F]UCB-H binding increased following bilateral labyrinthectomy compared to the no training group. Rats with training had considerably fewer body rotations. In conclusion, combined [18F]FDG/[18F]UCB-H dual tracer imaging reveals that adaptive neuroplasticity after bilateral vestibular loss is not a uniform process but is composed of complex spatial and temporal patterns of structure-function coupling in networks for vestibular, multisensory, and motor control, which can be modulated by early physical training.


Use of hepatitis B virus vaccine in Africa: rationale and practical approaches for effective utilization.
This report considers the following questions: (1) Should hepatitis B virus (HBV) vaccine be used in Africa, if and when adequate supplies become available at an affordable cost? (2) Who should receive the vaccine and when? (3) What type of HBV vaccine should be used? Answers to these questions are suggested based on a review of available knowledge of the epidemiology of HBV infections in Africa, the role of HBV in the etiology of hepatocellular carcinoma and cirrhosis, and the utilization of various currently available and experimental HBV vaccines.


The role of genomics and biotechnology in achieving global food security for high-oleic vegetable oil.
Health related concerns for dietary 'trans-fat' in the U.S. have mediated a significant decline in the use of hydrogenated vegetable oils in edible applications. Oils having a natural abundance of oleic acid provide many functional properties that are derived from partial hydrogenation of polyunsaturated oils. However, the long term agronomic production capacity of existing high-oleic oil crops to replace hydrogenated oil ingredients is not sustainable. Although improvements are expected in processing technology, genetic modification of seed composition offers the most promising tactic to increase the overall supply of high-oleic commodity oils. Genetic enhancement of oleic acid concentration has been demonstrated experimentally in nearly every oilseed. Private companies have launched production of genetically enhanced oleic acid cultivars such as: Nexera™ Omega-9 canola and Omega-9 sunflower oils. The E. I. du Pont de Nemours and Company plans commercial production of Plenish™ high-oleic soybeans in 2012. The Monsanto Co. plans commercial production of Vistive-Gold™ low-saturated high-oleic soybeans possibly as early as 2013. These 'new' high-oleic oilseeds must not only exhibit superior oil quality but also sequentially improved yield potential. Genetic maps that help breeders identify, locate and track useful genes will facilitate accomplishment of that goal. However, a reference sequence map in soybean is the only available chromosome scale assembly of an oilseed genome. Knowledge of genome structure enables technological advances that help increase soybean yielding ability, improve crop protection against biotic stresses, and reveal alleles for genes that mediate expression of quality traits. Led by soybean, genetically enhanced high-oleic vegetable oils that now are becoming commercially available may capture greater than 40% of the domestic consumption of vegetable oil in the U.S. by 2020. This innovation in oilseed technology is a positive step toward ensuring global food security for high-oleic vegetable oils.


MicroRNA-455-3p functions as a tumor suppressor by targeting eIF4E in prostate cancer.
MicroRNAs (miRNAs) are strongly implicated in various cancers, including prostate cancer. Recently, microRNA-455-3p (miR-455-3p) has been shown to be aberrantly expressed in many tumor tissues, but its functions in tumorigenesis remain unknown. In this study, we investigated the role of miR-455-3p in prostate cancer. We found that miR-455-3p is markedly downregulated in prostate cancer cell lines and clinical tumor specimens. Gain-of-function and loss-of-function studies showed that miR-455-3p promotes prostate cancer cell growth both in vitro and in vivo. Bioinformatics analysis and Luciferase reporter assays demonstrated that miR-455-3p directly targets and suppresses eIF4E, the rate-limiting factor for cap-dependent translation, which plays important roles in the initiation and progression of prostate cancers. Further studies demonstrated that miR-455-3p inhibits cap-dependent translation and the proliferation of prostate cancer cells through targeting eIF4E. Taken together, our findings suggest that miR-455-3p functions as a tumor suppressor by directly targeting eIF4E in prostate carcinogenesis and may be used as a potential target for therapeutic intervention in prostate cancer.


