Risk of ischaemic and haemorrhagic stroke in Chinese undergoing percutaneous coronary intervention treated with potent P2Y12 inhibitor versus clopidogrel.
Stroke after acute coronary syndrome (ACS) can be devastating. It is uncertain whether the risks of ischaemic stroke or intracranial haemorrhage (ICH) are associated with different choices of P2Y12 inhibitors (potent P2Y12 inhibitors such as ticagrelor and prasugrel vs clopidogrel). Even though East Asians are known to have different thrombotic and haemorrhagic profiles from Caucasians, data on Chinese patients are sparse. This was a retrospective cohort study conducting in Chinese patients with ACS who underwent first-ever percutaneous coronary intervention from 14 hospitals in Hong Kong between 2010 and 2017. The primary efficacy endpoint was ischaemic stroke. The secondary efficacy endpoint was a composite outcome of thrombotic events including all-cause mortality, non-fatal myocardial infarction and ischaemic stroke. The primary safety endpoint was ICH. The secondary safety endpoint was a composite of major bleeding events. After adjustment of baseline characteristics by 1:1 propensity score matching, a total of 6220 patients (3110 on each group) were analysed. Compared with clopidogrel, potent P2Y12 inhibitors were associated with a lower risk of ischaemic stroke (HR 0.57; 95% CI 0.37 to 0.87; p=0.008) and a lower risk of thrombotic events (HR 0.77; 95% CI 0.66 to 0.90; p=0.001). Potent P2Y12 inhibitor was associated with similar risk of ICH (HR 0.65; 95% CI 0.34 to 1.25, p=0.20) and major bleeding (HR 0.83; 95% CI 0.68 to 1.01, p=0.069). Potent P2Y12 inhibitors were associated with a lower adjusted risk of ischaemic stroke and thrombotic events, compared with clopidogrel. The risks of ICH and major bleeding were similar.


Adopting permanent His bundle pacing: learning curves and medium-term outcomes.
This study aims to determine procedural characteristics, acute success rates, and medium-term outcomes of consecutive patients undergoing His bundle pacing (HBP); and learning curves of experienced electrophysiologists adopting HBP. Consecutive HBP patients at three hospitals were recruited. Clinical characteristics, acute procedural details, and medium-term outcomes were extracted from electronic medical records. Two hundred and thirty-three patients [mean age 74.6 ± 10.1 years, 48% female, 68% narrow QRS, 71% normal left ventricular ejection fraction (LVEF), 55.8% atrioventricular block] underwent HBP. Acute procedural success was 81.1% (mean procedural and fluoroscopic times of 105.5 ± 36.5 and 13.8 ± 9.3 min). Broad QRS was associated with lower HBP success (odds ratio 0.39, P = 0.02). Fluoroscopic and procedural times decreased and plateaued after 30-40 cases per operator. Implant HBP threshold was 1.3 ± 0.7 V at 1.0 ± 0.2 ms and R wave was 5.0 ± 3.9 mV. During follow-up, loss of HBP occurred in a further 12.4% and 11.3% of patients experienced a ≥1 V increase in HBP threshold. Five (2.6%) patients required HBP revision for pacing difficulties. About 8.6% of patients had a >50% decrease in R wave but lead revision for sensing issues was not necessary. On an intention to treat basis, 56.7% of patients in whom HBP was attempted had persisting HBP capture and thresholds of <2 V. Physicians adopting HBP should be cognizant of the learning curve and preferentially select non-dependent patients with normal QRS and LVEF, to minimize risk of lead revision. Further rises in HBP threshold may increase battery drain and need for reoperations, important considerations when choosing HBP for cardiac resynchronization therapy.


Lowering caveolin-1 expression in human vascular endothelial cells inhibits signal transduction in response to shear stress.
Vascular endothelial cells have an extensive response to physiological levels of shear stress. There is evidence that the protein caveolin-1 is involved in the early phase of this response. In this study, caveolin-1 was downregulated in human endothelial cells by RNAi. When these cells were subjected to a shear stress of 15 dyn/cm(2) for 10 minutes, activation of Akt and ERK1/2 was significantly lower than in control cells. Moreover, activation of Akt and ERK1/2 in response to vascular endothelial growth factor was significantly lower in cells with low levels of caveolin-1. However, activation of integrin-mediated signaling during cell adhesion onto fibronectin was not hampered by lowered caveolin-1 levels. In conclusion, caveolin-1 is an essential component in the response of endothelial cells to shear stress. Furthermore, the results suggest that the role of caveolin-1 in this process lies in facilitating efficient VEGFR2-mediated signaling.


Cost-Effectiveness of First-Line Sevelamer and Lanthanum versus Calcium-Based Binders for Hyperphosphatemia of Chronic Kidney Disease.
Phosphate binders are used to treat hyperphosphatemia among patients with chronic kidney disease (CKD). To conduct an economic evaluation comparing calcium-free binders sevelamer and lanthanum with calcium-based binders for patients with CKD. Effectiveness data were obtained from a recent meta-analysis of randomized trials. Effectiveness was measured as life-years gained and translated to quality-adjusted life-years (QALYs) using utility weights from the literature. A Markov model consisting of non-dialysis-dependent (NDD)-CKD, dialysis-dependent (DD)-CKD, and death was developed to estimate the incremental costs and effects of sevelamer and lanthanum versus those of calcium-based binders. A lifetime horizon was used and both costs and effects were discounted at 1.5%. All costs are presented in 2015 Canadian dollars from the Canadian public payer perspective. Results of probabilistic sensitivity analysis were presented using cost-effectiveness acceptability curves. Sensitivity analyses were conducted for risk pooling methods, omission of dialysis costs, and persistence of drug effects on mortality. Sevelamer resulted in an incremental cost-effectiveness ratio of $106,522/QALY for NDD-CKD and $133,847/QALY for DD-CKD cohorts. Excluding dialysis costs, sevelamer was cost-effective in the NDD-CKD cohort ($5,847/QALY) and the DD-CKD cohort ($11,178/QALY). Lanthanum was dominated regardless of whether dialysis costs were included. Existing evidence does not clearly support the cost-effectiveness of non-calcium-containing phosphate binders (sevelamer and lanthanum) relative to calcium-containing phosphate binders in DD-CKD patients. Our study suggests that sevelamer may be cost-effective before dialysis onset. Because of the remaining uncertainty in several clinically relevant outcomes over time in DD-CKD and NDD-CKD patients, further research is encouraged.


Inhibition of the NADPH Oxidase Pathway Reduces Ferroptosis during Septic Renal Injury in Diabetic Mice.
Obesity and type 2 diabetes mellitus (DM) contribute to a higher mortality rate in patients with septic acute kidney injury (AKI) during sepsis. Reactive oxygen species (ROS) is the major injury factor for sepsis. This study was aimed at exploring the potential therapeutic drug for septic AKI targeting on ROS. A murine septic AKI model was established in both wild-type and high-fat diet-fed (HFD) mice. NADPH oxidase inhibitor Vas2870 was used in vivo to explore the role of NADPH oxidase in ROS release in septic AKI in diabetic mice. Ferrostatin-1 was administered to investigate the role of ferroptosis in ROS accumulation during NADPH oxidase activating in septic AKI in diabetic mice. Compared to chow diet-fed mice, HFD diabetic mice which were subjected to LPS exhibited aggravated renal function (blood urea nitrogen, creatinine clearance, and serum cystatin C) and oxidative stress (malondialdehyde, 4-HNE, ROS, 8-OHdG, and NADPH oxidase), thus resulting in a higher mortality rate. Septic renal injury was significantly attenuated by the ferroptosis inhibitor Fer-1 in HFD-challenged mice. Furthermore, ferroptosis accumulation and related protein expression (ASCL4, FTH1, and GPX4) were altered by LPS stimulation in HFD-challenged mice and suppressed by NADPH oxidase inhibition via Vas2870 in vivo. In summary, NADPH inhibition restored septic renal function from injury by suppressing ferroptosis accumulation in HFD-challenged mice. These results suggest that targeting NADPH-mediated ROS release and ferroptosis accumulation is a novel therapeutic strategy to protect the kidney from septic injury in patients with obesity and type 2 DM.


Microstructures of GaN thin films grown on graphene layers.
Plan-view and cross-sectional transmission electron microscopy images show the microstructural properties of GaN thin films grown on graphene layers, including dislocation types and density, crystalline orientation and grain boundaries. The roles of ZnO nanowalls and GaN intermediate layers in the heteroepitaxial growth of GaN on graphene, revealed by cross-sectional transmission electron microscopy, are also discussed.


Validation of morphometric analyses of small-intestinal biopsy readouts in celiac disease.
Assessment of the gluten-induced small-intestinal mucosal injury remains the cornerstone of celiac disease diagnosis. Usually the injury is evaluated using grouped classifications (e.g. Marsh groups), but this is often too imprecise and ignores minor but significant changes in the mucosa. Consequently, there is a need for validated continuous variables in everyday practice and in academic and pharmacological research. We studied the performance of our standard operating procedure (SOP) on 93 selected biopsy specimens from adult celiac disease patients and non-celiac disease controls. The specimens, which comprised different grades of gluten-induced mucosal injury, were evaluated by morphometric measurements. Specimens with tangential cutting resulting from poorly oriented biopsies were included. Two accredited evaluators performed the measurements in blinded fashion. The intraobserver and interobserver variations for villus height and crypt depth ratio (VH:CrD) and densities of intraepithelial lymphocytes (IELs) were analyzed by the Bland-Altman method and intraclass correlation. Unevaluable biopsies according to our SOP were correctly identified. The intraobserver analysis of VH:CrD showed a mean difference of 0.087 with limits of agreement from -0.398 to 0.224; the standard deviation (SD) was 0.159. The mean difference in interobserver analysis was 0.070, limits of agreement -0.516 to 0.375, and SD 0.227. The intraclass correlation coefficient in intraobserver variation was 0.983 and that in interobserver variation 0.978. CD3(+) IEL density countings in the paraffin-embedded and frozen biopsies showed SDs of 17.1% and 16.5%; the intraclass correlation coefficients were 0.961 and 0.956, respectively. Using our SOP, quantitative, reliable and reproducible morphometric results can be obtained on duodenal biopsy specimens with different grades of gluten-induced injury. Clinically significant changes were defined according to the error margins (2SD) of the analyses in VH:CrD as 0.4 and in CD3(+)-stained IELs as 30%.


