A Rational and Standardized Prenatal Examination.
As prenatal care is in transition after the COVID-19 pandemic, reviewing fundamental physical examination approaches is necessary for providers examining obstetrical patients. The objective of this review is 3-fold: (1) convey why the age of telemedicine necessitates reconsideration of the standardized physical examination in routine prenatal care; (2) identify the screening efficacy of examination maneuvers used within a standard prenatal examination of the neck, heart, lungs, abdomen, breasts, skin, lower extremities, pelvis, and fetal growth; and (3) propose an evidence-based prenatal physical examination. A comprehensive literature review identified relevant research, review articles, textbook chapters, databases, and societal guidelines. We conclude that an evidence-based prenatal examination for asymptomatic patients includes the following maneuvers: inspection and palpation for thyromegaly and cervical lymphadenopathy, cardiac auscultation, fundal height measurement, and a pelvic examination for purposes including testing for gonorrhea and chlamydia, assessing pelvimetry, and assessing cervical dilation later in the pregnancy, intrapartum, or in the setting of ultrasonogram-detected prelabor preterm cervical shortening. Although not true of all physical examination maneuvers, this article demonstrates that there are maneuvers that continue to play important screening roles in asymptomatic patients. With the increase in virtual visits and fewer in-person prenatal appointments, the rational basis for maneuvers recommended in this review should inform decision making around the prenatal examination performed.


Long-term outcomes of surgically removed migrated polyalkylimide (bio-alcamid) filler to the periorbital area.
To report the long-term follow-up results after surgical excision of migrated Bio-Alcamid fillers to the Periorbita area. A retrospective case series of all patients who underwent surgical removal of migrated Bio-Alcamid fillers to the Periorbita area with minimal follow-up of 1 year from January 2009 to January 2018 was done. 16 female patients (24-52 y) presented with an upper or lower eyelid swelling 3-7 years following a filler injection in the nasal bridge, temporal or malar area. All patients had surgical excision of a granulomatous mass ranging in size from 1-3.5 cm. The histopathology report revealed a giant cell reaction in all patients. Follow-up periods ranged from 1 to 8 years. One patient developed lid retraction and another had recurrence 3 years later; the remaining had an unremarkable course. Filler migration is one of the potential complications associated with Bio-Alcamid soft tissue injection. It is important for all physicians to assess nodules/masses/swelling in the facial area to be aware that soft tissue fillers may migrate to a location away from their intended site of injection years after the injection. Patients undergoing surgical excision tend to have favorable overall long-term outcomes in terms of aesthetics and incidence of recurrence.


Applications of Resting-State Functional Connectivity to Neurodegenerative Disease.
Neurodegenerative diseases target specific large-scale neuronal networks, leading to distinct behavioral and cognitive dysfunctions. Resting-state functional magnetic resonance imaging (rsfMR imaging)-based functional connectivity method maps symptoms-associated functional network deterioration in vivo. This article summarizes accumulating functional connectivity findings supporting the network-based neurodegeneration hypothesis. Understanding of disease mechanism can further guide early detection and predictions of disease progression and inform development of more effective treatment. With better clinical phenotyping and larger samples across multiple sites, we discuss several possible future directions to further develop rsfMR imaging-based functional connectivity methods into scientifically and clinically useful assays for neurodegenerative disorders.


Metastatic patterns in squamous cell cancer of the head and neck.
This retrospective study on 832 head and neck cancer patients who died between 1961 and 1985 was carried out to determine the incidence and sites of distant metastases. All patients were staged prior to definitive treatment and were autopsied. The overall incidence of distant metastases was 47 percent. The hypopharynx had the highest incidence of distant metastases (60 percent), followed by the base of the tongue (53 percent) and the anterior tongue (50 percent). Of the 387 patients with distant metastases, 91 percent died with uncontrolled tumor either at the primary site or in the neck. The lung was the most common site of distant metastases (80 percent), followed by the mediastinal nodes (34 percent), the liver (31 percent), and bone (31 percent). Overall, 6 percent of the patients had stage I disease, 20 percent had stage II disease, 32 percent had stage III disease, and 43 percent had stage IV disease. The highest incidence of distant metastases was found in those patients with stage IV disease (193 of 350 patients, 55 percent). We believe that the initial stage of disease does appear to be related to the ultimate development of the distant metastases.


Anticancer drug pharmacodynamics.
A considerable amount of information is available on the pharmacokinetics of anticancer drugs, but much less is known of their pharmacodynamics, that is of the relationship between therapeutic or toxic response and drug concentration. Drug dosage regimens which are to achieve defined therapeutic objectives can only be designed when both the pharmacokinetic and the pharmacodynamic characteristics of a drug are known. There are a few reports in the literature of relationships in man between toxic response and pharmacokinetic parameters of anticancer drugs, and an even smaller number of reports of relationships between therapeutic response and pharmacokinetic parameters. It is suggested that the lack of pharmacodynamic information is currently limiting the application of pharmacokinetic information to cancer therapy. Ways of improving knowledge of the pharmacodynamics of anticancer drugs are suggested.


Carcinoma ex papillary cystadenoma lymphomatosum. Malignant Warthin's tumor.
Epithelial malignancy in a Warthin's tumor exists in three forms. The most common is a coexistent, separate neoplasm. Metastasis to the lymphoid component of Warthin's tumor follows, and the least common is a primary carcinoma arising from the ductal component of the tumor.


