Genome-Wide Identification of GmSPS Gene Family in Soybean and Expression Analysis in Response to Cold Stress.
Sucrose metabolism plays a critical role in development, stress response, and yield formation of plants. Sucrose phosphate synthase (SPS) is the key rate-limiting enzyme in the sucrose synthesis pathway. To date, genome-wide survey and comprehensive analysis of the SPS gene family in soybean (Glycine max) have yet to be performed. In this study, seven genes encoding SPS were identified in soybean genome. The structural characteristics, phylogenetics, tissue expression patterns, and cold stress response of these GmSPSs were investigated. A comparative phylogenetic analysis of SPS proteins in soybean, Medicago truncatula, Medicago sativa, Lotus japonicus, Arabidopsis, and rice revealed four families. GmSPSs were clustered into three families from A to C, and have undergone five segmental duplication events under purifying selection. All GmSPS genes had various expression patterns in different tissues, and family A members GmSPS13/17 were highly expressed in nodules. Remarkably, all GmSPS promoters contain multiple low-temperature-responsive elements such as potential binding sites of inducer of CBF expression 1 (ICE1), the central regulator in cold response. qRT-PCR proved that these GmSPS genes, especially GmSPS8/18, were induced by cold treatment in soybean leaves, and the expression pattern of GmICE1 under cold treatment was similar to that of GmSPS8/18. Further transient expression analysis in Nicotiana benthamiana and electrophoretic mobility shift assay (EMSA) indicated that GmSPS8 and GmSPS18 transcriptions were directly activated by GmICE1. Taken together, our findings may aid in future efforts to clarify the potential roles of GmSPS genes in response to cold stress in soybean.


Thrombolysis with Systemic Recombinant Tissue Plasminogen Activator in Children: A Multicenter Retrospective Study
This study aimed to evaluate systemic thrombolysis experiences with recombinant tissue plasminogen activator (rtPA). Retrospective data were collected from 13 Turkish pediatric hematology centers. The dose and duration of rtPA treatment, concomitant anticoagulant treatment, complete clot resolution (CCR), partial clot resolution (PCR), and bleeding complications were evaluated. Low-dose (LD) rtPA treatment was defined as 0.01-0.06 mg/kg/h and high-dose (HD) rtPA as 0.1-0.5 mg/kg/h. Between 2005 and 2019, 55 thrombotic episodes of 54 pediatric patients with a median age of 5 years (range: 1 day to 17.75 years) were evaluated. These patients had intracardiac thrombosis (n=16), deep vein thrombosis (DVT) (n=15), non-stroke arterial thrombosis (n=14), pulmonary thromboembolism (PE) (n=6), and stroke (n=4). The duration from thrombus detection to rtPA initiation was a median of 12 h (range: 2-504 h) and it was significantly longer in cases of DVT and PE compared to stroke, non-stroke arterial thrombosis, and intracardiac thrombosis (p=0.024). In 63.6% of the episodes, heparin was initiated before rtPA treatment. LD and HD rtPA were administered in 22 and 33 of the episodes, respectively. Concomitant anticoagulation was used in 90% and 36% of the episodes with LD and HD rtPA, respectively (p=0.0001). Median total duration of LD and HD rtPA infusions was 30 h (range: 2-120 h) and 18 h (2-120 h), respectively (p=0.044). Non-fatal major and minor bleeding rates were 12.5% and 16.7% for LD and 3.2% and 25.8% for HD rtPA, respectively. At the end of the rtPA infusions, CCR and PCR were achieved in 32.7% and 49.0% of the episodes, respectively. The most successful site for thrombolysis was intracardiac thrombosis. HD versus LD rtPA administration was not correlated with CCR/PCR or bleeding (p>0.05). Systemic thrombolytic therapy may save lives and organs effectively if it is used at the right indications and the right times in children with high-risk thrombosis by experienced hematologists with close monitoring of recanalization and bleeding.


Effects of hospital volume of primary percutaneous coronary interventions on angiographic results and in-hospital outcomes for acute myocardial infarction.
Several clinical studies have demonstrated an inverse relationship between hospital volume of primary percutaneous coronary interventions (PCI) and in-hospital mortality. However, the relationships among hospital primary PCI volume, angiographic results, and in-hospital prognosis in patients with acute myocardial infarction (AMI) have not been fully investigated in Japan. Using the AMI-Kyoto Multi-Center Risk Study database between January 2000 and December 2005, hospitals were classified into quintiles based on their annual volume of primary PCI. The fifth quintile of hospitals was labeled as high-volume, and the other quintiles were combined and defined as low-volume. Although patients undergoing primary PCI in high-volume hospitals (high-volume group, n=764) had a larger number of diseased vessels at initial coronary angiography and lower Thrombolysis In Myocardial Infarction (TIMI) flow grade in the infarct-related artery before PCI, compared with those in low-volume hospitals (low-volume group, n=1,021), the rates of achieving TIMI flow grade 3 just after PCI in the high-volume group was significantly higher than that in the low-volume group. The overall in-hospital mortality did not differ between the 2 groups. On multivariate analysis, in AMI patients undergoing primary PCI, Killip class >or=3 at admission, multivessel disease or left main trunk (LMT) as culprit lesion, number of diseased vessels >or=2 or diseased LMT, and age were the independent positive predictors of in-hospital mortality, whereas the TIMI flow grade 3 after primary PCI and elapsed time <24 h were the negative ones, but not low-volume hospital. Angiographic results of primary PCI in high-volume hospitals were superior to those in low-volume hospitals, but there was no significant difference in the in-hospital mortality between AMI patients in high-volume hospitals and those in low-volume hospitals.


Action of therapeutic laser and ultrasound in peripheral nerve regeneration.
To assess the efficacy of early therapeutic laser and ultrasound in the regeneration process of an injury in rats. We used 24 rats. Eighteen underwent surgery for sciatic nerve compression by a hemostat above the popliteal fossa. The animals were divided into three groups of six animals each. Normal control group. GI: Injured control without therapeutic intervention. GII: laser ArGaAl therapeutic intervention. GIII: therapeutic intervention of Pulsed Ultrasound. We begin therapeutic interventions 24 hours after injury, with daily applications for a period of fourteen consecutive days. IN ASSESSING THE GIRTH OF THE MUSCLES OF THE RIGHT THEY, THE FOLLOWING AVERAGE DECREASE (IN MM) FOR EACH GI: 0.45, GII: 0.42, GIII: 0.40 In relation to travel time, both GII and GIII presented significant difference when compared to GI. In the final evaluation of the IFC, GII excelled in the GIII. As for the healing observed, a major great improvement was observed in GII and GIII. The results showed that nerve recovery was higher with the laser application. Level of evidence II, Therapeutic Studies - Investigation of the results of treatment.


Highly Sensitive RNA-Based Electrochemical Aptasensor for the Determination of C-Reactive Protein Using Carbon Nanofiber-Chitosan Modified Screen-Printed Electrode.
C-reactive protein (CRP) is one of the biomarkers related to coronavirus disease 2019 (COVID-19). Therefore, it is crucial to develop a highly sensitive, selective, and cost-effective biosensor for the determination of CRP. In this study, we designed an electrochemical aptasensor. For this purpose, the surface of a carbon screen-printed electrode was first modified with a carbon nanofiber-chitosan (CNFs-CHIT) nanocomposite. After that, the amino-terminal RNA aptamer probes were linked to the amino groups of CHIT via glutaraldehyde as the cross-linker. Finally, methylene blue (MB) as a redox probe was self-assembled on the surface of the aptasensor. The obtained results indicated that the CNFs-CHIT nanocomposite increased the surface coverage of the aptamer up to 5.9 times. The square-wave voltammetry was used for the measurement of CRP concentration in the linear range of 1.0-150.0 pM. The obtained results indicated that the signal had a logarithmic relationship with the concentration of CRP. The limit of detection (LOD) was obtained to be 0.37 pM. The dissociation constant (Kd) that demonstrates the affinity of the aptamer probe to its target was found to be 0.93 pM. The analytical performances of the proposed RNA aptasensor were better than the previously reported aptasensors for CRP. The proposed aptasensor was also applied for the determination of CRP in the human plasma samples. The obtained results indicated that there were no statistically significant differences between the responses of the proposed RNA aptasensor and an enzyme-linked immunosorbent assay kit (ELISA). The analytical performances of the proposed RNA aptasensor described in this paper are better than previously reported aptasensors for CRP determination.


Post-acute sequelae of COVID-19 symptom phenotypes and therapeutic strategies: A prospective, observational study.
Post-acute sequelae of COVID-19 (PASC) includes a heterogeneous group of patients with variable symptomatology, who may respond to different therapeutic interventions. Identifying phenotypes of PASC and therapeutic strategies for different subgroups would be a major step forward in management. In a prospective cohort study of patients hospitalized with COVID-19, 12-month symptoms and quantitative outcome metrics were collected. Unsupervised hierarchical cluster analyses were performed to identify patients with: (1) similar symptoms lasting ≥4 weeks after acute SARS-CoV-2 infection, and (2) similar therapeutic interventions. Logistic regression analyses were used to evaluate the association of these symptom and therapy clusters with quantitative 12-month outcome metrics (modified Rankin Scale, Barthel Index, NIH NeuroQoL). Among 242 patients, 122 (50%) reported ≥1 PASC symptom (median 3, IQR 1-5) lasting a median of 12-months (range 1-15) post-COVID diagnosis. Cluster analysis generated three symptom groups: Cluster1 had few symptoms (most commonly headache); Cluster2 had many symptoms including high levels of anxiety and depression; and Cluster3 primarily included shortness of breath, headache and cognitive symptoms. Cluster1 received few therapeutic interventions (OR 2.6, 95% CI 1.1-5.9), Cluster2 received several interventions, including antidepressants, anti-anxiety medications and psychological therapy (OR 15.7, 95% CI 4.1-59.7) and Cluster3 primarily received physical and occupational therapy (OR 3.1, 95%CI 1.3-7.1). The most severely affected patients (Symptom Cluster 2) had higher rates of disability (worse modified Rankin scores), worse NeuroQoL measures of anxiety, depression, fatigue and sleep disorder, and a higher number of stressors (all P<0.05). 100% of those who received a treatment strategy that included psychiatric therapies reported symptom improvement, compared to 97% who received primarily physical/occupational therapy, and 83% who received few interventions (P = 0.042). We identified three clinically relevant PASC symptom-based phenotypes, which received different therapeutic interventions with varying response rates. These data may be helpful in tailoring individual treatment programs.