The MeLiM Minipig: An Original Spontaneous Model to Explore Cutaneous Melanoma Genetic Basis.
Melanoma is the deadliest skin cancer and is a major public health concern with a growing incidence worldwide. As for other complex diseases, animal models are needed in order to better understand the mechanisms leading to pathology, identify potential biomarkers to be used in the clinics, and eventually molecular targets for therapeutic solutions. Cutaneous melanoma, arising from skin melanocytes, is mainly caused by environmental factors such as UV radiation; however a significant genetic component participates in the etiology of the disease. The pig is a recognized model for spontaneous development of melanoma with features similar to the human ones, followed by a complete regression and a vitiligo-like depigmentation. Three different pig models (MeLiM, Sinclair, and MMS-Troll) have been maintained through the last decades, and different genetic studies have evidenced a complex inheritance of the disease. As in humans, pigmentation seems to play a prominent role, notably through MC1R and MITF signaling. Conversely, cell cycle genes as CDKN2A and CDK4 have been excluded as predisposing for melanoma in MeLiM. So far, only sparse studies have focused on somatic changes occurring during oncogenesis, and have revealed major cytological changes and a potential dysfunction of the telomere maintenance system. Finally, the spontaneous tumor progression and regression occurring in these models could shed light on the interplay between endogenous retroviruses, melanomagenesis, and adaptive immune response.


[Opiate receptor binding of naloxone in the rat brain: effect of sodium ions].
The binding levels and opiate receptor binding parameters were determined for 3H-naloxone in rat brain in the presence of NaCl added in vitro. An addition of NaCl at concentrations of 5-35 mM to the reaction medium caused an increase in the level of the antagonist receptor binding. The maximal level of 3H-naloxone reception activation was observed in the presence of 10-20 mM NaCl and was, on the average, 25%. Both the increase in the NaCl dose in vitro and its decrease caused a gradual diminution of the Na+ effect. An analysis of opiate receptor saturation with 3H-naloxone revealed that the label interacted with one type of the binding sites irrespective of NaCl concentration. The affinity of receptor binding sites for 3H-naloxone increased already at NaCl concentration of 2.5 mM. In contrast, the apparent maximal number of binding sites did not change after NaCl addition at concentrations which coincided with the intracellular Na+ level but was decreased with an increase (up to 50-100 mM) in NaCl present in the reaction mixture. The results obtained point to the existence of two different binding sites that are coupled with the 3H-naloxone reactive opiate receptor.


PEBP2-beta/CBF-beta-dependent phosphorylation of RUNX1 and p300 by HIPK2: implications for leukemogenesis.
The heterodimeric transcription factor RUNX1/PEBP2-beta (also known as AML1/CBF-beta) is essential for definitive hematopoiesis. Here, we show that interaction with PEBP2-beta leads to the phosphorylation of RUNX1, which in turn induces p300 phosphorylation. This is mediated by homeodomain interacting kinase 2 (HIPK2), targeting Ser(249), Ser(273), and Thr(276) in RUNX1, in a manner that is also dependent on the RUNX1 PY motif. Importantly, we observed the in vitro disruption of this phosphorylation cascade by multiple leukemogenic genetic defects targeting RUNX1/CBFB. In particular, the oncogenic protein PEBP2-beta-SMMHC prevents RUNX1/p300 phosphorylation by sequestering HIPK2 to mislocalized RUNX1/beta-SMMHC complexes. Therefore, phosphorylation of RUNX1 appears a critical step in its association with and phosphorylation of p300, and its disruption may be a common theme in RUNX1-associated leukemogenesis.


Fast determination of the release degree of compound sulfamethoxazole tablets by using circulation release system combined with ultraviolet spectral net analyte signal method.
Based on ultraviolet spectral net analyte signals, this research has studied the determination of the two effective components, sulfamethoxazole (SMZ) and trimethoprim (TMP), contained in compound sulfamethoxazole tablets in acid environment. The linear ranges of SMZ and TMP were 0.48-7.84 microg/ml (the regression correlation coefficient r = 0.9981) and 0.12-1.5 microg/ml (r = 0.9986), the corresponding average recoveries were 99.5 and 101.0%, respectively, and the relative standard deviations were 1.87 and 3.60%, respectively. The method was simple, fast and accurate. A circulation release system for the determination of the tablet release degree has been built, and the on-line filtering and small-volume sampling could thus be carried out. Thanks to the combination of the circulation release system and the determination method of SMZ and TMP in acid environment, the determination of release degree for compound sulfamethoxazole tablets was fast and accurate, especially for the early time of rapid release.


Nursing diagnosis: educational strategy based on problem-based learning.
This study aimed to evaluate the effectiveness of a teaching strategy on nursing diagnoses based on problem-based learning in the performance of clinical reasoning and diagnostic trial of undergraduate students. Experimental study conducted in two phases: content validation of problems and implementation of educational strategy. The results showed improvement in the data pooling ability of students in the experimental group. It is concluded that the strategy put in practice exerted a positive influence.


Development of the transformational advanced professional practice model.
The purpose of this article is to describe the development of a professional practice model (PPM) for advanced practice registered nurses (APRNs). A literature review was conducted on PPMs. Simultaneous review of authoritative resources, including The National Organization of Nurse Practitioner Faculties (NONPF) and the Licensure, Accreditation, Certification and Education (LACE) Consensus Model, was performed. An expert panel was established to validate the transformational advanced professional practice (TAPP) model. APRNs are relied upon by organizations to provide leadership in the delivery of high-quality, cost-effective health care while improving access and eliminating preventable morbidities. Existing models fail to fully capture the professional scope of practice for APRNs. The TAPP model serves as a framework to guide professional development and mentorship of APRNs in seven domains of professional practice (DOPP). To meet the Institute of Medicine's recommendations for the future of nursing, APRNs should practice to the fullest extent of their education and training. Providing clarification regarding the DOPP of the APRN role is needed to standardized professional practice. The TAPP model is an inspiring blueprint that allows APRNs to model the way by delivering comprehensive health care in seven DOPP.


Mouse Nerve Growth Factor Injection and Progression Rate in Patients With Amyotrophic Lateral Sclerosis: An Observational Study.
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease with no curative treatment up to now. This study aims to analyze ALS progression of patients treated with mouse nerve growth factor (mNGF), as well as the effects, side effects, and adverse events of the therapy. A retrospective, observational study was performed including 94 patients with ALS from July 2020 to July 2021. Thirty-two of them were treated with at least one course of mNGF on a regular riluzole use, and the rest 62 were treated with riluzole only. The declining rates of body mass index (BMI) and ALS Functional Rating Scale-Revised (ALSFRS-R) scores were compared between the two groups to indicate ALS progression. No significant differences in ALS progression indicated by the declining rates of BMI and ALSFRS-R score were observed between the two cohorts. ALS progression before and after the first treatment course of mNGF also showed no discernible difference. However, we noticed a moderate 62.7 and 25.1% reduction in the declining rate of BMI and ALSFRS-R motor subscore when comparing mNGF + riluzole treatment to riluzole only. The mNGF treatment was overall safe and well-tolerated, and a rare case of diarrhea was reported after mNGF injection. Our study revealed that mNGF treatment was overall safe and well-tolerated in patients of ALS. Application of mNGF combined with regular riluzole treatment had no significant clinical effects on delaying ALS progression. Prospective cohort studies and randomized clinical trials based on larger cohorts and longer follow-up times are needed to make a more convincing conclusion.


Phonological processing and the role of strategy in silent reading: behavioral and electrophysiological evidence.
To examine the contribution of phonological processing in silent reading, 51 native English speakers made decisions about targets presented either in word pairs or in sentences. The target words were homophonically (plain-plane), orthographically (plane-place), or semantically (plane-jet) related. N200 was enhanced only to homophonic targets, suggesting the use of phonological information in silent reading. Memory load did not affect the N200 amplitude. N400 was enhanced to all semantically incongruent words and was larger in the word pair condition. Reaction times were influenced by both experimental condition and target relationships; homophonic stimuli elicited the fastest RTs in the word pair condition and the slowest RTs in the sentence condition, suggesting the use of different strategies. Thus, ERP components and behavioral responses registered different aspects of language processing.


Gastric acidity protects mice against prion infection?
The transmissible degenerative encephalopathies (TDEs) constitute a distinct group of diseases (scrapie in sheep, bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease (CJD) in humans). The causal agents are not fully characterized, but are known to be resistant to most inactivation procedures. Ruminants appear to be particularly susceptible to TDEs. The concentrations of hydrochloric acid in their digestive tracts are significantly lower than in monogastric species. The aim of the study was to examine the role of gastric acidity in the protection of mice against infection after intragastric administration of different doses of a scrapie agent. Gastric acidity levels in mice were reduced by adding ranitidine to the drinking water and the animals were observed for neurological symptoms and at sacrifice examined microscopically for spongiform lesions in the brain. The lower doses of infectious material induced disease significantly more often in mice given ranitidine compared with the controls. These data indicate that the normal levels of gastric acidity in mice protect them to some extent from infection with low doses of scrapie agent. This finding is potentially relevant to the pathogenesis of the variant form of CJD, which appears to be associated with the consumption of BSE-infected food products.


Geographic variation in rheumatoid arthritis incidence among women in the United States.
The geographic variation in rheumatoid arthritis (RA) incidence in the United States is unknown. We studied residential region from January 1, 1921, to May 31, 1976, and RA risk in a prospective cohort of women, the Nurses' Health Study. Information on state of residence was collected at baseline in 1976 (when participants were aged 30-55 years) and on state of residence at birth, at age 15 years, and at age 30 years in 1992. Among 83,546 participants reporting residence for all 4 time points, 706 incident RA cases from June 1, 1976, to May 31, 2004, were confirmed by screening questionnaire and record review for American College of Rheumatology criteria. Residential region was classified as West, Midwest, mid-Atlantic, New England, and Southeast. Multivariate Cox proportional hazards regression models were used to assess relationships between region and RA risk, adjusting for age, smoking, body mass index, parity, breastfeeding, postmenopausal status, postmenopausal hormone use, father's occupation, race, and physical activity. Analyses were performed in participants who lived in the same regions, or moved, over time. Compared with those in the West, women in New England had a 37% to 45% elevated risk of RA in multivariate models at each time point (eg, state of residence in 1976: rate ratio [RR], 1.42; 95% confidence interval [CI], 1.10-1.82). In analyses of women who lived in the same region at birth, age 15 years, and age 30 years, living in the Midwest was associated with greater risk (RR, 1.47; 95% CI, 1.05-2.05), as was living in New England (RR, 1.40; 95% CI, 0.98-2.00). Compared with living in the West at birth, age 15 years, and age 30 years, RA risk was higher in the East. In this large cohort of US women, significant geographic variation in incident RA existed after controlling for confounders. Potential explanations include regional variation in behavioral factors, climate, environmental exposures, RA diagnosis, and genetic factors.