Palmo-Plantar hyperkeratosis, intellectual disability, and spastic paraplegia in two maternal half brothers: further evidence for an X-linked inheritance.
In 1983, Fitzsimmons et al. reported four brothers with an unrecognized disorder characterized by intellectual disability, spastic paraplegia, and palmo-plantar hyperkeratosis (OMIM 309500). In this report, we describe a family in which two males, maternal half-brothers, had learning disabilities. Both patients also showed spasticity in the lower limbs and palmo-plantar hyperkeratosis. The mother of the affected boys had learning difficulties but did not show any dermatological symptoms. This report confirms that the association of features reported by Fitzsimmons et al. is a distinct entity and further suggests an X-linked mode of inheritance.


Hepatic stimulator substance alleviates toxin-induced and immune-mediated liver injury and fibrosis in rats.
Liver fibrosis is a common scarring response to chronic liver injury. It is a precursor to cirrhosis and liver carcinoma. Hepatic stimulator substance (HSS), a known liver-specific but species-nonspecific growth factor, has been shown to protect hepatocytes from various toxins. We have investigated the effects of HSS therapy on carbon tetrachloride (CCl(4))-induced and porcine-serum-mediated hepatic injury and fibrosis. We hypothesize that HSS might attenuate liver injury and fibrosis by suppressing oxidative stress, down-regulating profibrogenic factors, and blocking HSCs activation. This report demonstrated that HSS therapy diminished α-smooth muscle actin expression, decreased intrahepatic reactive oxygen species (ROS) level, and down-regulated transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF)-BB, and tissue inhibitor of metalloproteinase (TIMP)-1 expression. In addition, HSS treatment significantly protected the liver from injury by improving liver function tests and histological architecture of the liver. These results provided novel insights into the mechanisms of HSS in the protection of the liver. Our results suggested that HSS might be a therapeutic antifibrotic agent for the treatment of liver fibrosis.


Non-coding RNA-mediated epigenetic alterations in Grave's ophthalmopathy: A scoping systematic review.
It is becoming more and more apparent that Grave's Ophthalmopathy (GO) pathogenesis may be aided by epigenetic processes such as DNA methylation modifications, histone tail covalent modifications, and non-coding RNA (ncRNA)-based epigenetic processes. In the present study, we aimed to focus more on the miRNAs rather than lncRNAs due to lack of investigations on these non-coding RNAs and their role in GO's pathogenesis. A six-stage methodology framework and the PRISMA recommendation were used to conduct this scoping review. A comprehensive search was conducted across seven databases to discover relevant papers published until February 2022. The data extraction separately, and quantitative and qualitative analyses were conducted. A total of 20 articles were found to meet inclusion criteria. According to the results, ncRNA were involved in the regulation of inflammation (miR-146a, LPAL2/miR-1287-5p axis, LINC01820:13/hsa miR-27b-3p axis, and ENST00000499452/hsa-miR-27a-3p axis), regulation of T cell functions (miR-146a/miR-183/miR-96), regulation of glycosaminoglycan aggregation and fibrosis (miR-146a/miR-21), glucocorticoid sensitivity (miR-224-5p), lipid accumulation and adipogenesis (miR-27a/miR-27b/miR-130a), oxidative stress and angiogenesis (miR-199a), and orbital fibroblast proliferation (miR-21/miR-146a/miR-155). Eleven miRNAs (miR-146a/miR-224-5p/miR-Let7d-5p/miR-96-5p/miR-301a-3p/miR-21-5p) were also indicated to have the capacity to be used as biomarkers. Regardless of the fact that there is significant documentation of ncRNA-mediated epigenetic dysfunction in GO, additional study is needed to thoroughly comprehend the epigenetic connections concerned in disease pathogenesis, paving the way for novel diagnostic and prognostic tools for epigenetic therapies among the patients.


Adjuvant-induced arthritis is a relevant model to mimic coronary and myocardial impairments in rheumatoid arthritis.
To determine if the adjuvant-induced arthritis model reproduced coronary and cardiac impairments observed in rheumatoid arthritis patients. The link between disease activity and circulating levels of angiotensin II and endothelin-1 have been studied, as well as the myocardial susceptibility to ischemia. At the acute inflammatory phase, coronary reactivity was assessed in isolated arteries, and cardiac function was studied in isolated perfused hearts, before and after global ischemia/reperfusion. Ischemic insult was evaluated by the infarct size, lactate dehydrogenase and creatine phosphokinase levels in coronary effluents. Cardiac myeloperoxidase activity was measured, as well as angiotensin II and endothelin-1 levels. Compared to controls, adjuvant-induced arthritis had reduced coronary Acetylcholine-induced relaxation associated with cardiac hypertrophy, both being correlated with plasma levels of endothelin-1 and angiotensin II, and arthritis score. Although cardiac function at baseline was similar from controls, adjuvant-induced arthritis rats exhibited lower cardiac functional recovery, increased myeloperoxidase activity, higher infarct size and creatine phosphokinase levels after ischemia/reperfusion. The adjuvant-induced arthritis model displays coronary endothelial dysfunction associated with myocardial hypertrophy and a reduced tolerance to ischemia. This model might be useful for deciphering the pathophysiology of cardiac dysfunction in rheumatoid arthritis and paves the way for studying the role of endothelin-1 and angiotensin II.


Separation of Hydrogen from Carbon Dioxide through Porous Ceramics.
The gas permeability of α-alumina, yttria-stabilized zirconia (YSZ), and silicon carbide porous ceramics toward H₂, CO₂, and H₂-CO₂ mixtures were investigated at room temperature. The permeation of H₂ and CO₂ single gases occurred above a critical pressure gradient, which was smaller for H₂ gas than for CO₂ gas. When the Knudsen number (λ/r ratio, λ: molecular mean free path, r: pore radius) of a single gas was larger than unity, Knudsen flow became the dominant gas transportation process. The H₂ fraction for the mixed gas of (20%-80%) H₂-(80%-20%) CO₂ through porous Al₂O₃, YSZ, and SiC approached unity with decreasing pressure gradient. The high fraction of H₂ gas was closely related to the difference in the critical pressure gradient values of H₂ and CO₂ single gas, the inlet mixed gas composition, and the gas flow mechanism of the mixed gas. Moisture in the atmosphere adsorbed easily on the porous ceramics and affected the critical pressure gradient, leading to the increased selectivity of H₂ gas.