Technical note: validation of rumination collars for beef cattle.
Two studies were conducted to evaluate a wireless rumination monitoring system (Hi-Tag; SCR Engineers Ltd., Netanya, Israel) for recording rumination in beef cattle. The system operates based on acoustics of rumination and has been used previously for monitoring rumination in both young and adult dairy cattle. Study 1 consisted of beef cattle in tie-stall housing with 72 observations for 4 cattle fed a high forage backgrounding diet and 47 observations for 3 cattle fed a high grain finishing diet. Study 2 consisted of 44 observations for 6 beef cattle fed a high forage diet in a loose-housing feedlot pen. Each observation consisted of the rumination time during a 2-h period as estimated by visual observations made by trained observers (inter-observer correlation r = 0.97) and the Hi-Tag system. The mean difference between visual and Hi-Tag rumination times was 9.8 ± 18.7 min/2 h. The rumination times from the Hi-Tag system were only moderately correlated with visual observations (r = 0.41, P < 0.001). The difference between visual and Hi-Tag rumination times was not correlated with head posture during the 2 h period (r = -0.02, P = 0.89). Physical and dietary differences between dairy and beef cattle may have resulted in the inaccuracy of the Hi-Tag system when used in beef cattle fed typical backgrounding and finishing diets. More work is required to improve the accuracy of this automated system for rumination monitoring before it can be used reliably with beef cattle.


[Paste-like sour milk product for infant nutrition].
A paste-like sour milk manufactured by means of souring the milk base (condensed or recovered skim milk containing 28-30% of dry substances) and various food constituents with the use of a ferment prepared on the basis of pure cultures of acidophilic bacillus maintains its properties of a temperature of 4-6 degrees C for 30 days. The product is manufactured ready for use, and as regards the composition, it approximates breast milk after dilution with water (1 : 3). It may be recommended for infant feeding.


Racial Disparities in Failure to Rescue after Pediatric Heart Surgeries in the US.
To identify the trend in failure to rescue (FTR) and risk factors contributing to racial disparities in FTR after pediatric heart surgery using contemporary nationwide data. We identified 85 267 congenital heart surgeries in patients <18 years of age from 2009 to 2019 using the Kid's Inpatient Database. The primary outcome was FTR. A mixed-effect logistic regression model with hospital random intercept was used to identify independent predictors of FTR. Among 36 753 surgeries with postoperative complications, the FTR was 7.3%. The FTR decreased from 7.4% in 2009 to 6.3% in 2019 (P = .02). FTR was higher among Black than White children for all years. The FTR was higher among girls (7.2%) vs boys (6.6%), children aged <1 (9.6%) vs 12-17 years (2.4%), and those of Black (8.5%) vs White race (5.9%) (all P < .05). Black race was associated with a higher FTR odds (OR, 1.40; 95% CI, 1.20-1.65) after adjusting for demographics, medical complexity, nonelective admission, and hospital surgical volume. Higher hospital volume was associated with a lower odds of FTR for all racial groups, but fewer Black (19.7%) vs White (31%) children underwent surgery at high surgical volume hospitals (P < .001). If Black children were operated on in the same hospitals as White children, the racial differences in FTR would decrease by 47.3%. Racial disparities exist in FTR after pediatric heart surgery in the US. The racial differences in the location of care may account for almost half the disparities in FTR.


Lack of body weight measurement is associated with mortality and hospitalization in community-dwelling frail elderly.
Although it is not uncommon for there to be frail older people living in the community, who do not know their weight and/or height, the health-related outcomes of those older remains unknown. We examined whether missing these anthropometries are a predictor of mortality or hospitalization during a 2-year follow-up period in community-dwelling older people using various community-based services. This study was a prospective cohort analysis of 952 community-dwelling elderly. Data included the clients' demographic characteristics, basic activities of daily living (ADL), comorbidity, and anthropometric measurements at baseline. Analysis of mortality and hospitalization over the 2-year period was conducted using multivariate Cox proportional hazards models. Among the 952 participants, 342 and 292 had missing data for height and weight at baseline, respectively. Multivariate Cox proportional hazards models adjusting for potential confounders showed that the lack of data on weight was associated with 2-year mortality (hazard ratio, HR:1.54, 96% CI:1.09-1.79) as well as hospitalization (HR:1.34, 95% CI:1.01-1.79) during the 2-year follow-up, although the lack of height measurement was not associated with these adverse outcomes. Older people living in the community with unavailable weight data appear to be more likely to have a high risk of mortality and hospitalization.


Tumor necrosis factor, tumor necrosis factor inhibition, and cancer risk.
Tumor necrosis factor (TNF) is a highly pleiotropic cytokine with multiple activities other than its originally discovered role of tumor necrosis in rodents. TNF is now understood to play a contextual role in driving either tumor elimination or promotion. Using both animal and human data, this review examines the role of TNF in cancer development and the effect of TNF and TNF inhibitors (TNFis) on malignancy risk. A literature review was performed using relevant search terms for TNF and malignancy. Although administration of TNF can cause tumor regression in specific rodent tumor models, human expression polymorphisms suggest that TNF can be a tumor-promoting cytokine, whereas blocking the TNF pathway in a variety of tumor models inhibits tumor growth. In addition to direct effects of TNF on tumors, TNF can variously affect immunity and the tumor microenvironment. Whereas TNF can promote immune surveillance designed to eliminate tumors, it can also drive chronic inflammation, autoimmunity, angiogenesis, and other processes that promote tumor initiation, growth, and spread. Key players in TNF signaling that shape this response include NF-κB and JNK, and malignant-inflammatory cell interactions, each of which may have different responses to TNF signaling. Focusing on rheumatoid arthritis (RA) patients, where clinical experience is most extensive, a review of the clinical literature shows no increased risk of overall malignancy or solid tumors such as breast and lung cancers with exposure to TNFis. Lymphoma rates are not increased with use of TNFis. Conflicting data exist regarding the risks of melanoma and nonmelanoma skin cancer. Data regarding the risk of recurrent malignancy are limited. Overall, the available data indicate that elevated TNF is a risk factor for cancer, whereas its inhibition in RA patients is not generally associated with an increased cancer risk. In particular, TNF inhibition is not associated with cancers linked to immune suppression. A better understanding of the tumor microenvironment, molecular events underlying specific tumors, and epidemiologic studies of malignancies within specific disease indications should enable more focused pharmacovigilance studies and a better understanding of the potential risks of TNFis.


Herbivore-plant interactions: mixed-function oxidases and secondary plant substances.
The mixed-function oxidases of a polyphagous insect larva (the southern armyworm, Spodoptera eridania) were found to be induced by a diversity of secondary plant substances. The induction proceeds rapidly and in response to a small quantity of secondary substance. Following induction, the larva is less susceptible to dietary poisoning. It is argued that mixed-function oxidases play a major role in protecting herbivores against chemical stress from secondary plant substances.


Role of resilience training on compromising of infertile couples' applicant for divorce: A cross-sectional study.
Divorce is a social issue, which challenges not only the structure of family but also of a society. Studies have shown that infertility affects the marital boredom. In addition, resilience training and emphasizing on increasing piety (religiousness) can help to decrease this boredom. This study aimed to evaluate the resilience training effects on the compromising of infertile couples' applicant for divorce. In this cross-sectional study, 100 infertile couples who had requested for divorce and referred to the Center for consolidation of the family foundation were enrolled. Participants were randomly divided in two categories (n= 50/each): the case group received some consultation classes on social services as well as resilience training by a consultant in 5 sessions lasting 2 hr. In total, 10 hr of treatment; while the control group just received the consultation and social services. Canner and Davidson questionnaires were utilized as pre- and posttest in both groups. Groups answered the resilience's criterion of Canner and Davidson. The resilience training significantly increased the compromises made by couples in the case group compared to the control (p < 0.01). The results showed that 26% of members of the case group relinquished divorce, while 10% of control group members did the same; this difference was statistically significant (p < 0.01). The resilience training leads to increased psychological well-being elements and compromises in infertile couples.


Comparative genomics of two Shewanella xiamenensis strains isolated from a pilgrim before and during travels to the Hajj.
Shewanella xiamenensis has been reported in water environment and in patients and can act as the originator of oxacillinase in gram-negative bacteria. In order to assess genome plasticity and its functional properties related diarrhea symptoms in pilgrim, comparisons of draft genome sequences of the two isolates were conducted with other closely related genomes. We isolated S. xiamenensis 111B and 111D strains from a pilgrim before travels to the Hajj and during travels with diarrhea symptom, respectively. Whole-genome sequencing showed that draft genome size of 111B strain was 5,008,191 bp, containing 49 kb of a putative plasmid. The genome size of 111D was 4,964,295 bp containing 225 kb of a putative plasmid that shared the backbone sequences with the hospital wastewater strain T17. Comparatively, two Hajj strains are identical at 97.3% identity and 98.7% coverage. They are closely related to river water strain, AS58 by SNPs analysis. Notably, a novel blaOXA-48 allele blaOXA-547 was identified in 111D, sharing 99.5% identity with blaOXA-546 and blaOXA-894. Multiple copies of virulence specific genes, such as capsular polysaccharide biosynthesis, O-antigen and lasB (vibriolysin related gene) have been identified specifically in 111D, but absent in 111B strain. The whole genome sequences of S. xiamenensis strain 111B and 111D, including comparative genomic analysis, highlight here the potential for virulence factors that might be related to the cause of diarrhea in humans and also indicate the possible acquisition of pathogenic bacteria, including antibiotic resistance genes or plasmids during the Hajj.


Ultrastretchable Multilayered Fiber with a Hollow-Monolith Structure for High-Performance Strain Sensor.
As a crucial component of data terminal acquisition devices, flexible strain sensor has shown promising applications in numerous fields, such as healthcare, bodynet, the intelligent traffic system, and the robotic system. For stretchable strain sensor, it remains a huge challenge to realize a fine balance of wide detection range and high sensitivity. Here, an electrically conductive carbon nanotube/thermoplastic polyurethane fiber with a multilayered, hollow, and monolith structure, accompanying high stretchability (up to 476% strain) and low density (about 0.46 g/cm3) is fabricated through a facile coaxial wet-spun assembly strategy. The as-prepared fibers with a designed independent sensitive zone and flexible supporting zone possess an ultralow percolation threshold (0.17 wt %) and a tunable size and structure. This structure endows the fiber with a good integration of adequate flexibility, suitable strength, and high elongation at break for wearable electronics. The fiber, which is then assembled as a strain sensor, realizes the perfect combination of the wide sensing range (>350% strain), high sensitivity (gauge factor (GF) = 166.7 at 350% strain), and excellent working durability (>10 000 cycles). Our sensor could also detect small compressing deformations (0.35% N-1 at 0.025-50 N) by capturing the resistance change of the fiber with superior stability. The highly stretchable, light weight, and multilayered fiber with the designed hollow-monolith structure provides a new route for the preparation of high-performance wearable electronics.