Exploring partial control of chaotic systems.
In this paper we make a thorough exploration of the technique of partial control of chaotic systems. This control technique allows one to keep the trajectories of a dynamical system close to a chaotic saddle even if the control applied is smaller than the effects of environmental noise in the system, provided that the chaotic saddle is due to the existence of a horseshoelike mapping in phase space. We state this here in a mathematically precise way using the Conley-Moser conditions, and we prove that they imply that our partial control strategy can be applied. We also give an upper bound of the control-noise ratio needed to achieve this goal, and we describe how this technique can be applied for large noise values. Finally, we study in detail the effect of imperfect targeting in our control technique. All these results are illustrated numerically with the paradigmatic Hénon map.


Dominance and social interaction patterns in brown capuchin monkey (Cebus [Sapajus] apella) social networks.
Strong, stable social bonds in primates are characterized by high levels of social affiliation, low levels of aggression, minimal stress, and affiliative reciprocity within the dyad. In relatively well-studied catarrhine monkeys, these bonds tend to form most frequently between kin, animals close in age, and animals close in rank. This results in patterns of affiliation in which kin, similarly aged animals, and like-ranked animals tend to affiliate and patterns of aggression and submission where animals tend to aggress more toward nonkin and closely ranked animals, and submit more toward distantly ranked animals. However, literature on how affiliative and agonistic relationships are organized in platyrrhine primate species like brown capuchin monkeys is limited and conflicting. In this study, we used social network analyses to characterize how age, sex, maternal kinship, and dominance rank relate to the patterns of submissive, aggressive, contact, and grooming interactions in a group of captive brown capuchin monkeys. Like catarrhine monkeys, brown capuchin monkeys showed a steep linear dominance hierarchy, tended to affiliate with kin, similarly aged animals, and like-ranked animals, and tended to aggress more toward nonkin. However, our monkeys showed a pattern of affiliation and grooming down the hierarchy that is inconsistent with grooming up the hierarchy patterns often seen in catarrhine monkey groups, suggesting that brown capuchins do not compete for access to higher ranking social partners. Higher ranking monkeys were most central to the aggression network, and lower ranking monkeys were most central to the submission network. Mid-ranking monkeys were the most central to the contact network, suggesting that they may play an important role in the affiliative cohesion of the group. These results inform our understanding of brown capuchin social behavior specifically, and of how demographic factors relate to social organization in platyrrhine primates generally.


Gender Specifics of Healthy Ageing in Older Age as Seen by Women and Men (70+): A Focus Group Study.
(1) The rising proportion of older adults in the population represents a challenge for the healthcare system. Women and men age differently. This study aims to examine gender-specific characteristics of health in old age from male and female perspectives. (2) Two focus groups were formed in this qualitative study of older (70+) women (n = 10) and men (n = 8) in accordance with the theoretical framework of the World Health Organization (WHO) on healthy ageing determinants. The data were audio recorded and fully transcribed. Qualitative content analysis was performed using MAXQDA. (3) In both focus groups (average age: women 77.1 years, men 74.9 years), gender-specific characteristics regarding healthy ageing were discussed. Women focused on healthy eating, while men focused on an active lifestyle and meaningful activities. Physical and social activities were considered as important for healthy ageing in both groups. (4) Important gender-specific characteristics of health in old age were identified and recommendations for gender-unspecific and gender-specific recommendations were derived. The results provide important information for promoting and maintaining health in old age. Women and men show both similarities and differences in terms of health-related needs and individual experiences. We suggest gender-specific features in nutrition and health programs for older adults.


Tailoring Multi-omics to Inflammatory Bowel Diseases: All for One and One for All.
Inflammatory bowel disease [IBD] has a multifactorial origin and originates from a complex interplay of environmental factors with the innate immune system at the intestinal epithelial interface in a genetically susceptible individual. All these factors make its aetiology intricate and largely unknown. Multi-omic datasets obtained from IBD patients are required to gain further insights into IBD biology. We here review the landscape of multi-omic data availability in IBD and identify barriers and gaps for future research. We also outline the various technical and non-technical factors that influence the utility and interpretability of multi-omic datasets and thereby the study design of any research project generating such datasets. Coordinated generation of multi-omic datasets and their systemic integration with clinical phenotypes and environmental exposures will not only enhance understanding of the fundamental mechanisms of IBD but also improve therapeutic strategies. Finally, we provide recommendations to enable and facilitate generation of multi-omic datasets.


Interest in multipurpose prevention technologies to prevent HIV/STIs and unintended pregnancy among young women in the United States.
High rates of sexually transmitted infections (STIs) and unintended pregnancy suggest a role for multipurpose prevention technologies (MPTs) designed to combine contraception and infection prophylaxis into one unified method. This study aims to determine factors associated with interest in MPTs among US women. We administered a national cross-sectional survey via MTurk. Eligibility criteria included female gender, age 18-29 years, residence in the USA, and sexual activity with a male partner in the past three months. In total, 835 surveys were suitable for analysis. Bivariable and multivariable logistic regressions were performed to determine factors associated with interest in MPTs. Eighty-three percent of women were interested in MPTs. Factors associated with interest included oral sex in the past three months (aOR 1.87, 95% CI 1.07, 3.53), recent use of oral contraceptive pills (OCPs; aOR 1.78, 95% CI 1.08, 2.93), HIV test within one year (aOR 2.10, 95% CI 1.29, 3.40), and increased STI worry score (aOR 1.98, 95% CI 1.36, 2.86). No use of contraception in the past three months was associated with decreased interest in MPTs (aOR 0.31, 95% CI 0.17, 0.58). HIV risk factors including race were not associated with MPT interest. Our data show that young, sexually active, US women are interested in MPTs. Women who used contraception, specifically OCPs, or evidenced concern for infection were most likely to be interested in such a product. Women reporting unsafe sexual habits were less likely to be interested, highlighting the importance of HIV/STI prevention education. Women in the USA are interested in multipurpose prevention technologies, particularly those women who currently use contraception or are concerned about their risk of infection. Our results emphasize the importance of moving forward with MPT development as well as continued HIV/STI prevention education.


[Expression of p27 and TGF-beta in rat kidney with unilateral ureteral obstruction and the relationship between TGF-beta and p27].
To explore the expression of p27 and the changes of TGF-beta in the renal tubule on the process of renal interstitial fibrosis caused by unilateral ureteral obstruction (UUO) in rats and to investigate the relationship between TGF-beta and p27 in renal interstitial fibrosis rats. Sixty rats were randomly divided into sham-operated group (SOR) and UUO group. Ten rats from each group were sacrificed on days 7, 14 and 21 after operation respectively. The renal pathological changes were dynamically observed by HE . The expression and dynamic changes of p27 were detected by immunohistochemistry. The levels of p27 mRNA and TGF-beta mRNA were detected by RT-PCR. The expression of p27 in renal tubular epithelial cells and p27mRNA was strongly positive in SOR group. With the aggravation of interstitial fibrosis, the expression of p27 gradually decreased in UUO group while the expression of TGF-beta increased. There was a negative correlation between TGF-beta and p27. P27 is involved in the fibrosis of renal mesenchyme in rats with UUO. The mechanism of TGF-beta accelerating fibrosis may relate to the reduction of p27 expression in UUO rats.


Distribution of Cytosolic mRNAs Between Polysomal and Ribonucleoprotein Complex Fractions in Alfalfa Embryos : Stage-Specific Translational Repression of Storage Protein Synthesis during Early Somatic Embryo Development.
Cell-free translational and northern blot analyses were used to examine the distribution of storage protein messages in the cytoplasmic polysomal and mRNA-protein complex (mRNP) fractions during development of somatic and zygotic embryos of alfalfa (Medicago sativa cv Rangelander RL-34). No special array of messages was identified in the mRNP fraction; however, some messages were selectively enriched in either the polysome or mRNP fractions, and their distribution pattern varied quantitatively during development of the embryos. During the earliest stages of somatic embryo development, storage protein messages already were present, but there was no detectable accumulation of the proteins. Selective enrichment of messages for the 11S, 7S, and 2S storage proteins occurred in the mRNP fraction during the globular, heart, and torpedo stages of somatic embryogenesis, but the distribution pattern was shifted toward the polysomal fraction at the beginning of cotyledon development. Thus, there was translational repression of storage protein synthesis at the early stage of somatic embryo development that was relieved later. During the cotyledonary development stages in the somatic and zygotic embryos, storage protein synthesis and distribution of the messages were similar in that these specific messages were predominantly in the polysomal fraction.


Phenol hydroxylase from yeast. A model for phenol binding and an improved purification procedure.
The binding of phenol to phenol hydroxylase was studied by equilibrium dialysis, spectrophotometric titration and by steady-state kinetics. A binding model with two identical, negatively cooperative, effector/substrate-binding sites per enzyme dimer is proposed. The spectral perturbation caused by phenol and the kinetics of the overall reaction were analysed with relation to the enzyme-phenol complexes of the binding model. The main part of the spectral perturbation as well as of the increase in NADPH oxidation rate was achieved by one molecule of phenol bound per enzyme dimer. The properties of different enzyme-phenol complexes, in terms of spectral changes, hydroxylase activity, oxidase activity and substrate inhibition are discussed. A new purification procedure is described.


[Neurologic complications of brain radiotherapy: contribution of experimental studies].
Cerebral complications of radiotherapy may occur in an acute, early or semi-delayed or delayed form. The mechanism of these complications are poorly understood. The main clinical aspects of radiation-induced cerebral damage are reviewed, together with results of experimental studies following cerebral irradiation with conventional doses.


Interleukin-2: clinical applications.
Interleukin-2 (IL-2) is a promising immunotherapeutic agent for the treatment of metastatic melanoma, acute myelogenous leukemia, and metastatic renal cell carcinoma. While high-dose IL-2 regimens have shown clinical benefit in the treatment of melanoma and renal cell carcinoma, serious dose-limiting toxicities have limited their clinical use in a broader group of patients. Low-dose IL-2 therapy has produced disappointing clinical response rates in melanoma. While the response rates to low-dose IL-2 have been better in renal cell carcinoma, the quality of these responses relative to those seen with high-dose IL-2 therapy remains a concern. The addition of IL-2 to chemotherapeutic regimens (biochemotherapy) has been associated with overall response rates of up to 60% in patients with metastatic melanoma, but this has yet to be translated into a confirmed improvement in survival. It remains to be determined whether further modifications of IL-2-based regimens or the addition of newer agents to IL-2 will produce better tumor response and survival.