Fast responses to images of animate and inanimate objects in the nonhuman primate amygdala.
Visual information reaches the amygdala through the various stages of the ventral visual stream. There is, however, evidence that a fast subcortical pathway for the processing of emotional visual input exists. To explore the presence of this pathway in primates, we recorded local field potentials in the amygdala of four rhesus monkeys during a passive fixation task showing images of ten object categories. Additionally, in one of the monkeys we also obtained multi-unit spiking activity during the same task. We observed remarkably fast medium and high gamma responses in the amygdala of the four monkeys. These responses were selective for the different stimulus categories, showed within-category selectivity, and peaked as early as 60 ms after stimulus onset. Multi-unit responses in the amygdala were lagging the gamma responses by about 40 ms. Thus, these observations add further evidence that selective visual information reaches the amygdala of nonhuman primates through a very fast route.


Clean Up after Yourself.
NLRP3 inflammasome activation is accompanied by induction of mitochondrial damage. In the current issue of Cell, Zhong et al. describe an intracellular mechanism orchestrated by NF-κB to remove inflammasome-activating damaged mitochondria and prevent pathologic inflammation.


Tailoring molecularly imprinted polymer beads for alternariol recognition and analysis by a screening with mycotoxin surrogates.
Molecularly imprinted porous polymer microspheres have been prepared for selective binding of alternariol (AOH), a phenolic mycotoxin produced by Alternaria fungi. In order to lead the synthesis of recognition materials, four original AOH surrogates have been designed, prepared and characterized. They bear different number of phenol groups in various positions and different degree of O-methylation on the dibenzo[b,d]pyran-6-one skeleton. A comprehensive library of mixtures of basic, acidic or neutral monomers, with divinylbenzene or ethyleneglycol dimethacrylate as cross-linkers, were polymerized at a small scale in the presence of the four molecular mimics of the toxin molecule. This polymer screening has allowed selection of the optimal composition of the microbeads (N-(2-aminoethyl)methacrylamide, EAMA, and ethylene glycol dimethacrylate). The latter are able to bind AOH in water-acetonitrile (80:20, v/v) with an affinity constant of 109±10mM(-1) and a total number of binding sites of 35±2μmolg(-1), being alternariol monomethylether the only competitor species. Moreover, (1)H NMR titrations have unveiled a 1:2 surrogate-to-EAMA stoichiometry, the exact interaction sites and a binding constant of 1.5×10(4)M(-2). A molecularly imprinted solid phase extraction (MISPE) method has been optimized for selective isolation of the mycotoxin from aqueous samples upon a discriminating wash with 3mL of acetonitrile/water (20:80, v/v) followed by determination by HPLC with fluorescence detection. The method has been applied, in combination to ultrasound-assisted extraction, to the analysis of AOH in tomato samples fortified with the mycotoxin at five concentration levels (33-110μgkg(-1)), with recoveries in the range of 81-103% (RSD n=6). To the best of our knowledge, this is the first imprinted material capable of molecularly recognizing this widespread food contaminant.


Service provision for patients with ALS/MND: a cost-effective multidisciplinary approach.
Optimal management of patients with ALS/MND requires a team approach, with early referral to paramedical services for clinical assessment and prompt intervention. As the condition progresses, a flexible approach to management must be adopted by the medical team, with an ability to intervene at very short notice. We have developed an efficient multi-disciplinary clinic that services the ALS/MND population of Ireland by combining the existing infrastructure of community services with a hospital-based specialist clinic. The clinic operates on a weekly basis, and is staffed by a core team including a neurologist, a liaison nurse, and the director of the ALS/MND Association. On-site and same-day physiotherapy, occupational therapy and speech therapy is available, as is pulmonary evaluation. All patients utilising the clinical services are automatically included on the Irish Register of Motor Neurone Disease, and are tracked by the liaison nurse. The core members of the clinic interact regularly with paramedical staff within the community, ensuring that necessary community services are made available within 1-2 weeks of the clinic visit. Equipment necessary for the patient's well being is made available free of charge by the Irish Motor Neurone Disease Association, following an appropriate request from the regional para-medical staff. We have thus demonstrated that an effective multi- disciplinary care service for ALS/MND can be developed at modest cost by close personal liaison between the existing health care structures and core members of a multidisciplinary team.


Sex, age, and race/ethnicity do not modify the effectiveness of a diet intervention among family members of hospitalized cardiovascular disease patients.
To determine whether effectiveness of a diet intervention for family members of cardiovascular disease patients varies by participant sex, race/ethnicity, or age because these characteristics have been associated with unique barriers to diet change. Randomized controlled trial. University medical center. Healthy adult family members of patients hospitalized with cardiovascular disease (n = 501; 66% women; 36% racial/ethnic minorities; mean age 48 years). A special screening and educational intervention (SI) vs control intervention (CI) to reduce dietary saturated fat and cholesterol intake throughout 1 year. Absolute change in MEDFICTS (meats, eggs, dairy, fried foods, fat in baked goods, convenience foods, fats added at the table and snacks) diet score, saturated fat, and dietary cholesterol in the SI vs CI from baseline to 1 year. t tests stratified by sex, race/ethnicity, and age group; linear regression. Significance set at P < .05. The SI was effective to improve MEDFICTS score independent of sex, race/ethnicity, and age group (β = -6.7; P < .001). There was no interaction between the SI and sex (β = .9; P = .84), race/ethnicity (β = -1.1; P = .81), or age group (β = -.6; P = .89) on change in MEDFICTS score or change in saturated fat or dietary cholesterol intake from baseline to 1 year. Results support the potential for a hospital-based screening and education program to improve diet in diverse populations of cardiovascular disease patient family members.