A nationwide study of multimedicine use in people treated with cardiovascular medicines in Australia.
Multimorbidity and multimedicine use are common in people with cardiovascular disease and can lead to harms, such as prescribing errors and drug interactions. We quantified multimedicine use in people treated with cardiovascular medicines in a national sample of Australians. Cross-sectional study. Pharmaceutical dispensing claims for a 10% random sample of Australians. Australian adults dispensed any cardiovascular medicine between June and August 2019. None. We quantified the number and type of cardiovascular and non-cardiovascular medicines dispensed during the study period, and the number of unique prescribers, by age and sex. We identified 493,081 people dispensed any cardiovascular medicine (median age = 67 years, 50.2% women). The population prevalence of cardiovascular medicine dispensing increased from 1.7% (n = 10,503) in people 18-34 years to 80.1% (n = 99,271) in people 75-84 years. Cardiovascular medicine dispensing varied by sex; women 18-34 years were more likely to be dispensed any cardiovascular medicine than men (male:female prevalence ratio [PR] = 0.84, 95% confidence interval [CI] = 0.81-0.87), whereas the prevalence of cardiovascular medicine dispensing was higher in men 35-44 years (PR = 1.27, 95% CI 1.24-1.30) and 45-54 years (PR = 1.24, 95% CI 1.22-1.26) and was similar between sexes in people ≥65 years. Overall, both women and men were dispensed a median of 2.0 (interquartile range [IQR] = 1.0-3.0) cardiovascular medicines. Two-thirds of people ≥65 years (73.5%; n = 208,524) were dispensed ≥2 cardiovascular medicines, with 16.6% (n = 6736) of people ≥85 years dispensed five or more. Women and men were dispensed a median of 2.0 (IQR = 1.0-5.0) and 2.0 (IQR = 0.0-4.0) non-cardiovascular medicines, respectively, to treat comorbid conditions, commonly gastroesophageal reflux disease medicines (32.2% of women and 26.6% of men), antibiotics (28.7% of women and 22.4% of men), and antidepressants (26.3% of women and 15.9% of men). One quarter of both sexes had multiple prescribers for their cardiovascular medicines alone, whereas 54.5% (n = 134,939) of women and 49.9% (n = 122,706) of men had multiple prescribers for all medicines. Multimedicine use is common in people treated with cardiovascular medicines and presents a risk for inappropriate prescribing. Understanding the comorbid conditions commonly treated concurrently with cardiovascular disease can help improve co-prescribing guidelines and develop a person-centered approach to multimorbidity treatment.


From Matterhorn to Mt Everest: empowering rescuers and improving medical care in Nepal.
This article describes a private initiative in which professional Swiss rescuers, based at the foot of the Matterhorn, trained Nepalese colleagues in advanced high altitude helicopter rescue and medical care techniques. What started as a limited program focused on mountain safety has rapidly developed into a comprehensive project to improve rescue and medical care in the Mt Everest area for both foreign travelers and the local Nepalese people.


Smad1 and Smad4 are components of the bone morphogenetic protein-4 (BMP-4)-induced transcription complex of the Xvent-2B promoter.
To study the mechanism of transcriptional activation of the Xenopus homeobox gene Xvent-2B, we have delineated the bone morphogenetic protein-4 (BMP-4)-responsive region between -275/-152 in the proximal promoter. Consistent with the BMP-4 inductive nature of this region, this element exhibits transcriptional activation upon ectopic expression of Smad1 and Smad4. Electrophoretic mobility shift assays with total cellular extracts demonstrated that a DNA fragment encompassing this region was competent in the formation of a BMP-4-induced protein-DNA complex containing Smad1. Two different Smad binding regions were localized, a distal binding region for Smad1 containing two GCAT motifs and proximal AGNC binding sites for Smad4, the latter being conserved in other transforming growth factor-beta-responsive elements. Mutation of the Smad4 binding motif completely abolished transcriptional activation, whereas mutation or deletion of the Smad1 recognition sequence inhibited Smad1/Smad4 responsiveness. These results provide a functional characterization and identification of a vertebrate Smad1/Smad4 DNA response element induced by BMP-4 signaling and offers insight into the transcriptional regulation of a component essential for dorsoventral patterning in Xenopus embryos.


Prospective Comparison of Transient Elastography Using Two Different Devices: Performance of FibroScan and FibroTouch.
Transient elastography (TE) using FibroScan (FS) has been established to non-invasively assess liver fibrosis and steatosis. The aim of this study was to compare the recently introduced FibroTouch (FT) device with the established FS with respect to liver stiffness and CAP. Thirty-nine patients with and without liver disease were included. All patients were measured three times with FS (FibroScan 530 compact, Echosens, France) and FT (FibroTouch-FT100, Wuxi Hisky Med, China). For FS, M and XL probe were used according to the manufacturer's specifications. For steatosis, CAP and the comparable FT equivalent UAP (ultrasound attenuation parameter) was determined. Finally, FT and FS were explored in liver tissue-mimicking phantoms. LS between FS and FT correlated well with r=0.91. Root-mean-square (RMS) of the coefficient of variation for LS was better in FS (11.1% vs 27.4%). Bland-Altman analysis showed a 3.1 kPa mean overestimation of LS by FT. In addition, UAP strongly and linearly depended on the BMI following UAP=3.02 × BMI+186. In phantoms, a similar relation was found with UAP (phantom)= 3.78 × BMI + 146 suggesting that UAP is directly calculated from entered BMI instead of assessing shear-wave attenuation. Consequently, RMS-CV was lower for FT (6.0% vs 9.7%). However, if using different BMI, CV-RMS for FT increased to 12.7%. LS of a patient with manifest liver cirrhosis and ascites was 38.8 kPa using the FS-XL probe but almost normal with FT (7.2 kPa). Although LS by FT shows good correlation with LS-FS, it has larger variation, continuously overestimates LS and completely fails in ascites. Moreover, FT-UAP seems to be a misleading parameter for steatosis assessment because it is at least in part calculated from mandatory entered patient data. In conclusion, novel LS cut-off values need to be defined for LS-FT and usage of UAP is not recommended.


Wound care challenges in children and adults with spina bifida: an open-cohort study.
Skin breakdown is a frequent concern for individuals with spina bifida. We explored wound incidence in patients with spina bifida and how it varies across a person's life span and functional neurologic level. We examined the settings in which skin breakdown most commonly occurred, looking for evidence of chronic, non-healing wounds. We also sought to develop criteria to improve wound monitoring. We identified reported wound episodes in an open-cohort study over a 13-year period, examining the hospital and outpatient clinical records of spina bifida patients at Children's National Medical Center (CNMC). Current age, age at wound presentation, sex, weight, functional neurologic level, wound location, setting in which the wound was acquired, the development of a chronic wound, and presence of a shunt were recorded. Of the 376 patients in our clinical population, 123 (average age: 18.8 years, range: infancy-56 years) developed a total of 375 wounds; the majority of patients who developed one wound went on to develop one or more additional wounds, and 20 patients developed chronic wounds. Our data suggest that age bracket (adolescents), wheelchair use, and bare feet, as well as possibly obesity and reduced executive functioning, are key risk factors for wound development. These findings have led to a focused effort to increase wound education and prevention. In addition we report on our early experience using a wound care specialist to champion this initiative.


Expression of MCAM/MUC18 by human melanoma cells leads to increased tumor growth and metastasis.
The cell surface adhesion molecule MCAM (MUC18) is strongly expressed by advanced primary and metastatic melanomas but is weaker and less frequent in nevus cells. Previous studies have shown that MCAM expression correlates with tumor thickness and metastatic potential of human melanoma cells in nude mice. To provide direct evidence that MCAM plays a role in tumor growth and metastasis of human melanoma, the nonmetastatic MCAM-negative primary cutaneous melanoma SB-2 cells were transfected with MCAM cDNA and analyzed subsequently for changes in their tumorigenic and metastatic potential. Enforced expression of MCAM in SB-2 cells rendered them highly tumorigenic and increased their metastatic potential in nude mice as compared with parental and control transfected cells. The transfected cells displayed increased homotypic adhesion, increased attachment to human endothelial cells, decreased ability to adhere to laminin, and increased invasiveness through Matrigel-coated filters. Anti-MCAM monoclonal antibody reversed these functions in the transfected cells but not in control cells. The above changes in function attributed to the expression of MCAM may underlie the contribution of MCAM/MUC18 to the malignant phenotype.


FoxO3a contributes to the reprogramming process and the differentiation of induced pluripotent stem cells.
Induced pluripotent stem (iPS) cells, which are morphologically and functionally similar with embryonic stem (ES) cells, have been successfully generated from somatic cells through defined reprogramming transcription factors. Forkhead class O3a (FoxO3a) has been recently reported to play an important role in the homeostasis and maintenance of certain types of stem cells; however, the role of FoxO3a in the reprogramming process and differentiation of iPS cells remains unclear. In this study, we investigate the function of FoxO3a during the reprogramming process and characterize the properties of iPS cells from FoxO3a-wild type and -null mouse embryonic fibroblasts (MEFs). Our results show that the FoxO3a-null iPS cells are similar to the wild-type iPS cells in the levels of ES cell markers, alkaline phosphatase activity, and formation of teratoma in vivo. The reprogramming process is delayed in the FoxO3a-null MEFs compared to the wild-type MEFs; whereas the overexpression of FoxO3a partially recovers the impaired reprogramming efficiency in the null group. More importantly, FoxO3a deficiency impairs the neuronal lineage differentiation potential of iPS cells in vitro. These results suggest that FoxO3a affects the reprogramming kinetics and the neuronal lineage differentiation potential of the resulting iPS cells. Therefore, this study demonstrates a novel function of FoxO3a in cell reprogramming, which will help the development of alternative strategies for generating iPS cells.