Effects of streptozotocin-induced diabetes on neurogenic inflammation of gingivomucosal tissue in rat.
It has been suggested that the unmyelinated small diameter afferent nociceptive C-fibres are impaired in diabetes mellitus. We have recently demonstrated that these fibres are the prerequisite for neurogenic inflammation induced by mechanical or chemical irritations. These experiments were designed to characterize the neurogenic inflammatory responses of gingivomucosal tissue in the early phase of experimental induced diabetes mellitus in rat. Effect of dental ligature on the gingivomucosal (GM) vascular permeability was studied in control rats and in rats pretreated with streptozotocin at d 7 and 14 following streptozotocin administration. In separate groups of control and streptozotocin diabetic rats studies were also performed to investigate the effect of local capsaicin application on GM vascular permeability on d 14. Vascular permeability was assessed by means of Evans blue extravasation. The ligature placed around the mandibular left first molar caused a significant increase vascular permeability of GM tissue on the ipsilateral side on both d 7 and 14 after the ligation in control rats. In streptozotocin diabetic rats on d 7, there was also a significant elevation of Evans blue extravasation in the tissue tested on the ligature side. However, on d 14 the ligation failed to produce any changes in Evans blue extravasation on the ipsilateral side, i.e. no difference in GM vascular permeability could be recorded between the two sides in streptozotocin diabetic rats. Topical capsaicin administration produced significant Evans blue extravasation in GM tissue of control rats compared to that observed in diabetic rats on d 14 after streptozotocin treatment. Electron microscopic and light microscopic studies demonstrated fibre degeneration of the C neurones and less inflammatory cells in streptozotocin-induced diabetes in the gingivomucosal tissue. These findings appear to indicate that the inflammatory responses induced by mechanical (dental ligature) and/or chemical irritants (topical application of capsaicin) in the gingivomucosal tissue are altered in streptozotocin diabetic rats and this alteration is due to the diabetes-induced damage to the unmyelinated C fibres.


Continued adverse trends in coronary heart disease mortality among blacks, 1980-91.
An abrupt downturn in mortality rates from coronary heart disease occurred in the United States in the mid-1960s, and for the next decade all four major sex-race groups experienced virtually identical rates of decline. Beginning around the mid-1970s, however, trends for blacks and whites began to diverge, with a deceleration in the annual fall in rates for blacks. The recent release of mortality data extending through 1991, with correction of the denominator estimates in the 1980s using the 1990 census, demonstrate a striking linearity of this trend over the entire decade. In 1989, for the first time since the category of coronary heart disease has been recorded in vital statistics, the age-adjusted death rate for it among black men exceeded that of whites. As a result of the divergent trends among men, an excess of 4,000 deaths of blacks were recorded in 1991 alone. Among women, coronary heart disease mortality was higher among blacks at the beginning of this period, and the average annual percent decline was only two-thirds that of whites. As a result, the absolute mortality gap between blacks and whites steadily increased from 19 to 33 percent (1980 to 1991). This study indicates that the factors that have led to the decline in coronary heart disease have not influenced all demographic groups equally over the last decade.


Mushroom stem cells.
Contrary to the rarity of totipotent cells in animals, almost every cell formed by a fungus can function as a "stem cell". The multicellular fruiting bodies of basidiomycete fungi consist of the same kind of filamentous hyphae that form the feeding phase, or mycelium, of the organism, and visible cellular differentiation is almost nonexistent. Mushroom primordia develop from masses of converging hyphae, and the stipe (or stem), cap, and gills are clearly demarcated within the embryonic fruiting body long before the organ expands and unfolds through water uptake and cell wall loosening. Though frequent references are made to gilled mushrooms in this article, the totipotent nature of fruiting body cells and lack of meristems is also applicable to basidiomycetes that spread their spore-producing tissues inside tubes (e.g., boletes), over spines and rippled surfaces, or form spores in cavities within the fruiting body. Even in the mature mushroom, every hypha retains its totipotency. Among animals, only sponges exhibit a similar degree of developmental flexibility, which is interesting, because these simple metazoans may be relatively close relatives of fungi.


Clinical Outcome of Eosinophilia in Patients with COVID-19: A Controlled Study.
Eosinophils can be considered as multifunctional leukocytes that contribute to various physiological and pathological processes depending on their location and activation status. There are emerging eosinophil-related considerations concerning COVID-19. Variable eosinophil counts have been reported during COVID-19. Whether these changes are related to the primary disease process or due to immunomodulation induced by the treatment has not yet been elucidated. To describe changes in the differential leukocyte counts including eosinophils, in a cohort of symptomatic patients with confirmed COVID-19 and to correlate these changes, if any, with the severity of the disease. We recorded the clinical data, lab findings, including inflammatory markers and leukocyte and differential count, course of the disease and severity score in 314 confirmed symptomatic cases of COVID-19. Laboratory tests revealed that 28.7 % (n =86) had mild eosinophilia (eosinophil count > 500 <1,500/µL). Thirty-four patients (11.3%) had elevated absolute neutrophil count (ANC) (>8,000/µL), and 7 (2.3%) had decreased ANC (< 1,500/µl). Seven patients (2.3%) had lymphopenia (<1,000/µL) and 4 (4.67%) had lymphocytosis (> 4,000/µL). C-reactive protein (CRP) was elevated in 83 patients (27.6%). Chest X-Ray changes included: increased broncho vascular markings (38%), ground-glass opacity (GGO) pneumonitis (19.3%), lobar consolidation (5%), bronchopneumonia (8.3%), nodular opacity (1%), acute respiratory distress syndrome (ARDS) (2.3%), pleural effusion (1.0%) and other atypical findings (6.6%). Patients with eosinophilia had significantly lower CRP, and lower % of GGO, lobar and bronchopneumonia and ARDS in their chest images compared to patients without eosinophilia (p: <0.05). They also had a lower requirement for a hospital stay, ICU admission, mechanical ventilation, and oxygen supplementation versus patients without eosinophilia (p: <0.05). The eosinophils count was correlated negatively with the duration of ICU admission, mechanical ventilation, and oxygen supplementation and with CRP level (r: - 0.34, -0.32, -0.61 and - 0.39, respectively) (p: < 0.01). Our study reports a relatively high prevalence of eosinophilia in symptomatic COVID-19 positive patients. Patients with eosinophilia had a lower level of CRP, milder clinical course and better disease outcomes compared to those without eosinophilia. Our findings indicated a protective role of eosinophils in mitigating the severity of inflammatory diseases through an inhibitory mechanism, as evidenced by lower CRP. This protective role of eosinophils needs to be validated by further prospective studies.


Structural differences among alkali-soluble arabinoxylans from maize (Zea mays), rice (Oryza sativa), and wheat (Triticum aestivum) brans influence human fecal fermentation profiles.
Human fecal fermentation profiles of maize, rice, and wheat bran and their dietary fiber fractions released by alkaline-hydrogen peroxide treatment (principally arabinoxylan) were obtained with the aim of identifying and characterizing fractions associated with high production of short chain fatty acids and a linear fermentation profile for possible application as a slowly fermentable dietary fiber. The alkali-soluble fraction from maize bran resulted in the highest short chain fatty acid production among all samples tested, and was linear over the 24 h fermentation period. Size-exclusion chromatography and (1)H NMR suggested that higher molecular weight and uniquely substituted arabinose side chains may contribute to these properties. Monosaccharide disappearance data suggest that maize and rice bran arabinoxylans are fermented by a debranching mechanism, while wheat bran arabinoxylans likely contain large unsubstituted xylose regions that are fermented preferentially, followed by poor fermentation of the remaining, highly branched oligosaccharides.


Using a circadian rhythms model to evaluate shift schedules.
As long as the need for shiftwork exists, so will the demand for an optimal scheduling strategy that balances the needs of both industry and the shiftworker. One aim is for schedules that require workers to be on duty during the times that they are most naturally alert and awake. Czeisler et al. (1982) developed a set of circadian rhythm based guidelines intended to aid in designing such shiftwork schedules. This paper takes research one step further by testing such empirical criteria in a mathematical setting. The two-oscillator model of free-run human circadian rhythms developed by Kronauer et al. (1982) was modified to represent the circadian rhythms of a shiftworker on a pre-selected shiftwork schedule. Numerical simulations were used to compare the circadian rhythms produced from a variety of shiftwork schedules to the free-run rhythms. Shift schedules that resulted in circadian rhythms closest to the free-run rhythms were identified as preferred schedules. The numerical results supported Czeisler's findings (1982), indicating the best shift schedules adopt a slow, forward-shifting rotation pattern, rotate shifts after 2-week periods and allow an average of 2 days off per week.


Girdling affects ectomycorrhizal fungal (EMF) diversity and reveals functional differences in EMF community composition in a beech forest.
The relationships between plant carbon resources, soil carbon and nitrogen content, and ectomycorrhizal fungal (EMF) diversity in a monospecific, old-growth beech (Fagus sylvatica) forest were investigated by manipulating carbon flux by girdling. We hypothesized that disruption of the carbon supply would not affect diversity and EMF species numbers if EM fungi can be supplied by plant internal carbohydrate resources or would result in selective disappearance of EMF taxa because of differences in carbon demand of different fungi. Tree carbohydrate status, root demography, EMF colonization, and EMF taxon abundance were measured repeatedly during 1 year after girdling. Girdling did not affect root colonization but decreased EMF species richness of an estimated 79 to 90 taxa to about 40 taxa. Cenococcum geophilum, Lactarius blennius, and Tomentella lapida were dominant, colonizing about 70% of the root tips, and remained unaffected by girdling. Mainly cryptic EMF species disappeared. Therefore, the Shannon-Wiener index (H') decreased but evenness was unaffected. H' was positively correlated with glucose, fructose, and starch concentrations of fine roots and also with the ratio of dissolved organic carbon to dissolved organic nitrogen (DOC/DON), suggesting that both H' and DOC/DON were governed by changes in belowground carbon allocation. Our results suggest that beech maintains numerous rare EMF species by recent photosynthate. These EM fungi may constitute biological insurance for adaptation to changing environmental conditions. The preservation of taxa previously not known to colonize beech may, thus, form an important reservoir for future forest development.