Gender and age related differences in left ventricular function and geometry with focus on the long axis.
To study age and gender related alterations in left ventricular (LV) long axis function. Eighty-two healthy individuals from the general population in three age groups were investigated. LV long axis and short axis function and dimensions were studied with echocardiographic M-mode and two-dimensional technique. The most prominent age related differences were observed in LV long axis function, whereas only minor alterations in short axis function were noticed. Both systolic and diastolic long axis function decreased with advancing age; maximal systolic velocity (r=0.61, p<0.0001), maximal early diastolic filling velocity (r=0.87, p<0.0001). The length of the long axis decreased with age, while the relative contraction amplitude was maintained. LV global and short axis measurements revealed significant differences between genders, males having generally larger dimensions, even when correcting for body surface area. Females exhibited a more pronounced remodelling process with advancing age. Functional age related changes in LV function are more prominent in the long axis, while differences between genders are more pronounced in short axis and in volume measurements. These findings might be of importance when remodelling processes are evaluated, as these appear to be different in men and women and also age related.


The key role of crystal boron in enhanced degradation of refractory contaminants using heterogeneous Fe3+/SPC system.
An origin Fenton-like system was discussed for the abatement of refractory contaminants. Sodium percarbonate (SPC) was utilized as the source of H2O2 and crystal boron (C-boron) was applied to enhance the activation of H2O2. Under the conditions of 0.50 mM Fe3+, 0.34 mM SPC, and heterogeneous catalysis using 100 mg L-1 C-boron, four target pollutants, at the initial concentrations of 20 μM, could be efficiently degraded by the Fenton-like system, with a degradation rate within 20 min up to 81.1% (aspirin, ASA), 92.8% (nitrobenzene, NB), 94.7% (flunixin meglumine, FMME), and 94.3% (benzoic acid, BA) respectively and total organic carbon removal up to 25.0%. The increase of Fe2+ concentration indicated that the conversion of Fe2+/Fe3+ was remarkably promoted by C-boron. Degradation reactions at acidic pH were comparatively fast, with pH-dependent kobs of 9.9 × 10-2 min-1 (ASA), 1.5 × 10-1 min-1 (NB), 1.7 × 10-1 min-1 (FMME), and 1.9 × 10-1 min-1 (BA), whereas those at neutral and alkaline pH were slower. Furthermore, reactive oxygen species including ·OH, 1O2, and O2·- were identified by in-situ electron paramagnetic resonance tests. The contribution ratios of ·OH turned out to be about 71.3-86.7% for the decomposition of four contaminants. The elimination of natural organic matter and the performance of material recycling highlighted the potential for its application in water treatment. The inhibition rate of Chlorella pyrenoidosa reached 211.9% in the C-boron/Fe3+/SPC system. The relatively high algae toxicity limited its application scope, which requires additional research to resolve.


Assessing mucin expression and function in human ocular surface epithelia in vivo and in vitro.
Mucins of the corneal and conjunctival epithelia are necessary for the protection of the ocular surface against desiccation, pathogen access, and injury. Detection and quantification of mucins is important for the understanding of ocular surface diseases that cause impaired vision and, in advanced stages, blindness. Advances in the field of molecular biology have made it possible to study membrane mucins and their associated O-glycans in established cell culture models of human ocular surface epithelia. This chapter discusses procedures to detect and quantify mucin RNA and protein in biological samples, as well as methods to experimentally manipulate the epithelia in culture by shRNA, to understand the function of specific mucins. Example protocols are provided to evaluate the role of ocular surface mucins in mucosal barrier function and bacteria-host interactions.


[Clinical evaluation of pirozadil, administered continuously over four and a half years, in patients with hyperlipoproteinemia type IIa].
With the goal to evaluate the long term efficacy and tolerance of pirozadil, 20 patients with hypercholesterolemia (type II a hyperlipoproteinemia) received this drug for 4.5 years. Lipidic parameters and the appearance of subjective manifestations related to the drug were periodically controlled. The triglyceride concentration (34%), total cholesterol (24%) and LDL-cholesterol (47%) decreased after 6 months of treatment with 1.5 to 2 g/day of pirozadil. These changes were more manifest during the second semester of therapy and did not show important oscolations in subsequent controls. Adverse effects, indicating the withdrawal of the drug were not encountered. Three patients had minor and transient epigastralgias. Taken as a whole, these results reinforce the usefulness of pirozadil in treating patients with hypercholesterolemias.


Perception of quality of life among anesthesiologists and non-anesthesiologists.
Literature points out routine factors with negative impact on anesthesiologists' quality of life. This study aims to compare the perception of quality of life of anesthesiologists and non-anesthesiologists. Transversal study based on three specific questionnaires (epidemiological, WHOQOL-BREF and SF-12®) applied in anesthesiologists (Group A) and non-anesthesiologists (Group NA), of a general university hospital and a third group of anesthesiologists from inner state (Group I). The analysis of epidemiological variables and the ones related to quality of life domains of WHOQOL were interpreted by multivariate analysis (SPSS program). The number of WHOQOL-BREF respondents were: Group A=67; Group NA=69; Group I=53. The anesthesiologists from Group I were excluded from the study due to an inadequate sample for statistical analysis. The total number of respondents to check the SF-12® score was 61 in Group A and 68 in Group NA. For the WHOQOL-BREF tool, the physical domain scores were 72.97±11.78 for Group A and 77.17±10.85 for Group NA (p<0.05); the psychological domain scores were 66.44±13.66 for Group A and 71.79±11.48 for Group NA (p<0.05); the social relationship domain scores were 64.67±19.08 for Group A and 73.36±15.37 for Group NA (p<0.01); and the environment domain scores were 68.14±11.56 for Group A and 72.37±10.07 for Group NA (p<0.05). In SF-12®, both physical and mental components did not show statistical differences. The perception of the anesthesiologists' quality of life was consistently inferior to other physicians in general, for the studied sample.