TaqMan Salmonella enterica Detection Kit. Performance Tested Method 020803.
Peanut butter spiked with Salmonella enterica ser. Typhimurium was prepared by an independent laboratory and sent to Applied Biosystems to determine the sensitivity and specificity of the TaqMan Salmonella enterica Detection Kit for detecting Salmonella in peanut butter. The samples were spiked at three levels: five no-spike (0 CFU/25 g); 20 low-spike (0.2 CFU/25 g); and 20 high-spike (2 CFU/25 g). They were coded to create a blind set of 45 samples. The samples were processed based on an unpaired test design that included enrichment in buffered peptone water for the candidate method and lactose broth for the reference method. In the candidate method, a 1 mL aliquot of enriched sample was extracted using PrepMan Ultra Sample Preparation Reagent; the sample was amplified on the Applied Biosystems 7500 real-time PCR system, and analyzed for detection of Salmonella using RapidFinder Version 1.0 software. All samples processed by the candidate method were confirmed by culture according to the U.S. Food and Drug Administration's Bacteriological Analytical Manual procedures. Sensitivity, specificity, and Chi-square analysis were calculated by combining candidate method results with those of the reference method that were collected by the independent laboratory. The TaqMan Salmonella enterica Detection Kit showed 40% sensitivity, 100% specificity, and a Chi-square value equal to 1.52. Chi-square analysis indicated the candidate method and the reference method were comparable. Although the candidate method sensitivity was only 40% when compared with the reference method (unpaired samples), the sensitivity was > 100% when the candidate method results were compared with those of the confirmation method (same sample enrichment).


Analysis of the mineral composition of the human calcified cartilage zone.
As the connecting tissue between the hyaline articular cartilage and the subchondral bone, calcified cartilage zone (CCZ) plays a great role in the force transmission and materials diffusion. However, the questions that remain to be resolved are its mineral composition and organization. In this study, 40 healthy human knee specimens were harvested; first the CCZ was dissected and observed by Safranin O/fast green staining, then CCZ chemical characteristics were measured by using amino acid assay and X-ray diffraction. The percentage of dry weight of type II collagen as an organic compound of CCZ was 20.16% ± 0.96%, lower than that of the hyaline cartilage layer (61.39% ± 0.38%); the percentage of dry weight of hydroxyapatite as an inorganic compound was 65.09% ± 2.31%, less than that of subchondral bone (85.78% ± 3.42%). Our study provides the accurate data for the reconstruction of the CCZ in vitro and the elucidation of CCZ structure and function.


Standardized clinical pathways may potentially help to reduce the opacity of medical treatment in China - reflections on the murder of a doctor in Wenling, Zhejiang.
A doctor was murdered at Wenling First People's Hospital in Zhejiang, China on October 25, 2013. During the incident, a patient assaulted three doctors, resulting in the death of one of the doctors. This incident has led to a heated discussion about the unhealthy doctor-patient relationship in China. There are complex reasons for the strained doctor-patient relationship in China, but one aspect that helped lead to this situation is the opacity of medical treatment. Research has shown that implementation of clinical pathways reduces the variability of clinical practice and improves outcomes. Standardized clinical pathways can provide a standard for evaluation of the rationality of treatment and also suggest a recommended treatment, potentially reducing the opacity of medical treatment in China. However, the standardized clinical pathways that are currently in use in China still need to be improved. The implementation of clinical pathways needs to be increased, those pathways need to be formulated in detail, a supervisory body needs to be established, and the public needs to be better informed. These aspects should be studied further.


Distinct ASIC currents are expressed in rat putative nociceptors and are modulated by nerve injury.
The H(+)-gated acid-sensing ion channels (ASICs) are expressed in dorsal root ganglion (DRG) neurones. Studies with ASIC knockout mice indicated either a pro-nociceptive or a modulatory role of ASICs in pain sensation. We have investigated in freshly isolated rat DRG neurones whether neurones with different ASIC current properties exist, which may explain distinct cellular roles, and we have investigated ASIC regulation in an experimental model of neuropathic pain. Small-diameter DRG neurones expressed three different ASIC current types which were all preferentially expressed in putative nociceptors. Type 1 currents were mediated by ASIC1a homomultimers and characterized by steep pH dependence of current activation in the pH range 6.8-6.0. Type 3 currents were activated in a similar pH range as type 1, while type 2 currents were activated at pH < 6. When activated by acidification to pH 6.8 or 6.5, the probability of inducing action potentials correlated with the ASIC current density. Nerve injury induced differential regulation of ASIC subunit expression and selective changes in ASIC function in DRG neurones, suggesting a complex reorganization of ASICs during the development of neuropathic pain. In summary, we describe a basis for distinct cellular functions of different ASIC types in small-diameter DRG neurones.


Automated scanning probe lithography with n-alkanethiol self-assembled monolayers on Au(111): application for teaching undergraduate laboratories.
Controllers for scanning probe instruments can be programmed for automated lithography to generate desired surface arrangements of nanopatterns of organic thin films, such as n-alkanethiol self-assembled monolayers (SAMs). In this report, atomic force microscopy (AFM) methods of lithography known as nanoshaving and nanografting are used to write nanopatterns within organic thin films. Commercial instruments provide software to control the length, direction, speed, and applied force of the scanning motion of the tip. For nanoshaving, higher forces are applied to an AFM tip to selectively remove regions of the matrix monolayer, exposing bare areas of the gold substrate. Nanografting is accomplished by force-induced displacement of molecules of a matrix SAM, followed immediately by the surface self-assembly of n-alkanethiol molecules from solution. Advancements in AFM automation enable rapid protocols for nanolithography, which can be accomplished within the tight time restraints of undergraduate laboratories. Example experiments with scanning probe lithography will be described in this report that were accomplished by undergraduate students during laboratory course activities and research internships in the chemistry department of Louisiana State University. Students were introduced to principles of surface analysis and gained "hands-on" experience with nanoscale chemistry.


A comparison of steady and pulsatile flow in symmetrically branched tubes.
The purpose of this study was to compare the characteristics of flow in the region of symmetrical bifurcations having branch-to-trunk area ratios of 0.4, 0.8 and 1.2 during steady and pulsatile flow. Flow was visualized with neutrally bouyant particles. Secondary flow was not observed in the branches during either steady or pulsatile flow when the branch-to-trunk area ratio was 0.4. Secondary velocity patterns were not observed in the branches with branch-to-trunk area ratios of 0.8 and 1.2 during pulsatile flow, although they were observed during steady flow. It may be inaccurate, therefore, to characterize pulsatile flow at an instantaneous Reynolds number on the basis of steady flow at the same Reynolds number.


Does vitamin D administration play a role in outcome of patients with acute ischemic stroke? A randomized controlled trial.
Background: Clinical studies have reported improved neurological outcomes in patients who were taking vitamin D supplements. This study investigates the effect of intramuscular (IM) vitamin D supplementation in patients with acute ischemic stroke (AIS) on neurological outcomes and inflammatory marker levels. Methods: This study included patients diagnosed with AIS (n = 60) from the Neurology Unit of Loghman Hakim Hospital, Tehran, Iran, during the year 2019. Patients with AIS were allocated randomly into two groups who received a single dose of 300000 IU IM vitamin D and a control group that did not receive vitamin D supplementation. Serum vitamin D concentration, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels, as primary outcomes, and the Modified Rankin Scale (MRS), the National Institute of Health Stroke Scale (NIHSS), and the Mini-Mental State Examination (MMSE), as secondary outcomes, were measured at the baseline and the end of the study (6 weeks). Results: Eventually, 59 patients with AIS completed the intervention study. A single dose of 300000 IU increased vitamin D level; moreover, vitamin D supplementation improved MRS and IL-6 levels significantly (P = 0.01, P = 0.02, respectively). There were reverse correlations between serum vitamin D and NIHSS and TNF-α after vitamin D administration. However, no statistically significant effect of vitamin D on the TNF-α or NIHSS and MMSE was seen compared to the control group. Conclusion: Vitamin D probably due to a single dose and short duration of administration, as well as a short follow-up period, had no favorable effects on TNF-α level and NIHSS score.


The plus ends of stable microtubules are the exclusive nucleating structures for microtubules in the axon.
Microtubules (MTs) in the axon have a uniform polarity orientation that is recapitulated during recovery from episodes of MT depolymerization (Heidemann, S. R., M. A. Hamborg, S. J. Thomas, B. Song, S. Lindley, and D. Chu. 1984. J. Cell Biol. 99:1289-1295). This tight regulation of their organization indicates that axonal MTs are spatially regulated by discrete nucleating structures comparable in function to the centrosome. Several authors have proposed that an especially stable class of MTs in the axon may serve as these nucleating structures. In a previous report (Baas, P. W., and M. M. Black. 1990. J. Cell Biol. 111:495-509), we determined that the axons of cultured sympathetic neurons contain two classes of MT polymer, stable and labile, that differ in their sensitivity to nocodazole by roughly 35-fold. The stable and labile polymer represent long-lived and recently assembled polymer, respectively. We also determined that these two classes of polymer can be visually distinguished at the immunoelectron microscopic level based on their content of tyrosinated alpha-tubulin: the labile polymer stains densely, while the stable polymer does not stain. In the present study, we have taken advantage of these observations to directly identify MT nucleating structures in the axon. Neuron cultures were treated with nocodazole for 6 h to completely depolymerize the labile polymer in the axon, and substantially shorten the stable polymer. The cultures were then rinsed free of the drug, permitted to reassemble polymer for various periods of time, and prepared for immunoelectron microscopic localization of tyrosinated alpha-tubulin. Serial reconstruction of consecutive thin sections was undertaken to determine the spatial relationship between the stable MTs and the newly assembled polymer. All of the new polymer assembled in direct continuity with the plus ends of stable MTs, indicating that these ends are assembly competent, and hence capable of acting as nucleating structures. Our results further indicate that no self-assembly of MTs occurs in the axon, nor do any MT nucleating structures exist in the axon other than the plus ends of stable MTs. Thus the plus ends of stable MTs are the exclusive nucleating structures for MTs in the axon.


The MicroRNA3686 Inhibits the Proliferation of Pancreas Carcinoma Cell Line by Targeting the Polo-Like Kinase 1.
The Polo-like kinase 1 (PLK1) is one member of the so-called Polo-like kinase family which plays an important role in tumorigenesis. By analyzing the potential complementary microRNA (miRNA) targeting sequence of PLK1, we identified that miRNA-3686 (hereby and thereafter mir3696) could be the potential regulator for PLK1. Real-time PCR demonstrated that the mir3686 has a relatively higher expression in the immortalized pancreas cell HPDE6C7 than pancreas carcinoma derived cell line PANC1. The upregulation of mir3686 in HPDE6C7 cell corresponded with the low expression of PLK1 as well. Both luciferase based reporter assay and evaluation of endogenous PLK1 expression demonstrated that mir3686 regulated PLK1, which confirms our speculation. Moreover, we found that transfection of mir3686 in PANC1 cell could lead to proliferation inhibition and promote apoptosis. Further analysis demonstrated that mir3686 transfection in PANC1 cell also inhibited cell invasion, and clone formation in cell invasion assay and clonogenic cell survival assay, respectively. In contrast, inhibition of mir3686 expression in HPDE6C7 cell enhanced the capability of proliferation, cell invasion and clone formation. Taken together, our results indicated that mir3686 could target PLK1 to inhibit the cell proliferation in pancreas cancer derived cell line and mir3686 could be a new therapeutic target for pancreas cancer treatment.