Endomyocardial fibrosis: electron-beam CT features.
To present morphologic and functional electron-beam computed tomographic (CT) features of endomyocardial fibrosis. Twelve patients with histologic evidence of endomyocardial fibrosis and/or definitive echocardiographic and angiocardiographic findings were examined with electron-beam CT. Endomyocardial fibrosis was depicted as linear calcifications and/or a thin tissue band of low attenuation within the endomyocardium. In right ventricular involvement, CT depicted obliteration of the apex associated with extension along the free wall and/or papillary muscles of the tricuspid valve. In left ventricular involvement, a large amount of endocardial tissue led to severe obliteration within the inflow tract and/or of the apex. At ventricular volume analysis, restrictive patterns of the disease were determined. Electron-beam CT allows direct visualization of endomyocardial fibrosis and the resulting volumetric changes and enables distinction of the disease from constrictive pericarditis.


Teaching residents to teach. An instructional program for training pediatric residents to precept third-year medical students in the ambulatory clinic.
To provide second- and third-year pediatric residents with practical teaching skills for precepting third-year medical students in the outpatient clinic. Educational intervention with 3-month follow-up of participants. University teaching hospital. Second- and third-year pediatric residents. A curriculum for a half-day workshop to provide residents with 6 key clinical teaching skills. Residents participated in the workshop and then were observed by trained faculty as they precepted third-year medical students in the pediatric clinic. Direct observation of resident-student precepting encounters, noting the presence or absence of their use of clinical teaching skills taught in the workshop. Twenty-one of 23 pediatric residents participated in the workshop. Observation of 56 resident teaching encounters before and after the workshop showed that the residents improved their clinical teaching skills. Residents valued the workshop, and many suggested it should also be considered for faculty development. Residents can be taught clinical teaching skills in a half-day workshop. These skills also are applicable in various clinical venues. With the increasing interest in using community-based primary care physicians for student and resident education, this curriculum is well suited for training practicing clinicians to teach in their own practice sites.


Nanoscale investigation of the impact of pH and orthophosphate on the corrosion of copper surfaces in water.
Advanced surface characterization techniques were used to systematically investigate either the corrosion or passivation of copper after immersion in water as impacted by pH and orthophosphate water chemistries. Atomic force microscopy, depth profiling with time-of-flight secondary ion mass spectrometry, and X-ray diffraction were used to evaluate changes in surface chemistry of copper surfaces resulting from various chemical treatments. Nanoscale differences in surface morphology are clearly evident after 6 and 24 h immersion in water samples. Orthophosphate and pH dramatically influence the evolution and progression of changes during surface corrosion. For example, in the absence of orthophosphate the surface of copper exposed to water at pH 6 had formed relatively large cubic crystals on the surface up to 400 nm in height. In the presence of orthophosphate, the morphology and growth rate of corrosion byproduct changed dramatically, and the formation of identifiable crystals diminished. These investigations provide insight into the mechanisms of surface passivation and the evolution of nanoscale mineral deposits on surfaces at very early stages of the corrosion of copper surfaces in water.


Effect of acute exercise on mRNA and protein expression of main components of the lipolytic complex in different skeletal muscle types in the rat.
Adipose triglyceride lipase (ATGL) hydrolyses the first bond of triacylglycerols. The activity of the enzyme is elevated by comparative gene identification 58 (CGI-58), and reduced by G0/G1 switch gene 2 (G0S2) protein. There are no data on the effect of acute exercise on the behavior of particular components of the lipolytic complex in different skeletal muscle types, therefore, the aim of the present study was to examine that topic. The experiments were carried out on four groups of male Wistar rats: 1) control 2) rats running on a treadmill at the speed of 18 m/min for 30 min, 3) at the speed of 18 m/min for 120 min, 4) for 30 min at the speed of 28 m/min. We found that each exercise bout induced numerous changes in the expression of mRNA and protein ATGL, hormone-sensitive lipase, CGI-58 and G0S2 in the investigated muscles. These changes, depended to a large extent on a muscle type. In general, the strongest pro-lipolytic response was observed in the soleus, followed by the red section of the gastrocnemius (RG). On the other hand, in the white section of the gastrocnemius protein expression of the components of the lipolytic complex was reduced in response to exercise. These changes were not accompanied by alterations in muscle triacylglycerol content, with the exception of a reduction observed in the RG following 2-hour run. We conclude that a single bout of exercise induces significant effect on the expression of components of the lipolytic complex in skeletal muscle, and that the magnitude of this effect depends on muscle oxidative capacity, as well as the duration and intensity of exercise.


qnr, aac(6')-Ib-cr and qepA genes in Escherichia coli and Klebsiella spp.: genetic environments and plasmid and chromosomal location.
To characterize the location and genetic environments of qnr, aac(6')-Ib-cr and qepA genes related to quinolone resistance in 19 Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca strains. Genetic environments of the indicated genes were studied by cloning, PCR mapping and sequencing. The location of these genes was analysed by S1-PFGE and PFGE-I-CeuI and hybridization with specific probes. Associated antibiotic resistance mechanisms and molecular typing of strains were also investigated. The studied strains carried the aac(6')-Ib-cr, qepA, qnrS1, qnrB6, qnrB4 and oqxAB genes, with aac(6')-Ib-cr being the most prevalent. E. coli strains belonged to sequence types (STs) ST648, ST131, ST224 and ST205, and K. pneumoniae strains to ST433, ST341, ST152, ST15 and ST431. Different genetic environments of quinolone resistance genes were observed, and some of them had not been previously detected and registered in GenBank. The aac(6')-Ib-cr gene was mainly located in class 1 integrons or associated with the Tn1721 transposon in E. coli and associated with the aac(3)-II gene in Klebsiella. All these structures contained mechanisms of gene acquisition and/or dissemination, such as IS26. The studied quinolone resistance genes were mostly detected in IncF and IncN plasmids in E. coli and in IncR plasmids in Klebsiella, but in some strains the chromosomal location of the aac(6')-Ib-cr gene was detected for the first time. The bla(CTX-M-15), bla(OXA-1), tet(A), aac(3)-II and aph(3')-Ia genes and class 1 integrons were found in most strains. The aac(6')-Ib-cr gene was detected for the first time in the chromosome, although a plasmidic location was the most frequently found, with differentiation of plasmids types in E. coli versus Klebsiella.


Parasite dynamics in untreated horses through one calendar year.
Horses are host to a plethora of parasites. Knowledge of the seasonality of parasite egg shedding and transmission is important for constructing parasite control programs. However, studies describing these patterns are sparse, and have largely been conducted only in the United Kingdom. This study evaluated strongylid egg shedding patterns and transmission dynamics of Strongylus vulgaris in naturally infected and untreated mares and foals through one calendar year in Kentucky, USA. The study also investigated the existence of a peri-parturient rise (PPR) in strongylid egg counts in foaling mares and collected information about Strongyloides westeri and Parascaris spp. in the foals. This study was conducted from January to December 2018. A herd of 18 mares, one stallion, and 14 foals born in 2018 were followed throughout the year. Sera and feces were collected biweekly from all horses, and worm burdens enumerated in 13 foals at necropsy. An S. vulgaris ELISA antibody test was run on all serum samples. Fecal egg counts were determined for all horses, and coproculture and qPCR assay were employed to test for the presence of S. vulgaris in the mature horses. Data were analyzed using the proc glimmix procedure in the SAS 9.4 software program. We found a general lack of seasonality in strongylid egg shedding throughout the year among the mature horses, and no PPR was demonstrated. Shedding of S. vulgaris eggs displayed a higher abundance during the spring, but findings were variable and not statistically significant. Anti-S. vulgaris antibody concentrations did not display significant fluctuations in the mature horses, but evidence of passive transfer of antibodies to the foals was demonstrated, and foals assumed their own production of antibodies starting at approximately 20 weeks of age. Overall, colts shed higher numbers of strongylid, ascarid, and S. westeri eggs than fillies. This study demonstrated a lack of seasonality in strongylid egg shedding for the study population, which is in stark contrast to previous studies conducted elsewhere. This strongly suggests that more studies should be done investigating these patterns under different climatic conditions.


A qualitative and semiquantitative SEM study of the morphology of the biofilm on root surfaces of human teeth with endodontic-periodontal lesions.
Over the last decades, scanning electron microscopy (SEM) proved to be invaluable for ultrastructural investigation, allowing imaging of the overall appearance and/or specific features of oral biofilms, e.g., microbial colonies and individual cells, glycocalyx, the presence of inorganic products. The aim of this study was the observation and evaluation of the morphology of the biofilm of endodontic-periodontal lesions (EPL) with a modified protocol involving a simplified histologic sample preparation and a low-vacuum SEM examination method. Twenty-one teeth with endodontic-periodontal involvement, extracted for periodontal reasons, were carefully washed with saline, underwent fixation in modified Karnovsky solution and were dehydrated in alcohol series. Samples were examined under low-vacuum SEM. Radicular surfaces were evaluated qualitatively and semiquantitatively for several characteristics, including the presence of bacterial types, the biofilm morphology and the content of root resorptions. Radicular surfaces were divided in four conventional zones Surfaces were evaluated for several characteristics: Presence of bacterial types, biofilm morphology, presence of root resorptions. High-quality images, relevant for endodontic-periodontal biofilms were collected. Continuous, established biofilm was found on all examined surfaces, its detection varying from 19% of the samples on the wall of cemental cone to 52.3% on the radicular surface of the periodontal pocket. Observed microorganisms included cocci, rods an filaments. Spirils and motile bacteria were only accidentally found. SEM investigation of surfaces involved in EPL revealed less surfaces covered by mature biofilm (in only 28.5% of the samples in the 'transition zone'), especially rods and filaments associated with cemental resorptions and calculus. Biofilm elements were better represented in periodontal pockets than in other zones of EPL (detected in up to 81% of the samples). A strong correlation between mature biofilm and the presence of cocci appears on all investigated zones (P<0.01). Microbiota appeared to be morphologically similar in apical and periodontal areas, especially in old EPL.


Aqueous Humor Biomarkers of Retinal Glial Cell Activation in Patients With or Without Age-Related Cataracts and With Different Stages of Diabetic Retinopathy.
To clarify the expression of biomarkers of retinal glial cell activation in the aqueous humor (AH) of patients with and without age-related cataracts (ARCs) at different stages of diabetic retinopathy (DR). Patients were stratified by the presence of ARCs and then grouped by the presence of diabetes mellitus (DM), nonproliferative DR (NPDR), proliferative DR (PDR), and controls. Water channel aquaporin 1 (AQP1), water channel aquaporin 4 (AQP4), inwardly rectifying potassium channel 4.1 (Kir4.1), and glial fibrillary acidic protein (GFAP) were assayed in AH samples by ELISAs. We enrolled 82 patients. The AQP1 concentration was higher in AH from cataract control patients than in control patients without cataracts (P < 0.05). The APQ1 concentration was also higher in patients with DM, NPDR, and PDR than in controls (P < 0.05). The concentrations of AQP4 and GFAP were significantly increased in patients with NPDR and PDR (P < 0.05) but not in patients with DM. Kir4.1 concentration was significantly decreased in patients with NPDR and PDR (P < 0.05), but the decrease in patients with DM did not reach significance. There were no differences in AQP4, Kir4.1, and GFAP between patients with and without ARCs. Increased AQP1 in AH may be a biomarker for ARCs in patients without diabetes and a biomarker for retinal glial cell activation in patients with diabetes without cataracts. AQP4, Kir4.1, and GFAP levels in AH suggested that retinal glial cell activation was affected by the progression of DR.