Relative quantification based on logistic models for individual polymerase chain reactions.
The quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) technology measures molecular variations in specific biomarkers. Relative quantification determines the target expression relative to an external standard or reference sample and should be adjusted for the PCR efficiencies actually achieved. More accurate methods of estimating PCR efficiency require a number of serial dilutions of the target sample, which is not generally feasible for clinical specimens. Alternatively, the efficiency of a single reaction may be estimated by considering kinetic data from this reaction. The current methods of estimating individual reaction efficiency require finding its exponential phase, which may affect the accuracy and precision of efficiency estimates. Thus, a model adequately representing all available kinetic RT-PCR data is preferable, but no such model is currently in use for relative quantification. In this work, we use a logistic model for all kinetic data from each RT-PCR and propose a new method of efficiency-adjusted relative quantification based on the estimates from the fitted logistic models. This method allows incorporating multiple replicates and possibly multiple reference ('housekeeping') genes for estimating relative expression and corresponding confidence interval. Real kinetic RT-PCR data are used to compare the proposed and standard methods. The methods are applied to the clinical data from the ongoing study of guanylyl cyclase C as a biomarker for colorectal cancer.


Cortisol metabolism in lymphocytes from cancer-bearing patients.
A study was conducted to determine the pattern of cortisol metabolism by lymphocytes obtained from four groups of subjects: 27 male and female patients suffering from various types of malignancy other than malignancy of lymphatic tissues; and 26 healthy male and female controls. Known concentrations of cells were incubated with 1,2-3H-cortisol and the products were isolated by thin-layer and paper chromatography. Three metabolites were found to be produced by lymphocytes from both normal and cancer-bearing patients: 20alpha-hydroxycortisol, 20beta-hydroxycortisol, and tetrahydrocortisol. Cells from the female control group were found to be more active than those from the male controls, while cells from cancer-bearing patients were markedly more active than the normal cells, regardless of sex. It is suggested that this finding of increased metabolism of cortisol by lymphocytes from patients with different types of malignancy other than lymphoma may provide the basis for a new diagnostic aid.


Impact of Rural Residence on Warfarin Use and Clinical Events in Patients with Non-Valvular Atrial Fibrillation: A Canadian Population Based Study.
We studied whether anticoagulant use and outcomes differed between rural versus urban Canadian non-valvular atrial fibrillation (NVAF) patients prior to the introduction of direct oral anticoagulant drugs. Retrospective cohort study of 25,284 adult Albertans with NVAF between April 1, 1999 and December 31, 2008. Compared to urban patients, rural patients were older (p = 0.0009) and had more comorbidities but lower bleeding risk at baseline. In the first year after NVAF diagnosis, urban patients were less likely to be hospitalized (aOR 0.82, 95%CI 0.77-0.89) or have an emergency department visit for any reason (aOR 0.61, 95%CI 0.56-0.66) but warfarin dispensation rates (72.2% vs 71.8% at 365 days, p = 0.98) and clinical outcomes were similar: 7.8% died in both groups, 3.2% rural vs. 2.8% urban had a stroke or systemic embolism (SSE) (aOR 0.92, 95%CI 0.77-1.11), and 6.6% vs. 5.7% (aOR 0.93, 95%CI 0.81-1.06) had a bleed. Baseline SSE risk did not impact warfarin dispensation (73.0% in those with high vs. 72.8% in those with low CHADS2 score, p = 0.85) but patients at higher baseline bleeding risk were less likely to be using warfarin (69.2% high vs. 73.6% low HASBLED score, p<0.0001) in the first 365 days after diagnosis. In warfarin users, bleeding was more frequent (7.5% vs 6.2%, aHR 1.51 [95%CI 1.33-1.72]) but death or SSE was less frequent (7.0% vs 18.1%, aHR 0.60 [0.54-0.66]). Warfarin use and clinical event rates did not differ between rural and urban NVAF patients in a universal access publically-funded healthcare system.


The learning of isometric force time scales is differentially influenced by constant and variable practice.
This experiment was set up to investigate the influence of constant and variable practice on performance accuracy and the time- and frequency-dependent structure of the force output dynamics in the learning of an irregular isometric force pattern. Traditional approaches to the variability of practice hypothesis have demonstrated benefits of task-induced variability at the outcome level of behavior, but there have been limited investigations of the effect of practice conditions on movement execution and particularly the multiple time scale processes of force output. During the practice phase, variability was induced along the force-time dimension of the target pattern for the variable practice condition (different wave forms), but the wave forms exhibited the same distributional properties of the frequency content (1/f noise: β = -1.5) as the constant practice condition. The results showed that both practice conditions exhibited similar reductions in task error as a function of practice. However, constant practice produced greater changes in the time- and frequency-dependent properties of force output than variable practice, including a higher relative change in the contribution from faster (4-12 Hz) time scale mechanisms. Generalization tests to novel target patterns revealed that the task dynamics had a greater influence than the effect of practice conditions. Collectively, the findings support the adaptive nature of force output structure and the perspective that practice conditions can produce differential effects on the outcome and execution levels of motor behavior.