Synthesis and anticonvulsant activity of phenoxyacetyl derivatives of amines, including aminoalkanols and amino acids.
A series of 17 new phenoxyacetamides has been prepared via multistep chemical synthesis as a continuation of the research carried out by our group on di- and tri-substituted phenoxyalkyl and phenoxyacetyl derivatives of amines. The obtained compounds vary in an amide component, for example aminoalkanol or (un)modified amino acid moieties were introduced. The structures of selected products were confirmed by means of crystallographic methods. All 17 compounds were the subject of preliminary screening for potential anticonvulsant activity (MES, 6 Hz and/or scMET tests) and neurotoxicity (rotarod) in mice after intraperitoneal administration, while several active compounds were subsequently examined in additional models (e.g. MES and rotarod - rats, p.o. or i.p., hippocampal kindling - rats, i.p.). Finally, safety studies (cytotoxicity and cell proliferation assays on astrocytes, metabolic stability assessment, mutagenicity evaluation) were performed for several active compounds, including the most promising one (R-(-)-2-(2,6-dimethylphenoxy)-N-(1-hydroxypropan-2-yl)acetamide, MES ED50 = 12.00 mg per kg b.w., rats, p.o.).


Antioxidant, α-amylase and α-glucosidase activity of various solvent fractions of I. obliquus and the preventive role of active fraction against H2 O2 induced damage in hepatic L02 cells as fungisome.
Inonotus obliquus is a traditional mushroom well known for its therapeutic value. In this study, various solvent fractions of I. obliquus were preliminarily screened for their antioxidant, α-amylase and α-glucosidase inhibition properties. To improve the drug delivery, the active fraction (ethyl acetate fraction) of I. obliquus was synthesized into fungisome (ethyl acetate phophotidyl choline complex, EAPC) and its physical parameters were assessed using Fourier transform infrared spectroscopy (FTIR), High performance liquid chromatography (HPLC), Scanning electron microscope (SEM), and ς potential analysis. Then normal human hepatic L02 cells was used to evaluate the cytotoxicity of EAPC. The results showed that EA fraction possesses significant free radical scavenging, α-amylase and α-glucosidase inhibition properties. FTIR, SEM, and HPLC analysis confirmed the fungisome formation. The particle size of EAPC was 102.80 ± 0.42 nm and the ς potential was -54.30 ± 0.61 mV. The percentage of drug entrapment efficiency was 97.13% and the drug release rates of EAPC in simulated gastric fluid and simulated intestinal fluid were 75.04 ± 0.29% and 93.03 ± 0.36%, respectively. EAPC was nontoxic to L02 cells, however it could selectively fight against the H2 O2 induced oxidative damage in L02 cells. This is the first study to provide scientific information to utilize the active fraction of I. obliquus as fungisome. PRACTICAL APPLICATIONS: Inonotus obliquus (IO) is a traditional medicinal fungus. The extracts of IO have obvious antioxidant and hypoglycemic activities. Ethyl acetate (EA) fraction of IO was encapsulated in liposomes to form EAPC. EAPC has a sustained-release effect. It has nontoxic to L02 cells and could protect L02 cells from oxidative damage caused by hydrogen peroxide. This study could provide new ideas for the treatment of diabetes.


Neutrophils as potential therapeutic targets in hepatocellular carcinoma.
The success of atezolizumab plus bevacizumab treatment contributed to a shift in systemic therapies for hepatocellular carcinoma (HCC) towards combinations that include cancer immunotherapeutic agents. Thus far, the principal focus of cancer immunotherapy has been on interrupting immune checkpoints that suppress antitumour lymphocytes. As well as lymphocytes, the HCC environment includes numerous other immune cell types, among which neutrophils are emerging as an important contributor to the pathogenesis of HCC. A growing body of evidence supports neutrophils as key mediators of the immunosuppressive environment in which some cancers develop, as well as drivers of tumour progression. If neutrophils have a similar role in HCC, approaches that target or manipulate neutrophils might have therapeutic benefits, potentially including sensitization of tumours to conventional immunotherapy. Several neutrophil-directed therapies for patients with HCC (and other cancers) are now entering clinical trials. This Review outlines the evidence in support of neutrophils as drivers of HCC and details their mechanistic roles in development, progression and metastasis, highlighting the reasons that neutrophils are well worth investigating despite the challenges associated with studying them. Neutrophil-modulating anticancer therapies entering clinical trials are also summarized.


Development and validation of a stability-indicative agar diffusion assay to determine the potency of linezolid in tablets in the presence of photodegradation products.
Linezolid (LNZ) is one of the first commercially available (and most widely used) oxazolidinone antibiotics. This study describes the development and validation of a microbiological assay, applying the cylinder-plate method, for the determination of the antibiotic linezolid, as well as the evaluation of the ability of the method in determining the stability of linezolid in tablets. The validation method yielded good results and included linearity, precision, accuracy, robustness and selectivity. The assay is based on the inhibitory effect of LNZ upon the strain of Bacillus subtilis ATCC 9372 used as the test microorganism. The results of the assay were treated statistically by analysis of variance (ANOVA) and were found to be linear (r(2)=0.9998) in the range of 20-80 microg mL(-1), precise (inter-assay: R.S.D.=0.61) and accurate (R.S.D.=1.7). The method developed and validated proved to be indicative of stability and capable of determining the decay of linezolid in the presence of photodegradation products. Comparison of bioassay and liquid chromatography by ANOVA showed no significant difference between methodologies. The results demonstrated the validity of the proposed bioassay, which is a simple and useful alternative methodology for LNZ determination in routine quality control.


Anatomical variations of donor portal vein in right lobe living donor liver transplantation: the safe use of variant portal veins.
In right lobe (RL) living donor liver transplantation (LDLT), portal vein (PV) variations are of immense clinical significance. In this study, we describe in detail our PV reconstruction techniques in RL grafts with variant PV anatomy and evaluate the impact of accompanying biliary variations on the recipient outcomes. In a total of 386 RL LDLTs performed between July 2004 and July 2012, the clinical data on 52 (13%) transplants using RL grafts with variant PV anatomy were retrospectively analyzed. Portal vein anatomy was classified as type 2 in 20 patients, type 3 in 24 patients, and type 4 in eight patients. The PV reconstruction techniques utilized included back-wall plasty (n = 21), back-wall plasty with saphenous vein graft interposition (n = 6), saphenous vein graft interposition (n = 5), cryopreserved iliac vein Y-graft interposition (n = 6), and quiltplasty (n = 3). There was no donor mortality. In a median follow-up of 29 months, none of the recipients had vascular complications. Anomalous PV anatomy was associated with a high (54%) incidence of biliary variations; however, these variations did not result in increased biliary complication rate. Overall, the 1- and 3-year patient survival rates of recipients were 91% and 81%, respectively. Vascular and biliary variations in RL grafts render LDLT technically more challenging. By employing appropriate reconstruction techniques, it is possible to successfully use RL grafts with PV variations without endangering recipient and donor safety.


Affective motives for smoking among early stage smokers.
As most smokers initiate smoking during adolescence, assessment of smoking motives that underlie trajectories of dependence is critical for both prevention and cessation efforts. In the current study, we expected participants with higher nicotine dependence would smoke (a) less for positive reinforcement (PR) and (b) more for negative reinforcement (NR) motives. We secondarily assessed the relative contribution of PR to NR motives across levels of dependence. Data were drawn from a study on cue-elicited craving among occasional versus daily adolescent smokers aged 16-20 years (N = 111). Smoking motives were assessed in relation to 3 commonly used measures of nicotine dependence: (a) Fagerström Test for Nicotine Dependence (FTND), (b) Autonomy over Smoking Scale (AUTOS), and (c) Nicotine Dependence Syndrome Scale (NDSS). Compared to occasional smokers, daily smokers had significantly higher scores on each dependence measure and endorsed more prominent NR smoking motives. Each measure of nicotine dependence was strongly associated with NR motives for smoking, although measures differed in their association with PR motives. As expected, the FTND, AUTOS, and NDSS each significantly predicted smoking motive difference score (PR - NR), such that higher dependence was associated with more prominent NR motives for smoking. Results are consistent with our understanding of dependence and provide further support for 3 common measures of nicotine dependence among early stage smokers.


Discrete and essential roles of the multiple domains of Arabidopsis FHY3 in mediating phytochrome A signal transduction.
Phytochrome A is the primary photoreceptor for mediating various far-red light-induced responses in higher plants. We recently showed that Arabidopsis (Arabidopsis thaliana) FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and FAR-RED-IMPAIRED RESPONSE1 (FAR1), a pair of homologous proteins sharing significant sequence homology to Mutator-like transposases, act as novel transcription factors essential for activating the expression of FHY1 and FHL (for FHY1-like), whose products are required for light-induced phytochrome A nuclear accumulation and subsequent light responses. FHY3, FAR1, and Mutator-like transposases also share a similar domain structure, including an N-terminal C2H2 zinc finger domain, a central putative core transposase domain, and a C-terminal SWIM motif (named after SWI2/SNF and MuDR transposases). In this study, we performed a promoter-swapping analysis of FHY3 and FAR1. Our results suggest that the partially overlapping functions of FHY3 and FAR1 entail divergence of their promoter activities and protein subfunctionalization. To gain a better understanding of the molecular mode of FHY3 function, we performed a structure-function analysis, using site-directed mutagenesis and transgenic approaches. We show that the conserved N-terminal C2H2 zinc finger domain is essential for direct DNA binding and biological function of FHY3 in mediating light signaling, whereas the central core transposase domain and C-terminal SWIM domain are essential for the transcriptional regulatory activity of FHY3 and its homodimerization or heterodimerization with FAR1. Furthermore, the ability to form homodimers or heterodimers largely correlates with the transcriptional regulatory activity of FHY3 in plant cells. Together, our results reveal discrete roles of the multiple domains of FHY3 and provide functional support for the proposition that FHY3 and FAR1 represent transcription factors derived from a Mutator-like transposase(s).