Rectal nonsteroidal anti-inflammatory drugs administration is effective for the prevention of post-ERCP pancreatitis: An updated meta-analysis of randomized controlled trials.
Acute pancreatitis is one of the most common complications of endoscopic retrograde cholangiopancreatography (ERCP). Whether the prophylactic administration of rectal non-steroidal anti-inflammatory drugs (NSAIDs) peri-ERCP is effective in preventing post-ERCP pancreatitis (PEP) remains controversial. The aim of this study was to assess the effect of rectal NSAIDs on PEP. A systematic search of literature databases (Cochrane Library, PubMed, EMBASE, and Web of Science) was performed to identify eligible randomized controlled trials (RCTs). The Jadad score for assessing risk of bias was used to evaluate the quality of included studies. The primary endpoint of the study was efficacy for PEP prevention. Sub-analyses were performed to determine the risk reduction for different NSAID types, for general vs. high-risk patients, by timing of administration and for moderate to severe PEP. Twelve RCTs, including a total of 3989 patients, were identified and included in the analysis. The risk of PEP was lower in the NSAIDs group than in the placebo group (RR 0.52; 95% CI 0.43-0.64; P < 0.01). The risk of moderate to severe PEP was also lower in the NSAIDs group. (RR 0.44; 95% CI 0.28-0.69; P < 0.01). There was no difference in efficacy between rectal indomethacin and diclofenac, nor between pre-ERCP and post-ERCP administration timing of rectal NSAIDs. A single rectal dose of NSAIDs is effective in preventing PEP both in high-risk and in unselected patients, regardless of timing of administration (pre- or post-ERCP) and NSAID type (indomethacin or diclofenac).


[Studying intermediatory regulation of heart rhythm using Daphnia magna as the alternative test object].
A functional test using Daphnia magna Straus hydrobionts is proposed for studying the role of intermediatory relationships in the heart rate (HR) regulation. It is established that the M-cholinomimetic carbamylcholine increases for two hours and decreases after 24 hours the HR in D. magna. Caffeine (a nonselective antagonist of adenosine receptors) potentiates the action of carbamylcholine during the first hour and then ceases to influence the drug effect. Caffeine normalizes the HR rate D magna, which was decreased by the cholinolytic atropine and the beta-adrenolytic atenolol. The possibilities of using the proposed test for the investigation of intermediatory relationships in the HR regulation, rapid analysis of the cardiothropic action of xenobiotics, and the primary screening of drugs for the pharmacological correction of HR disturbances are discussed.


Significant Strain Dissipation via Stiff-Tough Solid Electrolyte Interphase Design for Highly Stable Alloying Anodes.
The pulverization of alloying anodes significantly restricts their use in lithium-ion batteries (LIBs). This study presents a dual-phase solid electrolyte interphase (SEI) design that incorporates finely dispersed Al nanoparticles within the LiPON matrix. This distinctive dual-phase structure imparts high stiffness and toughness to the integrated SEI film. In comparison to single-phase LiPON film, the optimized Al/LiPON dual-phase SEI film demonstrates a remarkable increase in fracture toughness by 317.8 %, while maintaining stiffness, achieved through the substantial dissipation of strain energy. Application of the dual-phase SEI film on an Al anode leads to a 450 % enhancement in cycling stability for lithium storage in dual-ion batteries. A similar enhancement in cycling stability for silicon anodes, which face severe volume expansion issues, is also observed, demonstrating the broad applicability of the dual-phase SEI design. Specifically, homogeneous Li-Al alloying has been observed in conventional LIBs, even when paired with a high mass loading LiNi0.5 Co0.3 Mn0.2 O2 cathode (7 mg cm-2 ). The dual-phase SEI film design can also accelerate the diffusion kinetics of Li-ions through interface electronic structure regulation. This dual-phase design can integrate stiffness and toughness into a single SEI film, providing a pathway to enhance both the structural stability and rate capability of alloying anodes.


Examining COVID-19 Preventive Behaviors among Cancer Survivors in the United States: An Analysis of the COVID-19 Impact Survey.
The COVID-19 pandemic has impacted adults with chronic diseases, and their health care delivery. Patterns of COVID-19-related preventive behaviors practiced by cancer survivors are unknown, including practices related to canceling doctor's appointments. We evaluated COVID-19-related preventive behaviors among cancer survivors in the United States. We used nationally representative data of 10,760 U.S. adults from the COVID-19 Impact Survey. We defined cancer survivors as those with a self-reported diagnosis of cancer (n = 854, 7.6%). We present frequencies and χ2 tests to evaluate COVID-19-related preventive behaviors among cancer survivors. We estimated determinants of canceling doctor's appointments among cancer survivors using Poisson regression models. Cancer survivors were more likely to practice preventive behaviors, including social distancing (93%, χ2 P < 0.001), wearing a face mask (93%, χ2 P < 0.001), and avoiding crowded areas (84%, χ2 P < 0.001) compared with adults without cancer. Cancer survivors were more likely to cancel doctor's appointments (41%, χ2 P < 0.001), whereas they were less likely to cancel other social activities such as work (19%, χ2 P < 0.001) and school-related (13%, χ2 P < 0.001) activities. After adjustment for covariates, while non-Hispanic (NH)-Black cancer survivors were less likely to cancel a doctor's appointment compared with NH-White cancer survivors, cancer survivors aged 18 to 29, who were female, and who had least one comorbid condition were more likely. Cancer survivors are adhering to recommended preventive behaviors. Cancer survivor's continuity of care may be impacted by COVID-19, specifically young adults, females, and those with existing comorbid conditions. Insights into cancer survivors whose care may be most impacted by COVID-19 will be valuable toward surveillance and survivorship of U.S. cancer survivors.