Primary osteosarcoma of the liver.
Extraskeletal osteosarcomas are infrequent, and those that arise within parenchymal organs are very rare indeed. This case of a 71-year-old man with a primary osteosarcoma of the liver is the second reported in man. Pathologic findings, including ultrastructural features, at surgery and autopsy are presented. The differential diagnosis is discussed in detail.


Minimally invasive treatment for isolated internal iliac artery aneurysms preserving superior gluteal artery flow.
To prevent buttock claudication, we performed endovascular aortic aneurysm repair (EVAR) for isolated internal iliac aneurysms (IIAAs) with selective preservation of the superior gluteal artery (SGA) flow. This study evaluates early clinical outcomes of this treatment. We retrospectively evaluated 6 patients with isolated IIAA who underwent EVAR under local anesthesia between October 2017 and July 2018 at Tokyo Women's Medical University Hospital. We used self-expanding stent grafts to exclude the IIAA while preserving SGA flow. If necessary, we occluded the inferior gluteal artery and other branches with vascular plugs to prevent type II endoleak. The mean proximal neck diameter and length of the IIAAs to be 9.4 ± 2.4 mm and 17.7 ± 11.3 mm. The mean diameter of the SGA was 6.5 ± 0.9 mm. There were no procedural complications, and the mean procedure time was 84 ± 24 min. All patients were free from buttock claudication at follow-up. Postoperative computed tomography demonstrated a 100% primary patency rate of the SGA stent graft: there was no case of migration or endoleak. EVAR for IIAAs with SGA flow preservation shows favorable early clinical outcomes. To prevent buttock claudication, SGA flow is necessary and sufficient. This novel approach is less invasive compared to conventional IIAA repair.


A comprehensive review on isolated and non-isolated converter configuration and fast charging technology: For battery and plug in hybrid electric vehicle.
Electric vehicle systems are a promising future transportation system because they play an important role in reducing atmospheric carbon emission and have become a focal point of research and development in the present era. The emerging fast charging technology has the ability to have refueling experiences comparable to gasoline cars. This article discusses existing electric vehicle charging infrastructure with a particular emphasis on rapid charging technologies, which would be needed to meet current and potential EV refueling requirements. Various dc-dc converter topologies for battery electric and plug-in hybrid vehicles are compared and contrasted in this article in terms of performance, output power, current ripples, voltage ripples, conduction loss, recovery loss, switching frequency loss, reliability, durability, and cost. The architecture, benefits, and drawbacks of AC-DC and DC-DC converter topologies for rapid charging stations are also discussed in this article. Furthermore, this study addresses the crucial problems and difficulties associated with electric vehicle converters for direct current rapid charging. Eventually, technical and relevant contributions are provided for an electric vehicle system development.


Modified interdigitated arrays by novel poly(1,8-diaminonaphthalene)/carbon nanotubes composite for selective detection of mercury(II).
This study describes a novel type of interdigitated arrays (IDA), microfabricated by electropolymerizing structured Poly(1,8-diaminonaphthalene)/functionalized multi-walled carbon nanotubes (PDAN/CNT) thin film onto a silicon chip for square wave voltammetry (SWV) multi-element heavy metal ion detection. The structure of PDAN/CNT was characterized by Raman, FE-SEM and AFM techniques. Analysed experiments reveal that the uptake of Hg(2+) by PDAN/CNT is quite specific and it can be used advantageously for electrochemical sensing of Hg(2+) thanks to original feature of (Hg(2+)/Hg(2)(2+)) redox potential with the respect to that of PDAN/CNT. As-developed IDA type electrode can extend its utility in other sensing applications.


Phosducin rs12402521 polymorphism predicts development of hypertension in young subjects with overweight or obesity.
The G-protein regulator phosducin has been shown to be associated with stress-dependent blood pressure, but whether obesity is a modulator of the relationship between phosducin and risk of hypertension is unknown. We studied the effect of two phosducin polymorphisms on risk of hypertension in 273 overweight or obese (Ov-Ob) young-to-middle-age participants from the HARVEST and 287 normal weight (NW) participants. Genotyping of phosducin SNPs rs12402521 and rs6672836 was performed by real time PCR. For rs12402521, 64.6% of the participants were homozygous for the G allele, 27.9% heterozygous, and 7.5% homozygous for the A allele. During 7.7 years of follow-up, 339 subjects developed hypertension. In a Cox multivariable model, carriers of the A allele had a 1.28 (95% CI,1.00-1.63, p = 0.046) increased risk of hypertension. However, increased incidence of hypertension associated with A allele (AA + AG, 79% and GG, 59%, p = 0.001) was observed only among Ov-Ob individuals with a hazard ratio of 1.60 (95% CI, 1.13-2.21, p = 0.007) whereas in NW subjects the incidence of hypertension did not differ by genotype (56% in both groups). In the whole cohort, there was a significant interaction of phosducin genotype with body mass index on the risk of hypertension (p = 0.012). For SNP rs6672836 no association was found with incident hypertension. No haplotype effect was detected on the risk of hypertension. These data suggest that phosducin rs12402521 polymorphism is an important genetic predictor of obesity-related hypertension. In Ov-Ob carriers of the A allele aggressive nonpharmacological measures should be implemented.


Update on Maxillary Sinus Augmentation.
Implant stability is critical to implant success, and the amount of available bone is vital to achieving that end. Because of low-lying maxillary sinuses, adequate alveolar height on the posterior maxilla is often lacking in many patients in need of implant replacement. This chapter reviews both the traditional lateral sinus lift maxillary approach to achieve vertical augmentation as well as the transcrestal osteotome intraoral approach. A discussion of osseodensification will also be mentioned as an alternative approach.