Retinoic acid activates interferon regulatory factor-1 gene expression in myeloid cells.
All-trans-retinoic acid (ATRA) is the drug of choice in the treatment of acute promyelocytic leukemia (APL). ATRA induces both in vitro and in vivo differentiation of APL cells into mature granulocytes. However, the molecular mechanisms involved in ATRA-dependent growth inhibition and cellular differentiation are not presently understood. The NB4 cell line, which is derived from the bone marrow of a patient with APL during relapse, can be used as a model system to study the growth and differentiation of APL cells. Because interferon (IFN) regulatory factors (IRF-1 and IRF-2) and other IFN-inducible gene products regulate cell growth, we analyzed the effects of ATRA on the expression of these genes. We show that ATRA directly activates IRF-1 gene expression, followed by activation of IRF-2 and 2'-5' oligoadenylate synthetase (OAS) gene expression with slower kinetics. In addition to NB4 cells, ATRA also activated IRF-1 gene expression in HL-60, U937, and THP-1 cells, which all respond to ATRA by growth inhibition. A more than additive increase in IRF-1 gene expression was seen with ATRA and IFN-gamma in NB4 cells. ATRA did not activate nuclear factor kappa B or signal transducer and activator of transcription (STAT) activation pathways, suggesting that an alternate mechanism is involved in IRF-1 gene activation. The ATRA-induced expression of IRF-1, an activator of transcription and repressor of transformation, may be one of the molecular mechanisms of ATRA-induced growth inhibition, and the basis for the synergistic actions of ATRA and IFNs in myeloid leukemia cells.


Chemical sulfide oxidation of wastewater--effects of pH and temperature.
In this study, the kinetics and stoichiometry of chemical sulfide oxidation of wastewater from sewer networks were investigated. Based on experiments, it was shown that the stoichiometry could be considered identical for wastewater from two sampling sites. However, the kinetics differed significantly among the wastewaters from the two sites. Effects of pH and temperature were investigated in the pH and temperature ranges 5-9 and 5-25 degrees C, respectively. The rate of chemical sulfide oxidation could be related to the dissociation of H2S to HS-, with HS- being oxidized at a higher rate than H2S. The temperature dependency of the chemical sulfide oxidation rate was described using an Arrhenius relationship. The oxidation rate was found to double with a temperature increase of 12 degrees C. The stoichiometry of the chemical oxidation was not significantly affected by varying pH and temperature. Based on the experiments, a general rate equation, including a stoichiometric coefficient describing chemical sulfide oxidation in wastewater was proposed, enabling the process to be incorporated into sewer process models that can predict odor and corrosion problems.


Evaluation of AUC(0-4) predictive methods for cyclosporine in kidney transplant patients.
Cyclosporine (CyA) is the most commonly used immunosuppressive agent in patients who undergo kidney transplantation. Dosage adjustment of CyA is usually based on trough levels. Recently, trough levels have been replacing the area under the concentration-time curve during the first 4 h after CyA administration (AUC(0-4)). The aim of this study was to compare the predictive values obtained using three different methods of AUC(0-4) monitoring. AUC(0-4) was calculated from 0 to 4 h in early and stable renal transplant patients using the trapezoidal rule. The predicted AUC(0-4) was calculated using three different methods: the multiple regression equation reported by Uchida et al.; Bayesian estimation for modified population pharmacokinetic parameters reported by Yoshida et al.; and modified population pharmacokinetic parameters reported by Cremers et al. The predicted AUC(0-4) was assessed on the basis of predictive bias, precision, and correlation coefficient. The predicted AUC(0-4) values obtained using three methods through measurement of three blood samples showed small differences in predictive bias, precision, and correlation coefficient. In the prediction of AUC(0-4) measurement of one blood sample from stable renal transplant patients, the performance of the regression equation reported by Uchida depended on sampling time. On the other hand, the performance of Bayesian estimation with modified pharmacokinetic parameters reported by Yoshida through measurement of one blood sample, which is not dependent on sampling time, showed a small difference in the correlation coefficient. The prediction of AUC(0-4) using a regression equation required accurate sampling time. In this study, the prediction of AUC(0-4) using Bayesian estimation did not require accurate sampling time in the AUC(0-4) monitoring of CyA. Thus Bayesian estimation is assumed to be clinically useful in the dosage adjustment of CyA.


Simple method for 60-degree Z-plasty.
The 60-degree two-flap Z-plasty is extremely useful and versatile. Its success depends upon accurate construction of the flaps. In the past, the intraoperative measurements required have been either quite involved or quite inaccurate. We present a simple but accurate method for planning the 60-degree two-flap Z-plasty.


Disentangling the roles of point-of-sale ban, tobacco retailer density and proximity on cessation and relapse among a cohort of smokers: findings from ITC Canada Survey.
To examine how point-of-sale (POS) display bans, tobacco retailer density and tobacco retailer proximity were associated with smoking cessation and relapse in a cohort of smokers in Canada, where provincial POS bans were implemented differentially over time from 2004 to 2010. Data from the 2005 to 2011 administrations of the International Tobacco Control (ITC) Canada Survey, a nationally representative cohort of adult smokers, were linked via residential geocoding with tobacco retailer data to derive for each smoker a measure of retailer density and proximity. An indicator variable identified whether the smoker's province banned POS displays at the time of the interview. Outcomes included cessation for at least 1 month at follow-up among smokers from the previous wave and relapse at follow-up among smokers who had quit at the previous wave. Logistic generalised estimating equation models were used to determine the relationship between living in a province with a POS display ban, tobacco retailer density and tobacco retailer proximity with cessation (n=4388) and relapse (n=866). Provincial POS display bans were not associated with cessation. In adjusted models, POS display bans were associated with lower odds of relapse which strengthened after adjusting for retailer density and proximity, although results were not statistically significant (OR 0.66, 95% CI 0.41 to 1.07, p=0.089). Neither tobacco retailer density nor proximity was associated with cessation or relapse. Banning POS retail displays shows promise as an additional tool to prevent relapse, although these results need to be confirmed in larger longitudinal studies.


Yersiniosis in the Bristol Zoo (1955-1974).
Ninety one cases of Yersiniosis occurred betwen 1955 and 1974 at Bristol Zoo. Species affected included a range of primates and birds, a rodent (Capybara) and a carnivore (Caracal Lynx). The incidence of the disease was highest in the winter months. There were variations in the annual incidence of Yersiniosis, with peaks occurring at intervals of 4-6 years. Common pathological findings included miliary focal necrosis and abscess formation.


Prevalence of Barriers and Facilitators to Enhancing Conservative Kidney Management for Older Adults in the Primary Care Setting.
Conservative management of adults with stage 5 CKD (eGFR<15 ml/min per 1.73 m2) is increasingly being provided in the primary care setting. We aimed to examine perceived barriers and facilitators for conservative management of older adults by primary care physicians. In 2015, we conducted a cross-sectional, population-based survey of all primary care physicians in Alberta, Canada. Eligible participants had experience caring for adults ages ≥75 years old with stage 5 CKD not planning on initiating dialysis. Questionnaire items were on the basis of a qualitative descriptive study informed by the Behavior Change Wheel and tested for face and content validity. Physicians were contacted via postal mail and/or fax on the basis of a modified Dillman method. Four hundred nine eligible primary care physicians completed the questionnaire (9.6% response rate). The majority of respondents were men (61.6%), were ages 40-60 years old (62.6%), and practiced in a large/medium population center (68.0%). The most common barrier to providing conservative care in the primary care setting was the inability to access support to maintain patients in the home setting (39.1% of respondents; 95% confidence interval, 34.6% to 43.6%). The second most common barrier was working with nonphysician providers with limited kidney-specific clinical expertise (32.3%; 95% confidence interval, 28.0% to 36.7%). Primary care physicians indicated that the two most common strategies that would enhance their ability to provide conservative management would be the ability to use the telephone to contact a nephrologist or clinical staff from the conservative care clinic (86.9%; 95% confidence interval, 83.7% to 90.0% and 85.6%; 95% confidence interval, 82.4% to 88.9%, respectively). We identified important areas to inform clinical programs to reduce barriers and enhance facilitators to improve primary care physicians' provision of conservative kidney care. In particular, primary care physicians require additional resources for maintaining patients in their home and telephone access to nephrologists and conservative care specialists.


Construction and application of a new watermelon germplasm with the phenotype of dwarf and branchless.
Watermelon (Citrullus lanatus) is a widely cultivated cucurbitaceae crop appreciated by consumers worldwide. However, the long vine and abundant lateral branches of currently cultivated watermelon varieties hinder light simplification and mechanized cultivation, affecting plant spacing and row spacing requirements. To address this, the development of watermelon with dwarf and branchless traits has become a crucial direction for the industry. In previous studies, the genes controlling dwarf (Cldw-1) and branchless (Clbl) traits were mapped and cloned. Marker-assisted selection markers, dCAPS3 and dCAPS10, were developed for these traits, respectively. In this study, the dwarf germplasm WM102 and the branchless germplasm WCZ were crossed to obtain F1 .Further self-crossing of the F1 individuals resulted in the F2 population. Through multiple generations of self-pollination, a new watermelon germplasm DM with double mutation (dwarf and branchless) was obtained. DM exhibited stable inheritance without segregation. Moreover, DM was used as a donor parent for crossing with commercial watermelon materials, and near-isogenic lines (NILs) with the dwarf and branchless traits were developed. These NILs carry additional desirable agronomic traits and provide valuable genetic resources for future watermelon breeding programs, particularly in improving plant architecture and overall quality. The development and application of DM and NILs hold great potential for advancing the watermelon industry toward industrialization, large-scale cultivation, and enhanced plant architecture.


CHINs: making the important decisions.
Community health information networks (CHINs) are an evolving concept. In their most basic form, CHINs provide a structure for sharing financial and clinical information among a defined group of entities. However, several key decisions affect how a CHIN will function. Among those decisions are what "community" will be included, what technical infrastructure to use, what organization or group of organizations will lead the CHIN development effort, what types of information will be shared, and how to safe-guard confidentiality.


The Comparative Macro-Level Ageism Index: An International Comparison.
Ageism, socially constructed discrimination against seniors, influences the quality of life of older adults. This study aimed to compare ageism in 15 Organization for Economic Cooperation and Development (OECD) countries using the scientifically developed Comparative Macro-Level Ageism Index (CMAI). We developed the CMAI by reviewing previous index research on the life of older people and conducting expert interviews using a Delphi method. We identified five domains, economic status, health, employment, environment, and social participation, and 17 indicators of ageism. Standardized ageism scores were compared across 15 OECD countries. The results indicated that the overall ageism score was highest in Turkey and lowest in Japan. Turkey was the most likely while South Korea was the least likely to practice age discrimination in the workplace. Yet, South Korea had the highest score for discriminating against seniors based on economic status while Spain had the lowest score in this domain. Japan had favorable conditions for economic status, health status, and social participation for older adults. Implications of this study and suggestions for further studies on developing an objective indicator of structural age discrimination are discussed.