Correction of inverted nipple: an alternative method using two triangular areolar dermal flaps.
Inverted nipple, which is defined as a nipple located on a plane lower than the areola, presents both functional and cosmetic problems. It is a source of repeated irritation and inflammation, and interferes with nursing. In addition, its abnormal appearance may cause psychological distress. Inverted nipples are congenital or acquired, and are classified as the umbilicated and invaginated types or divided into 3 groups (grades 1, 2, and 3). With consideration of its underlying pathophysiologic components and severity, various surgical procedures have been proposed. For correcting the inverted nipple, the authors introduce an alternative, simple method using 2 triangular areolar dermal flaps. Compared with other methods using triangular areolar dermal flaps, each triangle is approximately 1 mm shorter than the diameter of the nipple, and the deepithelialized areolar dermal flaps are lodged at the slit in the bundle of the lactiferous ducts in the grade 2 inverted nipple. From August 2000 to December 2001, 11 patients (16 nipples) were treated. Five patients had bilateral inverted nipples. Patient age at operation ranged from 18 to 31 years (mean age, 27 years). All nipples were congenital and they had no previous operation. Thirteen nipples were grade 2 and 3 were grade 3 according to the classification of inverted nipple by Han and Hong. The mean follow-up period was 8.7 months (range, 3-12 months). Follow-up examinations revealed no evidence of recurrence of inversion. There was no complication associated with surgery, such as infection, hematoma, permanent sensory disturbance, or nipple necrosis. The resulting scars were minimal. All patients were satisfied with their results. The authors conclude that their procedure is reliable, preserves the lactiferous ducts in grade 2 inverted nipple, requires no special postoperative care, and leaves minimal scars and no recurrence of inversion. This technique can be applied to any type of inverted nipple as a primary surgical procedure.


Cysteine Protease Cathepsins in Atherosclerotic Cardiovascular Diseases.
Atherosclerotic cardiovascular disease (ASCVD) is an inflammatory disease characterized by extensive arterial wall matrix protein degradation. Cysteine protease cathepsins play a pivotal role in extracellular matrix (ECM) remodeling and have been implicated in the development and progression of atherosclerosis-based cardiovascular diseases. An imbalance in expression between cathepsins (such as cathepsins S, K, L, C) and their inhibitor cystatin C may favor proteolysis of ECM in the pathogenesis of cardiovascular disease such as atherosclerosis, aneurysm formation, restenosis, and neovascularization. New insights into cathepsin functions have been made possible by the generation of knockout mice and by the application of specific inhibitors. Inflammatory cytokines regulate the expression and activities of cathepsins in cultured vascular cells and macrophages. In addition, evaluations of the possibility of cathepsins as a diagnostic tool revealed that the circulating levels of cathepsin S, K, and L, and their endogenous inhibitor cystatin C could be promising biomarkers in the diagnosis of coronary artery disease, aneurysm, adiposity, peripheral arterial disease, and coronary artery calcification. In this review, we summarize the available information regarding the mechanistic contributions of cathepsins to ASCVD.