Variations in granulocyte colony forming cell numbers in adult blood.
Blood granulocyte colony forming units (CFU-C) were studied in normal adults to establish: (i) a normal range; (ii) variability due to the culture technique; (iii) variability of blood CFU-C within individuals. Thirty men studied had 98 (range 8--300) CFU-C X 10(3)/1, and 28 women studied had 44 (range 0--260) CFU-C X 10(3)/1. This difference was significant (P less than 0.001). There was also a significant sex difference in the total number of cells forming colonies and clusters per litre; and in the incidence of colony formers and of cluster formers in buffy coat and mononuclear cell blood fractions. CFU-C were assayed in four subjects over a 10 week period. When buffy coat cells were used as a source of colony stimulation the week to week variation in the combined growth of the four subjects was wide (+/- 36%) but with conditioned medium the variation was smaller (+/- 14%). In all subjects colony and cluster growth varied in the same way (r = 0.77, P = .001) but there was no correlation with the total leucocyte count. A 3--4 week cyclical change in CFU-C/1 was found which was independent of the variation inherent in the technique. The physiological significance of the sex difference and the apparent cyclical changes in blood CFU-C are not explained, but the results emphasize the wide fluctuations in CFU-C that may occur in normal individuals.


Leucine increases mitochondrial metabolism and lipid content without altering insulin signaling in myotubes.
Elevated circulating branched-chain amino acids (BCAA) such as leucine have been consistently correlated with increasing severity of insulin resistance across numerous populations. BCAA may promote insulin resistance through either mTOR-mediated suppression of insulin receptor substrate-1 or through the accumulation of toxic BCAA catabolites. Although the link between circulating BCAA and insulin resistance has been consistent, it has yet to be concluded if BCAA causally contribute to the development or worsening of insulin resistance. This work investigated the effect of leucine both with and without varying levels of insulin resistance on metabolism, metabolic gene expression, and insulin signaling. C2C12 myotubes were treated with and without varied concentrations of leucine up to 2 mM for 24 h both with and without varied levels of insulin resistance. Gene and protein expression were measured via qRT-PCR and Western blot, respectively. Mitochondrial metabolism was measured via O2 consumption. Leucine at 2 mM increased oxidative metabolism as well as gene expression of mitochondrial biogenesis, which was associated with increased cellular lipid content. Despite increased lipid content of leucine-treated cells, neither acute nor chronic leucine treatment at 2 mM affected insulin signaling in insulin sensitive, mildly insulin resistant, or severely insulin resistant cells. Similarly, leucine at lower concentrations (0.25 mM, 0.5 mM, and 1 mM) did not alter insulin signaling either, regardless of insulin resistance. Leucine appears to improve myotube oxidative metabolism and related metabolic gene expression. And despite increased lipid content of leucine-treated cells, leucine does not appear to alter insulin sensitivity either acutely or chronically, regardless of level of insulin resistance.


Serum Adenosine Deaminase Levels and Human Papillomavirus as Prognostic and Predictive Factors for Laryngeal and Pharyngeal Carcinomas.
Head and neck cancer is one of the most common cancers in the world, accounting for up to 30-40% malignancies in India. Research is always on the lookout for parameters that help in early diagnosis of such disease and to explore the possibility of discovering such parameters that would assist in management of the disease by its potential to predict and prognosticate the disease. To estimate serum ADA levels and to correlate with response to therapy and also to correlate between different clinical stages and serum ADA levels and to correlate HPV status to response to therapy. A prospective cohort study. 30 patients who were diagnosed with squamous cell carcinoma of the oropharynx, hypopharynx and larynx were considered in this study. The pre and post treatment values of serum ADA was estimated in these patients and the tumour was assessed for HPV status. The difference in the in the serum ADA levels before and after treatment was 9.982 which was statistically significant with a p value of < 0.001. HPV positive status and response to therapy in the form of recurrence shows a p value of 0.485 which is not statistically significant. Serum ADA level can be used as a parameter to assess the severity of the disease and the response to treatment in cases of carcinoma of the oropharynx, hypopharynx and larynx. HPV status of the disease has its limitation in prediction and prognosis of the disease.


Bioactivity-guided isolation of cyclooxygenase-2 inhibitors from Saussurea obvallata (DC.) Edgew. Using affinity solid phase extraction assay.
Saussurea obvallata (DC.) Edgew. is a traditional Tibetan medicine used for the treatment of inflammation-related diseases, but the scientific validation was very limited. This study aimed to rapid screen and targeted isolate cyclooxygenase-2 (COX-2) inhibitors from S. obvallata extract. An efficient ligand-fishing method based on affinity solid phase extraction (A-SPE) combining with HPLC was developed. The identified COX-2 inhibitors were separated using preparative liquid chromatography. In vitro COX-2 inhibition assays were employed to confirm the inhibitory activities of the isolated compounds. In addition, the effect of the isolated compounds on the production of prostaglandin E2 (PGE2) and the expression of COX-2 in LPS-induced RAW 264.7 were evaluated. A total of four phenylpropanoids, isolariciresinol, syringaresinol, pinoresinol and balanophonin were targeted isolated as COX-2 inhibitors with IC50 values of 36.4 ± 2.6 μM, 23.1 ± 1.8 μM, 3.6 ± 0.3 μM and 12.1 ± 0.9 μM, respectively. The isolated compounds significantly inhibited LPS-induced NO production in a dose-dependent manner. And, the results of the inhibitory effect on the release of PGE2 and the expression of COX-2 in LPS-induced macrophages were consistent with A-SPE analysis. The present work demonstrated that the developed A-SPE-HPLC method could successfully targeted isolated COX-2 inhibitors from S. obvallata extract. And, the isolation results indicated that the therapeutic effect of S. obvallata on inflammation-related diseases was partly based on the COX-2 active ingredients.