Desensitization of platelet alpha 2-adrenoceptors after short term infusions of adrenoceptor agonist in man.
The effect of intravenous infusion of catecholamines and related drugs on human platelet alpha 2-adrenoceptor number and function was investigated. Short (60-120 min) infusions of catecholamines with alpha 2 agonist activity in vivo produced attenuation of the platelet responses to adrenaline in vitro. This desensitization was specific for the adrenaline induced aggregatory response. The maximum number of [3H]yohimbine binding sites on platelets was not altered by adrenaline infusion. The ability of adrenaline to reduce platelet cyclic AMP levels was significantly reduced after the infusions. Acute infusions of alpha 2-adrenoceptor agonists may alter the coupling of the platelet alpha 2-adrenoceptor to adenylate cyclase.


Vitamin D dependent effects of APOA5 polymorphisms on HDL cholesterol.
Vitamin D and serum lipid levels are risk factors for cardiovascular disease. We sought to determine if vitamin D (25OHD) interacts at established lipid loci potentially explaining additional variance in lipids. 1060 individuals from Utah families were used to screen 14 loci for SNPs potentially interacting with dietary 25OHD on lipid levels. Identified putative interactions were evaluated for (1) greater effect size in subsamples with winter measures, (2) replication in an independent sample, and (3) lack of gene-environment interaction for other correlated dietary factors. Maximum likelihood models were used to evaluate interactions. The replicate sample consisted of 2890 individuals from the Family Heart Study. Putative 25OHD receptor binding site modifying SNPs were identified and allele-specific, 25OHD-dependent APOA5 promoter activity examined using luciferase expression assays. An additional sample with serum 25OHD measures was analyzed. An rs3135506-25OHD interaction influencing HDL-C was identified. The rs3135506 minor allele was more strongly associated with low HDL-C in individuals with low winter dietary 25OHD in initial and replicate samples (p=0.0003 Utah, p=0.002 Family Heart); correlated dietary factors did not explain the interaction. SNP rs10750097 was identified as a putative causative polymorphism, was associated with 25OHD-dependent changes in APOA5 promoter activity in HEP3B and HEK293 cells (p<0.01), and showed similar interactions to rs3135506 in family cohorts. Linear interactions were not significant in samples with serum 25OHD measures; however, genotype-specific differences were seen at deficient 25OHD levels. A 25OHD receptor binding site modifying APOA5 promoter polymorphism is associated with lower HDL-C in 25OHD deficient individuals.


Light and electron microscopical observations on the Leydig cells of the scrotal and abdominal testes of naturally unilateral cryptorchid West African dwarf goats.
The structure of interstitial cells of Leydig in the scrotal and abdominal testes of adult West African dwarf goats was studied utilising light and electron microscopy. The Leydig cells in both testes were scattered singly, in cords or clusters in the intertubular connective tissue in close proximity to vascular elements. The intertubular connective tissue in the abdominal testes was however much wider because of the hypoplasia of the seminiferous tubules. While the cells of the scrotal testes exhibited non-granular, pale staining cytoplasm, those of the abdominal testes were darkly staining and the majority contained coarse intracytoplasmic osmiophilic granules Interspersed amongst these cells were adipose cells occasionally distributed overall. With the electron microscope, it was found that agranular endoplasmic reticulum, Golgi apparatus and mitochondria were more prominently developed in the scrotal testes. In marked contrast, there were numerous lipid droplets in the cytoplasm of the Leydig cells in the abdominal testes. Furthermore, the cytoplasm of several of these cells showed evidence of degeneration. It is concluded that, contrary to observations in the experimentally induced condition, abdominal retention of testes in natural unilateral cryptorchidism induces alterations in the light microscopical and ultrastructural features of the Leydig cells of West African dwarf goats, changes which possibly can be ascribed to the chronic decline in testicular blood flow and the elevated temperature of the abdominal environment.


Non-g Factors Predict Educational and Occupational Criteria: More than g.
In a prior issue of the Journal of Intelligence, I argued that the most important scientific issue in intelligence research was to identify specific abilities with validity beyond g (i.e., variance common to mental tests) (Coyle, T.R. Predictive validity of non-g residuals of tests: More than g. Journal of Intelligence 2014, 2, 21-25.). In this Special Issue, I review my research on specific abilities related to non-g factors. The non-g factors include specific math and verbal abilities based on standardized tests (SAT, ACT, PSAT, Armed Services Vocational Aptitude Battery). I focus on two non-g factors: (a) non-g residuals, obtained after removing g from tests, and (b) ability tilt, defined as within-subject differences between math and verbal scores, yielding math tilt (math > verbal) and verbal tilt (verbal > math). In general, math residuals and tilt positively predict STEM criteria (college majors, jobs, GPAs) and negatively predict humanities criteria, whereas verbal residuals and tilt show the opposite pattern. The paper concludes with suggestions for future research, with a focus on theories of non-g factors (e.g., investment theories, Spearman's Law of Diminishing Returns, Cognitive Differentiation-Integration Effort Model) and a magnification model of non-g factors.


Normal human oral keratinocytes are more sensitive to N-methyl-N'-nitro-N-nitrosoguanidine-induced cytotoxicity and apoptosis than HPV-immortalized oral keratinocytes.
Exposure of HPV-immortalized, but not normal human oral keratinocytes, to the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) renders the cells tumorigenic. The underlying mechanism of this differential response of normal and immortalized cells was investigated. Normal primary human oral keratinocytes and three HPV-immortalized human oral keratinocyte cell lines exposed to MNNG were evaluated for survival rate, single and double-strand DNA breaks, and the expression of p53 and bcl-2 proteins. MNNG exposure for 2 h induced both greater cytotoxicity and a more rapid kinetic of cell death in normal keratinocytes than in the immortalized cells. Further, normal keratinocytes were more sensitive to lower concentrations of MNNG that were subtoxic for the immortalized cells. Likewise, with lower concentration of MNNG (50 mu M), significant single-strand DNA breaks in normal keratinocytes were induced whereas no such effect was seen in the immortalized cells. Double-strand DNA fragmentation (apoptosis) was observed in normal keratinocytes exposed to 50 mu M MNNG but not in the immortalized cells. Higher concentrations of MNNG (100 mu M) were toxic to both normal and immortalized cells although the normal cells were still more sensitive and with faster kinetics of cell death. MNNG-induced apoptosis was not attributable to down regulation of the anti-apoptotic product bcl-2 in normal cells; however, exposure of normal keratinocytes to MNNG did result in induction of the apoptotic gene p53. No change in p53 level was seen in the immortalized cells. These findings suggest that the selective sensitivity of normal keratinocytes to MNNG-induced apoptosis is in part due to the induction of p53. The HPV-immortalized cells are resistant to MNNG-induced apoptosis and therefore are capable of undergoing mutations affecting cell proliferation and resulting in tumori-genicity.


Newborn screening for sickle cell disease in Jamaica: a review - past, present and future.
Newborn screening (NBS) for sickle cell disease (SCD) has occurred in Jamaica since 1973 in two periods, the most recent being since 1995. As a result of NBS, significant lessons have been learnt about management of the disease. Additionally, significant improvements in morbidity and mortality of children affected with the disease have occurred because of the implementation of simple interventions. Unfortunately, in a country where the burden of disease is high compared to other countries, only approximately 40% of children born in Jamaica currently benefit from NBS. As such, the future of NBS for SCD in Jamaica lies in island-wide screening. There are challenges including the lack of appropriate governance and policy structures, the technology for high-volume processing and comprehensive care clinics throughout the island. On the other hand, the significant strides made in disease management, the strength and model of care of the Sickle Cell Unit, delicately balancing limited resources and increased survival cannot be disparaged. Therefore, consistent with the World Health Organization's recommendation, we are working toward achieving island-wide screening for SCD, to ensure equitable access to continued improvements in morbidity, mortality and quality of life.


Palliative care for patients with motor neurone disease and their bereaved carers: a qualitative study.
Internationally, it is widely accepted that holistic care is as an integral part of the care for people with motor neurone disease (MND), and their informal carers. However the optimal role of generalist and specialist palliative care, and how it integrates with specialist neurology services, is not fully established. Using a qualitative approach we sought to examine end of life care for people with MND in Northern Ireland, and the role of specialist and generalist palliative care. Qualitative study involving a convenience sample of 13 bereaved carers recruited using the Northern Ireland MND Register. Data collection consisted of semi-structured interviews with the bereaved carers of patients who had died 3-24 months previously with a diagnosis of MND. Data were analysed using thematic analysis. Findings illuminated variations in relation to the levels of holistic care provided to this cohort of patients. Unmanaged respiratory and psychological symptoms caused perceived distress amongst patients. Participants' experiences additionally highlighted reluctance amongst patients with MND to engage with services such as specialist palliative care. Conversely, for those who received input from specialist palliative care services carers portrayed these services to be of great benefit to the patient. Patients with MND in Northern Ireland may have many unmet holistic care needs. Key areas that require particular focus in terms of service development include neuromuscular respiratory physiotherapy and psychological services for patients. Future research must explore an optimal model of holistic care delivery for patients with MND and how this can be effectively integrated to best meet this patient cohorts palliative care needs.


A CAD system for the automatic detection of clustered microcalcifications in digitized mammogram films.
Clusters of microcalcifications in mammograms are an important early sign of breast cancer. This paper presents a computer-aided diagnosis (CAD) system for the automatic detection of clustered microcalcifications in digitized mammograms. The proposed system consists of two main steps. First, potential microcalcification pixels in the mammograms are segmented out by using mixed features consisting of wavelet features and gray level statistical features, and labeled into potential individual microcalcification objects by their spatial connectivity. Second, individual microcalcifications are detected by using a set of 31 features extracted from the potential individual microcalcification objects. The discriminatory power of these features is analyzed using general regression neural networks via sequential forward and sequential backward selection methods. The classifiers used in these two steps are both multilayer feedforward neural networks. The method is applied to a database of 40 mammograms (Nijmegen database) containing 105 clusters of microcalcifications. A free-response operating characteristics (FROC) curve is used to evaluate the performance. Results show that the proposed system gives quite satisfactory detection performance. In particular, a 90% mean true positive detection rate is achieved at the cost of 0.5 false positive per image when mixed features are used in the first step and 15 features selected by the sequential backward selection method are used in the second step. However, we must be cautious when interpreting the results, since the 20 training samples are also used in the testing step.


Ti plasmid and chromosomal ornithine catabolism genes of Agrobacterium tumefaciens C58.
The pTiC58 plasmid noc genes of Agrobacterium tumefaciens C58 code for nopaline oxidase (nocC), nopaline permease (nocP), the inducible periplasmic protein n1 (nocB), and a function(s) required for ornithine catabolism (nocA). In addition, strains C58 and Ach-5 of A. tumefaciens have chromosomal ornithine catabolism genes. The chromosomal orc gene codes for ornithine dehydrogenase. Strain C58 is normally orc, but orc+ mutants can be selected. We have characterized both chromosomal orc and pTiC58 nocA plasmid genes. Complementation of most chromosomal orc mutants by pTiC58 restored growth on both nopaline and L-ornithine but did not restore ornithine dehydrogenase activity. We conclude that ornithine is an intermediate of nopaline degradation and that the Ti plasmid and chromosome both code for ornithine-degradative enzymes. A model for nopaline catabolism is presented.