Effect of low temperature and calcium on survival and membrane properties of isolated winter wheat cells.
Isolated cells obtained by enzymic digestion of young primary leaves of cold-hardened, dark-grown Kharkov winter wheat (Triticum aestivum L.) were exposed to various low temperature stresses. The initial uptake of (86)Rb was generally decreased by increasing concentrations of Ca(2+), but after longer periods of incubation, the inhibiting effect of high Ca(2+) levels diminished. Viability of isolated cells suspended in water declined rapidly when ice encased at -1 degrees C, while in the presence of 10 millimolar Ca(2+) viability declined only gradually over a 5-week period. Ice encasement markedly reduced (86)Rb uptake prior to a significant decline in cell viability or increased ion efflux. Cell damage increased progressively when the icing temperature was reduced from -1 to -2 and -3 degrees C, but the presence of Ca(2+) in the suspending medium reduced injury. Cell viability and ion uptake were reduced to a greater extent following slow cooling than after rapid cooling to subfreezing temperatures ranging from -10 to -30 degrees C. The results from this study support the view that an early change in cellular properties due to prolonged ice encasement at -1 degrees C involves the ion transport system, whereas cooling to lower subfreezing temperatures for only a few hours results in more general membrane damage, including loss of semipermeability of the plasma membrane.


The influence of maternal psychological distress on the mode of birth and duration of labor: findings from the FinnBrain Birth Cohort Study.
Antepartum depression, general anxiety symptoms, and pregnancy-related anxiety have been recognized to affect pregnancy outcomes. Systematic reviews on these associations lack consistent findings, which is why further research is required. We examined the associations between psychological distress, mode of birth, epidural analgesia, and duration of labor. Data from 3619 women with singleton pregnancies, from the population-based FinnBrain Birth Cohort Study were analyzed. Maternal psychological distress was measured during pregnancy at 24 and 34 weeks, using the Pregnancy-Related Anxiety Questionnaire-Revised 2 (PRAQ-R2) and its subscale "Fear of Giving Birth" (FOC), the anxiety subscale of the Symptom Checklist-90 (SCL-90) and the Edinburgh Postnatal Depression Scale (EPDS). Mode of birth, epidural analgesia, and labor duration were obtained from the Finnish Medical Birth Register. Maternal psychological distress, when captured with PRAQ-R2, FOC, and SCL-90, increased the likelihood of women having an elective cesarean section (OR: 1.04, 95% CI 1.01-1.06, p = .003; OR: 1.13, 95% CI 1.07-1.20, p < .001; OR: 1.06, 95% CI 1.03-1.10, p = .001), but no association was detected for instrumental delivery or emergency cesarean section. A rise in both the PRAQ-R2, and FOC measurements increased the likelihood of an epidural analgesia (OR: 1.02, 95% CI 1.01-1.03, p = .003; OR: 1.09, 95% CI 1.05-1.12, p < .001) and predicted longer second stage of labor (OR: 1.01, 95% CI 1.00-1.01, p = .023; OR: 1.03, 95% CI 1.02-1.05, p < .001). EPDS did not predict any of the analyzed outcomes. The results indicate that maternal anxiety symptoms (measured using PRAQ-R2, FOC, and SCL-90) are associated with elective cesarean section. Psychological distress increases the use of epidural analgesia, but is not associated with complicated vaginal birth.


Somatostatin receptor: scintigraphy and radionuclide therapy.
Peptide receptor scintigraphy is more sensitive at the biological than anatomical level, in contrast to conventional imaging, which it complements. Neuroendocrine tumours have the most somatostatin receptors in vitro and their metastases are somatostatin receptor positive in vitro, so that [111In-DTPA-D-Phe1]octreotide (OCT) can be used to image them. OCT was compared with conventional imaging techniques (CON) in a European Multicentre Trial. In 350 evaluable patients, CON detected 88%, and OCT 80% (glucagonomas 100%, VIPomas 88%, carcinoids 87%, non-functioning islet cell tumours 82%, insulinomas 46%) of tumour sites but there was no systematic use of abdominal single-photon-emission computerised tomography. OCT demonstrated multiple tumour sites in 62 of 178 patients in whom CON had found only 1 lesion, with 60% confirmed. 12/16 lesions detected by OCT in 11 patients with no lesions according to CON were also confirmed. The impact of OCT on management was evaluated in 235 patients and affected 40%: it determined 29 surgical decisions, led to octreotide therapy in 47, and modified octreotide dose in 18. Six end-stage patients with neuroendocrine tumours were treated with OCT radionuclide therapy (up to a cumulative dose of 53 GBq per patient) in a phase I trial. There were no major side-effects after up to 2 years treatment, with impressive effects on hormone production and a likely anti-proliferative effect.


Severe impairment of leukocyte rolling in venules of core 2 glucosaminyltransferase-deficient mice.
Leukocyte capture and rolling are mediated by selectins expressed on leukocytes (L-selectin) and the vascular endothelium (P- and E-selectin). To investigate the role of core 2 beta1-6-N-glucosaminyltransferase (C2GlcNAcT-I) for synthesis of functional selectin ligands in vivo, leukocyte rolling flux and velocity were studied in venules of untreated and tumor necrosis factor-alpha (TNFalpha)-pretreated autoperfused cremaster muscles of C2GlcNAcT-I-deficient (core 2(-/-)) and littermate control mice. In untreated core 2(-/-) mice, leukocyte rolling was dramatically reduced with markedly increased rolling velocities (81 +/- 4 microm/s vs 44 +/- 3 microm/s). The reduced rolling in core 2(-/-) mice was due mainly to severely impaired binding of P-selectin to P-selectin glycoprotein ligand-1 (PSGL-1). Some rolling remained after blocking PSGL-1 in controls but not in core 2(-/-) mice. In TNFalpha-pretreated mice, rolling was markedly reduced in core 2(-/-) mice owing to impaired P-selectin- and E-selectin-mediated rolling. Rolling velocities in core 2(-/-) mice treated with an E-selectin-blocking monoclonal antibody (59 +/- 4 microm/s) were significantly higher than in controls (14 +/- 1 microm/s), which provides further evidence for the severe impairment in P-selectin-mediated rolling. In conclusion, P-selectin ligands including PSGL-1 are largely C2GlcNAcT-I dependent. In addition, E-selectin-mediated rolling in vivo is partially dependent on the targeted C2GlcNAcT-I. (Blood. 2001;97:3812-3819)


Expanded and updated data and a query pipeline for iBeetle-Base.
The iBeetle-Base provides access to sequence and phenotype information for genes of the beetle Tribolium castaneum. It has been updated including more and updated data and new functions. RNAi phenotypes are now available for >50% of the genes, which represents an expansion of 60% compared to the previous version. Gene sequence information has been updated based on the new official gene set OGS3 and covers all genes. Interoperability with FlyBase has been enhanced: First, gene information pages of homologous genes are interlinked between both databases. Second, some steps of a new query pipeline allow transforming gene lists from either species into lists with related gene IDs, names or GO terms. This facilitates the comparative analysis of gene functions between fly and beetle. The backend of the pipeline is implemented as endpoints of a RESTful interface, such that it can be reused by other projects or tools. A novel online interface allows the community to propose GO terms for their gene of interest expanding the range of animals where GO terms are defined. iBeetle-Base is available at http://ibeetle-base.uni-goettingen.de/.


Association of malignant lymphoma with pancreatic adenocarcinoma: a clinicopathologic study of three patients.
Three patients with pancreatic adenocarcinoma are studied who had a prior history of malignant lymphoma. No common predisposing factors for the development of pancreatic adenocarcinoma were identified. We conclude that patients with malignant lymphoma who have new or persistent pancreatic masses must be evaluated for the possibility of a second primary neoplasm.


Bone Marrow Aspirate Concentrate versus Platelet Rich Plasma or Hyaluronic Acid for the Treatment of Knee Osteoarthritis.
Background: In the last decade, regenerative therapies have become one of the leading disease modifying options for treatment of knee osteoarthritis (OA). Still, there is a lack of trials with a direct comparison of different biological treatments. Our aim was to directly compare clinical outcomes of knee injections of Bone Marrow Aspirate Concentrate (BMAC), Platelet-rich Plasma (PRP), or Hyaluronic acid (HA) in the OA treatment. Methods: Patients with knee pain and osteoarthritis KL grade II to IV were randomized to receive a BMAC, PRP, and HA injection in the knee. VAS, WOMAC, KOOS, and IKDC scores were used to establish baseline values at 1, 3, 6, 9, and 12 months. All side effects were reported. Results: A total of 175 patients with a knee osteoarthritis KL grade II-IV were randomized; 111 were treated with BMAC injection, 30 with HA injection, and 34 patients with PRP injection. There were no differences between these groups when considering KL grade, BMI, age, or gender. There were no serious side effects. The mean VAS scores after 3, 7, 14, and 21 days showed significant differences between groups with a drop of VAS in all groups but with a difference in the BMAC group in comparison to other groups (p < 0.001). There were high statistically significant differences between baseline scores and those after 12 months (p < 0.001) in WOMAC, KOOS, KOOS pain, and IKDC scores, and in addition, there were differences between these scores in the BMAC group in comparison with other groups, except for the PRP group in WOMAC and the partial IKDC score. There were no differences between the HA and PRP groups, although PRP showed a higher level of clinical improvement. Conclusions: Bone marrow aspirate concentrate, Leukocyte rich Platelet Rich Plasma, and Hyaluronic acid injections are safe therapeutic options for knee OA and provide positive clinical outcomes after 12 months in comparison with findings preceding the intervention. BMAC could be better in terms of clinical improvements in the treatment of knee OA than PRP and HA up to 12 months. PRP provides better outcomes than HA during the observation period, but these results are not statistically significant. More randomized controlled trials and high quality comparative studies are needed for direct correlative conclusions.