Cell cycle G2/M arrest and activation of cyclin-dependent kinases associated with low-dose paclitaxel-induced sub-G1 apoptosis.
Paclitaxel is a potential anti-cancer agent for several malignancies including ovary, breast, and head and neck cancers. This study investigated the kinetics of paclitaxel-induced cell cycle perturbation in two human nasopharyngeal carcinoma (NPC) cell lines, NPC-TW01 and NPC-TW04. NPC cells treated with higher concentrations (0.1 or 1 micro M) of paclitaxel showed obvious G2/M arrest and then converted to a cell population with reduced DNA content, which was detected as a sub-G2 peak in the flow cytometric histographs. If a low concentration (5 nM) of paclitaxel was used instead, transient G2/M arrest was observed in NPC cells, which subsequently converted to a sub-G1 form during the treatment period. Internucleosomal fragmentation and chromatin condensation were detectable in these sub-G1 and sub-G2 cells, suggesting that persistent or transient G2/M arrest is a prerequisite step for apoptosis elicited by varying doses of paclitaxel. The levels of cyclins A, B1, D1, E, CDK 1 (CDC 2), CDK 2 and proliferating cell nuclear antigen (PCNA) were unchanged in NPC cells following treatment with any concentration of paclitaxel; however, apoptosis-related cyclin B1-associated CDC 2 kinase was highly activated by paclitaxel even at concentrations as low as 5 nM, which is consistent with the finding that low-dose paclitaxel is also able to induce apoptosis in NPC cells. Activation of cyclin B1-associated CDC 2 kinase seems to be an important G2/M event required for paclitaxel-induced apoptosis, and this activation of cyclin B1/CDC 2 kinase could be attributed to the increased activity of CDK 7 kinase.


Effects of citrus and avocado irrigation and nitrogen-form soil amendment on host selection by adult Homalodisca vitripennis (Hemiptera: Cicadellidae).
Host plant water status is thought to influence dispersal of the xylophagous leafhopper Homalodisca vitripennis Germar, especially where plants are grown under high evaporative demand. Preference by adult H. vitripennis for plants grown under different water deficit and nitrogen form fertilization regimens was studied under laboratory conditions. Leafhopper abundance and ovipositional preference were studied on potted 'Washington navel' orange and 'Haas' avocado in cage choice tests, and feeding rate was estimated using excreta produced by insects confined on plants. A similar study compared responses to citrus treated with 1:1 and 26:1 ratios of fertigated nitrate-N to ammonium-N. The insects were more abundant, oviposited, and fed significantly more on surplus-irrigated plants than on plants under moderate continuous deficit irrigation except avocado feeding, which was nearly significant. Plants exposed to drought became less preferred after 3 and 7 d in avocado and citrus, respectively. Citrus xylem fluid tension at this point was estimated at 0.93 MPa. A corresponding pattern of decline in feeding rate was observed on citrus, but on avocado, feeding rate was low overall and not statistically different between treatments. No statistical differences in abundance, oviposition, or feeding were detected on citrus fertigated with 26:1 or 1:1 ratios of nitrate-N to ammonium-N. Feeding occurred diurnally on both plant species. Discussion is provided on the potential deployment of regulated deficit irrigation to manage H. vitripennis movement as part of a multitactic effort to minimize the risk of disease outbreaks from Xylella fastidiosa Wells et al. in southern California agriculture.


Effects of a Curriculum Addressing Racism on Pediatric Residents' Racial Biases and Empathy.
Racism is a longstanding driver of health inequities. Although medical education is a potential solution to address racism in health care, best practices remain unknown. We sought to evaluate the impact of participation in a curriculum addressing racism on pediatric residents' racial biases and empathy. A pre-post survey study was conducted in 2 urban, university-based, midsized pediatric residency programs between July 2019 and June 2020. The curriculum sessions included Self-Reflection on Implicit Bias, Historical Trauma, and Structural Racism. All sessions were paired with empathy and perspective-taking exercises and were conducted in small groups to facilitate reflective discussion. Wilcoxon signed rank tests were used to assess changes in racial bias and empathy. Linear regression was used to assess the effect of resident characteristics on racial bias and empathy. Ninety of 111 residents receiving the curriculum completed pre-surveys (81.1%), and among those, 65 completed post-surveys (72.2%). Among participants with baseline pro-White bias, there was a statistically significant shift (0.46 to 0.36, P=.02) toward no preference. Among participants with a baseline pro-Black bias, there was a statistically significant shift (-0.38 to -0.21, P=.02), toward no preference. Among participants with baseline pro-White explicit bias, there was a statistically significant shift (0.54 to 0.30, P<.001) toward no preference. Among all residents, there was a modest but statistically significant decrease in mean empathy (22.95 to 22.42, P=.03). Participation in a longitudinal discussion-based curriculum addressing racism modestly reduced pediatric residents' racial preferences with minimal effects on empathy scales.