A Review of the Parasite Fauna of the Black-Bellied Pangolin, Phataginus tetradactyla LIN. (Manidae), From Central Africa with the Description of Intraproboscis sanghae n. gen., n. sp. (Acanthocephala: Gigantorhynchidae).
A new archiacanthocephalan in the family Gigantorhynchidae, Intraproboscis sanghae n. gen., n. sp. is described from females collected from the African black-bellied pangolin Phataginus tetradactyla Linn. (Manidae) in the Central African Republic. A dichotomous key to the genera of Gigantorhynchidae is provided. The specimens presented are distinct from those of the genus Gigantorhynchus Hamann, 1892 that have only 1 or 2 circles of hooks (crowns) at the apical end of the proboscis and are found in South American mammals, except for Gigantorhynchus pesteri Tadros, 1966 from baboons in Rhodesia (Zimbabwe), Africa (Amin, 2013). They superficially resemble those of the other gigantorhynchid genus Mediorhynchus Van Cleave, 1916, especially in the organization of the truncate-cone proboscis and the position of the receptacle. Species of Mediorhynchus are bird parasites. The new genus, Intraproboscis, now the third genus in Gigantorhynchidae; however, is distinguished from Mediorhynchus by having a simple proboscis receptacle that is completely suspended within the proboscis, the passage of the retractor muscles through the receptacle into the body cavity posteriorly, absence of neck, and presence of a parareceptacle structure (first finding in the Archiacanthocephala) and a uterine vesicle; among other features, including the differential dorsoventral thickness of the body wall. The receptacle in Mediorhynchus is complex, with many accessory muscles and retractor muscles passing into the body cavity dorsally and ventrally. Our specimens reached 180 mm in length and the proboscis had 34-36 rows of 6-7 ventrally lamellated, rooted hooks each anteriorly, and 15-17 spinelike hooks each posteriorly. Micropores extended into the anterior and posterior proboscis and energy dispersive x-ray analysis (EDXA) of anterior hooks showed high levels of calcium and phosphorus but negligible traces of sulfur. Spinelike hooks in the posterior proboscis had lower levels of Ca and P and slightly higher levels of S. Molecular and phylogenetic analyses based on the 18S rDNA gene placed I. sanghae in a clade with the archiacanthocephalans Mediorhynchus, Moniliformis, Macracanthorhynchus, Oncicola, and Oligacanthorhynchus.


Development of a harmonized patient-reported outcome questionnaire to assess myelofibrosis symptoms in clinical trials.
Along with reducing spleen size, relieving symptom severity is a key objective of the treatment of myelofibrosis (MF). Several questionnaires have been developed for patient self-report of MF symptoms in clinical trials and each includes unique instructions, items, and/or response scales. This variability in questionnaire content increases uncertainty; it is unclear which questionnaire is the most appropriate for assessing MF symptoms and it makes comparisons across trials difficult. The Patient-Reported Outcome (PRO) Consortium's MF Working Group (WG) was established to review existing MF symptom questionnaires and to develop a harmonized, consensus-based PRO questionnaire for use in future MF trials. The WG focused on the seven core symptoms of MF: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety, and bone pain. The resulting Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) asks respondents to report symptom severity at its worst for each of the seven items on a 0 (Absent) to 10 (Worst Imaginable) numeric rating scale. The MFSAF v4.0, for which there are 24-h and 7-day recall formats, will be maintained and licensed by the Critical Path Institute and made publicly available for use in future clinical trials.


The effect of the swaddling method on stress levels in newborns administered nasal CPAP.
This study aims to investigate the effects of the swaddling method on the stress levels in newborns receiving nasal continuous positive airway pressure (nCPAP). The study was conducted between 1 June 2022 and 1 October 2022 with 40 newborns who underwent nCPAP in the second-level Neonatal Intensive Care Unit (NICU) of a city hospital in the Central Anatolia Region of Turkey. Data were collected using a descriptive form, including the characteristics of newborns, a patient follow-up chart, and the Newborn Stress Scale (NSS). The descriptive form, the patient follow-up chart, and the NSS were completed by the researcher 30 min after the nCPAP was started and the first saliva sample was taken. The patient follow-up chart and NSS were completed 30 min after applying the swaddling method and the second saliva sample was collected. The data were analyzed using IBM SPSS Statistics 25.0 package software and presented with number, percentage, mean, standard deviation, min-max, and t-test. The study found that the mean score of the NSS after the intervention (3.52 ± 2.57) was lower than that before the intervention (10.02 ± 2.05) (p < 0.05). The mean saliva cortisol levels of the newborns after the intervention (4.99 ± 1.89) were lower than before the intervention (5.51 ± 1.65) (p < 0.05). The mean heart (135.50 ± 14.15) and respiratory rates (68.07 ± 10.16) of the newborns after the intervention were lower than those before the intervention (140.82 ± 18.11; 72.95 ± 9.06, respectively) (p < 0.05). There was no difference between the mean oxygen saturation of newborns before and after the intervention (p > 0.05). The study showed that the swaddling method played a role in reducing the stress levels in newborns who underwent nCPAP. It is recommended that randomized controlled trials examining the effect of swaddling on the stress levels of newborns who underwent nCPAP be conducted.


The impact of capsaicin intake on risk of developing gastric cancers: a meta-analysis.
Reported associations of capsaicin with gastric cancer development have been conflicting. Here, we examine 10 published articles that explore these associations using 2,452 cases and 3,996 controls. We used multiple search strategies in MEDLINE through PubMed to seek for suitable articles that had case-control design with gastric cancer as outcome. The outcomes of our study shows protection (odds ratio [OR] 0.55, P = 0.003) and susceptibility (OR 1.94, P = 0.0004), both significant with low and medium-high intake of capsaicin, respectively, although under relatively heterogeneous conditions (P(heterogeneity) = <0.0001). Outlier analysis resulted in loss of overall heterogeneity (P = 0.14) without affecting the pooled ORs. Among the subgroups, low intake elicited protection in both Korean (OR 0.37) and Mexican (OR 0.63) populations while high intake rendered these subgroups susceptible (OR 2.96 and OR 1.57, respectively). These subgroup values were highly significant (P = 0.0001-0.01) obtained in heterogeneous conditions (P(heterogeneity) < 0.0001-0.04). The homogeneous (P(heterogeneity) = 0.27-0.37) H. pylori (OR 0.60 and 1.69) effects were highly significant (P < 0.001) in the low and medium-high intake analyses, respectively. Given outcomes from the tests of interaction, high capsaicin intake is significantly different from the protection that low consumption offers. This meta-analysis implies moderation in capsaicin consumption in order to derive its protective benefits.


[New phages of a polylysogenic culture of Actinomyces griseus].
The culture of Actinomyces griseus 15 was found to have a more complicated phage composition than it was supposed earlier. A new virulent mutant B has been isolated, which differs by its properties from the phage of Act. griseus 15, type I, isolated earlier. Phage lysates of the virulent mutants originating from different temperate phages of Act. griseus 15. Therefore, the culture of Act. griseus 15 is polylysogenic, defective lysogenic and contains at least three different phages.


Effect of transnasal insufflation on sleep disordered breathing in acute stroke: a preliminary study.
Sleep disordered breathing (SDB) is frequent in acute stroke patients and is associated with early neurologic worsening and poor outcome. Although continuous positive airway pressure (CPAP) effectively treats SDB, compliance is low. The objective of the present study was to assess the tolerance and the efficacy of a continuous high-flow-rate air administered through an open nasal cannula (transnasal insufflation, TNI), a less-intrusive method, to treat SDB in acute stroke patients. Ten patients (age, 56.8 ± 10.7 years), with SDB ranging from moderate to severe (apnea-hypopnea index, AHI, >15/h of sleep) and on a standard sleep study at a mean of 4.8 ± 3.7 days after ischemic stroke (range, 1-15 days), were selected. The night after, they underwent a second sleep study while receiving TNI (18 L/min). TNI was well tolerated by all patients. For the entire group, TNI decreased the AHI from 40.4 ± 25.7 to 30.8 ± 25.7/h (p = 0.001) and the oxygen desaturation index >3% from 40.7 ± 28.4 to 31 ± 22.5/h (p = 0.02). All participants except one showed a decrease in AHI. The percentage of slow-wave sleep significantly increased with TNI from 16.7 ± 8.2% to 22.3 ± 7.4% (p = 0.01). There was also a trend toward a reduction in markers of sleep disruption (number of awakenings, arousal index). TNI improves SDB indices, and possibly sleep parameters, in stroke patients. Although these changes are modest, our findings suggest that TNI is a viable treatment alternative to CPAP in patients with SDB in the acute phase of ischemic stroke.


Risk of hospital-acquired legionnaires' disease in cities using monochloramine versus other water disinfectants.
To measure the association between the disinfection of municipal drinking water with monochloramine and the occurrence of hospital-acquired legionnaires' disease (LD). One hundred sixty-six U.S. hospitals. Survey of 459 members of the Society for Healthcare Epidemiology of America (SHEA) for hospital features; endemic- and outbreak-related, hospital-acquired LD; the source of the hospital water supply; and the methods of disinfection used by the hospitals and municipal water treatment plants. SHEA members representing 166 (36%) of 459 hospitals responded; 33 (20%) reported one or more episodes of hospital-acquired LD during the period from 1994 to 1998 and 23 (14%) reported an outbreak of hospital-acquired LD during the period from 1989 to 1998. Hospitals with an occurrence of hospital-acquired LD had a higher census (median, 319 vs 221; P = .03), more acute care beds (median, 500 vs 376; P = .04), and more intensive care unit beds (median, 42 vs 24; P = .009) than did other hospitals. They were also more likely to have a transplant service (74% vs 42%; P = .001) and to perform surveillance for hospital-acquired disease (92% vs 61%; P = .001). After adjustment for the presence of a transplant program and surveillance for legionnaires' disease, hospitals supplied with drinking water disinfected with monochloramine by municipal plants were less likely to have sporadic cases or outbreaks of hospital-acquired LD (odds ratio, 0.20; 95% confidence interval, 0.07 to 0.56) than were other hospitals. Water disinfection with monochloramine by municipal water treatment plants significantly reduces the risk of hospital-acquired LD.