Susceptibility trends of ceftolozane/tazobactam and comparators when tested against U.S. gram-negative bacterial surveillance isolates (2012-2018).
Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. Ceftolozane/tazobactam has been approved in >60 countries for treating complicated urinary tract infections, acute pyelonephritis, complicated intra-abdominal infections (with metronidazole), and hospital-acquired pneumonia, including ventilator-associated pneumonia in adults. We analyzed susceptibilities for 35,882 gram-negative isolates collected from patients in 35 US medical centers from 2012 to 2018. The rate of multi-drug resistant Enterobacterales was stable (9.5%-10.1%), while the P. aeruginosa multi-drug resistance rate increased from 15.5% in 2012 to 22.9% in 2018. The carbapenem-resistant Enterobacterales rates varied from 0.9% to 2.2% and extended-spectrum β-lactamase phenotypes increased from 10.5% to 16.8%. The most active drugs against P. aeruginosa were ceftolozane/tazobactam (95.8%-97.5% susceptible) and amikacin (93.9%-98.0%); against Enterobacterales, amikacin (97.9%-98.8%), meropenem (97.7%-98.8%), and ceftolozane/tazobactam (93.3%-95.6%) were the most active. These data suggest that ceftolozane/tazobactam has effective in vitro activity against organisms causing serious gram-negative infections.


The role of age, environmental and occupational factors on semen density.
The problem of effect of the environment on human reproduction has been in the focus of researchers' interest for many years. To examine the relationship between semen density in males with reproduction problems, and their age, living and working conditions. The study covered 224 males with reproduction problems. The study had a prospective character and was conducted in three stages - the first stage was carried out using the questionnaire devised by the authors; the second and the third stages consisted in the examination and evaluation of male semen density. Statistical analysis was used to search for the relationship between these groups and variables adopted in the study, i.e. age, occupation performed, place of residence, self-reported housing conditions and material standard, reporting by the males in the study of arduousness of work or health hazards perceived by the males examined, and duration of employment in such conditions. The males in the study were divided into three groups according to their semen density. Group I (20 × 10(6) mln/ml or more) included 62 (27.7%) respondents, Group II (below 20 × 10(6) mln/ml) covered 121 males (54.0%), while Group III (only single spermatozoa or none) - 41 males (18.3%). Male semen density are significantly correlated with men's ages and jobs as well as the general evaluations of the jobs held by the men (p<0.05). No significant relationship is observed between living conditions, arduous work conditions and occupational hazards as perceived by males, or duration of employment in such conditions, and male semen density (p>0.05). The results obtained encourage continuation of the studies and cover a larger group of males with reproduction problems.


Doppler Evaluation of Carotid Vessels in Type 2 Diabetes.
Type 2 diabetes considered as a compound of metabolic syndrome. It can cause both micro and macrovascular complications. Diabetes is a strong risk factor in the development of atherosclerosis and likewise carotid artery disease. Carotid artery stenosis may cause stroke. Doppler ultrasound is the most common imaging technique for the diagnosis of carotid disease. Objective of the study was to assess the percentage of atherosclerotic carotid disease in asymptomatic Type 2 diabetics (T2D) by Doppler sonography and to find out the association of different risk factors of diabetic patient with atherosclerosis. A cross sectional study was done. A total of 43 type 2 diabetic patients (27 male, 16 female) referred from the out patient department and admitted patients in Mymensingh Medical College Hospital (MMCH) during January 2017 to December 2017 for the purpose of evaluation of intima media thickness (IMT) and carotid artery stenosis by Duplex color Doppler ultrasonography examination were enrolled in this study. Patients with previous history of recent stroke or transient ischemic attack (<6 weeks), history of carotid surgery or cervical radiotherapy were excluded. Carotid artery disease was found 65.1% in asymptomatic type 2 diabetics. Among them increased IMT in 48.8% and carotid stenosis was present in 37.2% and >50% stenosis (Peak systolic velocity >125cm/sec) was present in 9.3%. Age >50% years, smoking, duration of DM >10 years, hypertension, history of ischaemic heart disease and history of diabetic retinopathy were found to be associated with carotid atherosclerosis as well as carotid stenosis. High percentage of carotid artery disease (65.1%) was found in asymptomatic type 2 diabetes mellitus. This result suggests the need for carotid Doppler evaluation of all Type 2 diabetics as a first measure of stroke prevention, with the hope that timely intervention might avert stroke and its accompanying disability.


CXC family of chemokines as prognostic or predictive biomarkers and possible drug targets in colorectal cancer.
Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women, worldwide. In the early stages of the disease, biomarkers predicting early relapse would improve survival rates. In metastatic patients, the use of predictive biomarkers could potentially result in more personalized treatments and better outcomes. The CXC family of chemokines (CXCL1 to 17) are small (8 to 10 kDa) secreted proteins that attract neutrophils and lymphocytes. These chemokines signal through chemokine receptors (CXCR) 1 to 8. Several studies have reported that these chemokines and receptors have a role in either the promotion or inhibition of cancer, depending on their capacity to suppress or stimulate the action of the immune system, respectively. In general terms, activation of the CXCR1/CXCR2 pathway or the CXCR4/CXCR7 pathway is associated with tumor aggressiveness and poor prognosis; therefore, the specific inhibition of these receptors is a possible therapeutic strategy. On the other hand, the lesser known CXCR3 and CXCR5 axes are generally considered to be tumor suppressor signaling pathways, and their stimulation has been suggested as a way to fight cancer. These pathways have been studied in tumor tissues (using immunohistochemistry or measuring mRNA levels) or serum [using enzyme-linked immuno sorbent assay (ELISA) or multiplexing techniques], among other sample types. Common variants in genes encoding for the CXC chemokines have also been investigated as possible biomarkers of the disease. This review summarizes the most recent findings on the role of CXC chemokines and their receptors in CRC and discusses their possible value as prognostic or predictive biomarkers as well as the possibility of targeting them as a therapeutic strategy.


Role of calcium-channel blockers in preventing acute and chronic renal injury.
Calcium-channel blockers (CCBs) have been shown to afford protection against acute (ARF) and chronic renal failure (CRF). The effects of CCBs against acute renal injury occur at both the vascular and tubular epithelial level. At the vascular level, experimental ARF-associated loss of renal autoregulation and hypersensitivity to renal nerve stimulation has been shown to be reversed by CCBs. These beneficial vascular effects of CCBs occur on the background of the finding that renal ischemic injury is associated with an increase in cellular Ca2+ concentration. A rise in tubular epithelial Ca2+ concentration also occurs very early after a renal ischemic insult. This effect of ischemia is associated with evidence of membrane depolarization, opening of slow calcium channels, increased cellular Ca2+ uptake, and reversal by CCBs. There is evidence that the increased cellular Ca2+ uptake activates phospholipases, which prolong and increase membrane damage. Experimental CRF is also associated with increased renal cellular Ca2+ concentration, an effect that can be attenuated by CCBs. The CCBs probably slow progression of CRF by both cytoprotective and antihypertensive effects. These findings of vascular and tubular effects of CCBs in experimental ARF and CRF have led to their clinical use to prevent initial dysfunction of cadaveric kidney transplants, cyclosporine nephrotoxicity, radiocontrast-induced ARF, and progression of CRF. Randomized clinical studies are necessary to further examine the efficacy of CCBs in ARF and CRF.


Effects of curcumin on artery blood gas index of rats with pulmonary fibrosis caused by paraquat poisoning and the expression of Smad 4, Smurf 2, interleukin-4 and interferon-γ.
Effects of curcumin on artery blood gas index of rats with pulmonary fibrosis caused by paraquat poisoning and the expression of Mothers against decapentaplegic homolog 4 (Smad4), Smad ubiquitination regulatory factor 2 (Smurf2), interleukin-4 (IL-4) and interferon-γ (IFN-γ) were explored. A total of 54 Wistar rats were randomly selected, of which 36 rats were selected for paraquat poisoning pulmonary fibrosis modeling, and 18 were used in the control group for normal feeding. Then, 18 rats were randomly selected from the modeled groups and injected with curcumin and classified as the curcumin group. The remaining 18 rats were not processed and 17 were successfully modeled as the paraquat group. The expression of SMAD4, Smurf2, IL-4 and INF-γ was detected by enzyme-linked immunosorbent assay. Abdominal aortic blood was taken for determination of pH, arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2). The artery blood PaO2 and serum INF-γ of the curcumin and paraquat groups were significantly higher on day 1 than those on day 5 (P<0.05). The artery blood PaO2 and serum INF-γ in the curcumin group were higher than those in the paraquat group (P<0.05). The artery blood PaCO2, serum Smad4, Smurf2 and IL-4 in the curcumin group were significantly lower on day 1 than those on day 5 (P<0.05). The artery blood PaCO2, serum Smad4, Smurf2 and IL-4 in the paraquat group were significantly lower on day 1 than those on day 5 (P<0.05). The PaCO2, serum Smad4, Smurf2 and IL-4 in the curcumin group were lower than those in the paraquat group (P<0.05). In conclusion, curcumin can effectively improve pulmonary fibrosis in rats after treatment with paraquat poisoning. The results show that it is expected to be an effective drug for the treatment of paraquat, and provide effective reference and guidance for clinical treatment.


Personalized Radioproteomics: Identification of a Protein Biomarker Signature for Preemptive Rescue by Tocopherol Succinate in CD34+ Irradiated Progenitor Cells Isolated from a Healthy Control Donor.
Tocopherol succinate (TS) has been shown to protect mice against acute radiation syndrome, however, its exact mechanism of action and its possible use in humans has not yet been evaluated. Our approach has been to test the radioprotectant properties of TS on CD34-positive stem cells from healthy volunteers. We hypothesize that a radioproteomics strategy can identify a drug-dependent, personalized proteomics signature for radioprotection. To directly test the radioproteomics hypothesis, we treated human CD34-positive stem cells with 20 μM TS for 24 h, and then exposed the cells to 2 Gy of cobalt-60 gamma-radiation. We isolated protein from all cultures and used a high throughput Antibody Microarray (AbMA) platform to measure concentrations of 725 low abundance proteins. As an in vivo control, we also tested mouse CD34-positive stem cells using the same preemptive TS paradigm on progenitor colony forming units. TS pretreatment of in vitro or in vivo CD34-positive stem cells rescued radiation-induced loss of colony-forming potential of progenitors. We identified 50 of 725 proteins that could be preemptively rescued from radiation-induced reduction by pretreatment with TS. Ingenuity Pathway Analysis (IPA) reveals that the modified proteins fall into categories dominated by epigenetic regulation, DNA repair, and inflammation. Our results suggest that radioproteomics can be used to develop personalized medicine for radioprotection using protein signatures from primary CD34-positive progenitors derived from the patient or victim prior to radiation exposure. The protective effect of TS may be due to its ability to preemptively activate epigenetic mechanisms relevant to radioprotection and to preemptively activate the programs for DNA repair and inflammation leading to cell survival.


Linking Spinal Cord Injury Data Sets to Describe the Patient Journey Following Injury: A Protocol.
To optimize traumatic spinal cord injury (tSCI) care, administrative and clinical linked data are required to describe the patient's journey. To describe the methods and progress to deterministically link SCI data from multiple databases across the SCI continuum in British Columbia (BC) and Ontario (ON) to answer epidemiological and health service research questions. Patients with tSCI will be identified from the administrative Hospital Discharge Abstract Database using International Classification of Diseases (ICD) codes from Population Data BC and ICES data repositories in BC and ON, respectively. Admissions for tSCI will range between 1995-2017 for BC and 2009-2017 for ON. Linkage will occur with multiple administrative data holdings from Population Data BC and ICES to create the "Admin SCI Cohorts." Clinical data from the Rick Hansen SCI Registry (and VerteBase in BC) will be transferred to Population Data BC and ICES. Linkage of the clinical data with the incident cases and administrative data at Population Data BC and ICES will create subsets of patients referred to as the "Clinical SCI Cohorts" for BC and ON. Deidentified patient-level linked data sets will be uploaded to a secure research environment for analysis. Data validation will include several steps, and data analysis plans will be created for each research question. The creation of provincially linked tSCI data sets is unique; both clinical and administrative data are included to inform the optimization of care across the SCI continuum. Methods and lessons learned will inform future data-linking projects and care initiatives.


Two-step paretial least square regression classifiers in brain-state decoding using functional magnetic resonance imaging.
Multivariate analysis methods have been widely applied to decode brain states from functional magnetic resonance imaging (fMRI) data. Among various multivariate analysis methods, partial least squares regression (PLSR) is often used to select relevant features for decoding brain states. However, PLSR is seldom directly used as a classifier to decode brain states from fMRI data. It is unclear how PLSR classifiers perform in brain-state decoding using fMRI. In this study, we propose two types of two-step PLSR classifiers that use PLSR/sparse PLSR (SPLSR) to select features and PLSR for classification to improve the performance of the PLSR classifier. The results of simulated and real fMRI data demonstrated that the PLSR classifier using PLSR/SPLSR to select features outperformed both the PLSR classifier using a general linear model (GLM) and the support vector machine (SVM) using PLSR/SPLSR/GLM in most cases. Moreover, PLSR using SPLSR to select features showed the best performance among all of the methods. Compared to GLM, PLSR is more sensitive in selecting the voxels that are specific to each task. The results suggest that the performance of the PLSR classifier can be largely improved when the PLSR classifier is combined with the feature selection methods of SPLSR and PLSR.


Current rodent models for the study of empathic processes.
Empathy is a complex phenomenon critical for group survival and societal bonds. In addition, there is mounting evidence demonstrating empathic behaviors are dysregulated in a multitude of psychiatric disorders ranging from autism spectrum disorder, substance use disorders, and personality disorders. Therefore, understanding the underlying drive and neurobiology of empathy is paramount for improving the treatment outcomes and quality of life for individuals suffering from these psychiatric disorders. While there is a growing list of human studies, there is still much about empathy to understand, likely due to both its complexity and the inherent limitations of imaging modalities. It is therefore imperative to develop, validate, and utilize rodent models of empathic behaviors as translational tools to explore this complex topic in ways human research cannot. This review outlines some of the more prevailing theories of empathy, lists some of the psychiatric disorders with disrupted empathic processes, describes rat and mouse models of empathic behaviors currently used, and discusses ways in which these models have elucidated social, environmental, and neurobiological factors that may modulate empathy. The research tools afforded to rodent models will provide an increasingly clear translational understanding of empathic processes and consequently result in improvements in care for those diagnosed with any one of the many psychiatric disorders.


Amyloidosis in saphenous vein aortocoronary bypass grafts.
A patient in whom idiopathic amyloidosis of aortocoronary saphenous vein grafts was found at autopsy two years after myocardial revascularization due to coronary atherosclerosis is reported. Idiopathic generalized immunocyte derived amyloidosis extensively studied at autopsy was obviously present at the time of surgery although it remained unnoticed macroscopically in the inserted graft. It appears that simultaneously with arterialization further deposition and also significant redistribution of amyloid within the walls of the vein grafts additionally took place after their insertion. It seems interesting that in spite of the amyloidosis the grafts functioned well and were found patent two years after surgery.


Genetic deletions of glutathione-S-transferase as a risk factor in squamous cell carcinoma of the larynx: a preliminary report.
To test whether genetic deletions of glutathione-S-transferase (GST) are associated with squamous cell carcinoma (SCC) of the larynx. GST are a group of detoxifying enzymes that may help reduce the risk of developing cancer in response to environmental carcinogens. Polycyclic aromatic hydrocarbons, found in high concentration in cigarette smoke, are known carcinogens especially for SCC of the larynx. Individuals with absolute or relative deficiency of the GST enzyme system may therefore be at a higher risk of developing laryngeal carcinoma. Genotyping for GST-M1 and GST-T1 was performed using polymerase chain reaction (PCR) assay on fresh frozen tissue specimens of 20 patients with SCC of the larynx and on 20 control subjects with a similar smoking history. Because this assay results in the absence of a PCR product in individuals expressing the GST-M1/GST-T1 null genotype, oligonucleotide primers that amplify a portion of the albumin gene were included in a multiplex PCR as a positive control for DNA quality and PCR conditions. The chi-square test was used for statistical analysis. GST-M1 gene was deleted in 80% of patients with laryngeal SCC and in 50% of control subjects (P <.05). No statistically significant difference was observed in the incidence of GST-T1 gene deletion in patients with SCC of the larynx and control subjects. GST-M1 gene deletion was significantly associated with SCC of the larynx and may produce a risk for this particular disease.


The patterns of Cd-binding proteins in rice and wheat seed and their stability.
The protein-binding forms of cadmium in polluted rice and wheat seeds and their stability were investigated using the methods of Sephadex chromatography. Three absorption peaks (F-I, F-II and F-III) were identified in Tris-HCl extraction of rice and wheat on Sephadex G 75. The Cd in the protein extracts from rice and wheat seeds was distributed mainly in the fractions of F-I and F-III. The apparent molecular weights of Cd-binding proteins for F-I and F-III were 54.5 and 5.5 KD, respectively. The components of amino acid for the protein bound with heavy metals were different. There were high contents of glutamic acid, cysteine, valine, isoleucine, leucine and tyrosine in the protein extracts of rice and wheat. After cooking, the Cd-binding proteins were destroyed. High molecular weight protein-binding form (54.5 KD) was broken into low molecular weight complex (5.5 KD) or tiny peptide chain. Simultaneously, Cd bound with protein was released, or mainly bound with protein of smaller molecular size. Enzyme treatment (pepsin and trypsin) also caused a destruction of Cd binding protein and a change in the distribution of Cd in the eluent. The concentrations of Cd in the elution of first and third peak decreased markedly, and the Cd distribution was observed in the elution after third peak (F-III).


CFD simulation of pollutant dispersion around isolated buildings: on the role of convective and turbulent mass fluxes in the prediction accuracy.
Computational Fluid Dynamics (CFD) is increasingly used to predict wind flow and pollutant dispersion around buildings. The two most frequently used approaches are solving the Reynolds-averaged Navier-Stokes (RANS) equations and Large-Eddy Simulation (LES). In the present study, we compare the convective and turbulent mass fluxes predicted by these two approaches for two configurations of isolated buildings with distinctive features. We use this analysis to clarify the role of these two components of mass transport on the prediction accuracy of RANS and LES in terms of mean concentration. It is shown that the proper simulation of the convective fluxes is essential to predict an accurate concentration field. In addition, appropriate parameterization of the turbulent fluxes is needed with RANS models, while only the subgrid-scale effects are modeled with LES. Therefore, when the source is located outside of recirculation regions (case 1), both RANS and LES can provide accurate results. When the influence of the building is higher (case 2), RANS models predict erroneous convective fluxes and are largely outperformed by LES in terms of prediction accuracy of mean concentration. These conclusions suggest that the choice of the appropriate turbulence model depends on the configuration of the dispersion problem under study. It is also shown that for both cases LES predicts a counter-gradient mechanism of the streamwise turbulent mass transport, which is not reproduced by the gradient-diffusion hypothesis that is generally used with RANS models.


[Species dynamic change of added Rare Earth element in soil].
After Rare Earth elements (REEs) was applied into soil, content of exchangeable species decreased obviously with time lapsing. The fastest decrease of content of exchangeable species occurred at wheat tillering stage. A part of the lost content of exchangeable species was absorbed by wheat, and the other part of that was absorbed by soil. The surface activity of iron/manganese oxide was influenced obviously by the secretion function of root, content of iron/manganese oxide binding species rapidly increased before wheat jointing stage, but it decreased quickly after wheat jointing stage. At all time, content of carbonate binding species decreased with time lapsing, and content of residual species and content of organic binding species didn't change.


Elderly women have blunted response to resistance training despite reduced antagonist coactivation.
To test the ability of a combination high-velocity/high-resistance training program to enhance knee extensor muscle strength, power, nervous activation of muscle, and muscle activation time in inactive women and compare the response to training between young and old women. The study involved 49 inactive women, with young (18-33 yr, n = 25) and old (65-84 yr, n = 24) distributed to training and control groups using blocked randomization. Electrically evoked muscle twitches were measured for the knee extensors; then maximal, voluntary, isometric knee extensions were performed in a visually cued reaction time (RT) task, followed by 8 wk of explosive resistance training. Training increased peak torque (+12%, P = 0.03) and reduced antagonist coactivation (-13%, P = 0.02) similarly for both age groups. Young training group increased the rate of torque development by 34% compared to young controls (-7%), old training (+9%), and old controls (+8%) (P = 0.002). Young training group increased impulse by 53%, which was greater than young controls (-11%), old training (+12%), and old controls (+9%) (P = 0.001). Resistance training did not change electrically evoked twitch, RT (premotor time, motor time, or reaction time), or nervous activation measures (onset EMG amplitude or rate of EMG rise). Explosive force training was ineffective at enhancing muscle twitch characteristics, neural drive, or RT in young or old women. It did enhance peak muscle force in both young and old, modulated through a reduction in antagonist coactivation. Older participants showed less of an improvement in the rate of torque development and contractile impulse than young, indicating either that this sample of older women had a reduced capacity to develop muscle power or that the 8-wk isokinetic resistance training program used in this study was not a sufficient stimulus for adaptation.