How long will honey bees (Apis mellifera L.) be stimulated by scent to revisit past-profitable forage sites?
Honey bees utilise floral food sources that vary temporally in their relative and absolute quality. Via a sophisticated colony organisation, a honey bee colony allocates its foragers such that the colony focuses on the most profitable forage sites while keeping track of changes within its foraging environment. One important mechanism of the allocation of foragers is the ability of experienced foragers to revisit past-profitable forage sites after a period of temporary dearth caused by, for example, inclement weather. The scent of past-profitable forage within the colony brought back by other foragers is sufficient to reactivate these experienced foragers. Here I determine for how long bees react to the scent of a past-profitable forage site. I show that the ability of foragers to revisit the location of a past-profitable food source diminishes rapidly over a period of 10 days, until no forager reacts to the cue (scent). I discuss the implications of these findings with respect to the colony's ability to react rapidly to changing foraging conditions.


Biomarkers of Cardiac Dysfunction as Risk Factors in Cryptogenic Stroke.
It is unclear whether biomarkers of cardiac dysfunction are associated with cryptogenic stroke (CS). We retrospectively evaluated consecutive ischemic stroke patients. Patients underwent transthoracic echocardiography to evaluate left atrial diameter and the peak transmitral filling velocity/mean mitral annular velocity during early diastole (E/e'). Patent foramen ovale (PFO) and left atrial appendage flow velocity were evaluated by transesophageal echocardiography. We compared clinical characteristics and biomarkers of cardiac dysfunction (brain natriuretic peptide [BNP], left atrial diameter, E/e', and left atrial appendage flow velocity) between CS or CS without large PFO and other causative stroke subtypes. Among 1,514 patients with ischemic stroke, 264 patients were classified as having CS. Of these, transesophageal echocardiography revealed 27/158 (17%) large PFOs. In comparison, for the noncardioembolic stroke group, which consisted of large artery and small vessel subtypes, patients with CS without large PFO had higher log10 BNP (adjusted OR 2.70; 95% CI 1.92-3.78; p < 0.001), higher log10 E/e' (3.41; 1.21-13.15; p = 0.019), and lower left atrial appendage flow velocity (0.98; 0.97-1.00; p = 0.031). Left atrial diameter was similar for noncardioembolic stroke and CS without large PFO (p = 0.380). Cutoff values of BNP, E/e', and left atrial appendage flow velocity capable of distinguishing CS without large PFO from noncardioembolic stroke were 65.0 pg/mL (sensitivity 55.3%; specificity 70.9%), 13.0 (45.5%; 68.0%), and 46.0 cm/s (37.1%; 87.5%), respectively. Patients with CS without large PFO could have biomarkers of cardiac dysfunction.


Nursing students' assessment of pain and decision of triage for different ethnic groups: An experimental study.
Pain management is a priority in nursing care but little is known about the factors that affect nursing students' assessment of pain expressed by patients of different ethnic backgrounds. This study examined undergraduate nursing students' assessment of pain and decision of triage when pain was expressed in different languages and their relation to students' empathy and social identity. Comparison between students with and without clinical experience was also carried out. This is a cross-sectional quantitative design. This study took place at a university in Hong Kong. 74 female undergraduate nursing students. Students listened to eight audio recordings in which an individual expressed pain in one of the two dialects of Chinese, either Cantonese or Putonghua. For each dialect, two recordings depicted mild pain and two depicted severe pain. After listening to each recording, students rated the pain level and indicated their decision of triage. Subsequently, students completed a questionnaire that measured their empathy and social identity and reported their demographics. The data were analyzed by descriptive statistics, correlational analyses, and t-tests. Severe pain described in Putonghua was rated as more intense than that described in Cantonese but it was not classified as more urgent. Students with clinical experience tended to perceive mild pain as less painful and less urgent than those without clinical experience. For mild pain described in Cantonese, students with clinical experience evaluated it as more urgent than those without such experience. The empathy level of students with and without clinical experience was comparable. Students with more empathy, especially those without clinical experience, reported heightened perceived intensity of severe pain described in Putonghua. Nurse educators should note that empathy, social identity, and clinical experience may alter students' pain assessment of patients from different ethnicities. Pain education needs to be reinforced.


Extracellular annexin II is associated with divalent cation-dependent tumor cell-endothelial cell adhesion of metastatic RAW117 large-cell lymphoma cells.
Using fixed microvessel endothelial cell monolayers the molecules involved in the adhesion of liver-preferring murine RAW117 large cell lymphoma cells to murine liver-derived microvessel endothelial cells were identified by affinity isolation. Detergent lysates obtained from poorly (P) or highly (H10) liver-metastatic cells inhibited RAW117-H10 cell adhesion to hepatic sinusoidal endothelial (HSE) cell monolayers. Allowing detergent lysates of cell surface-labeled RAW117 cells to bind to fixed HSE cell monolayers and eluting the bound components indicated that several tumor cell surface molecules (approximately 70, approximately 35, approximately 32, approximately 22, and approximately 14 kDa) might be involved in RAW117 cell-HSE cell adhesion. The approximately 35 kDa component was cation dependent in its binding to target HSE cells. Increasing detergent concentration had no effect on binding of the approximately 35 kDa component to HSE cell monolayers, whereas treatment with 0.5 M NaCl resulted in its selective elution from HSE cells. Incubation of the HSE cell monolayers with detergent lysates from cell surface-labeled RAW117-H10 cells resulted in selective depletion of the approximately 35 kDa component, suggesting that the binding is saturable. This divalent cation-dependent molecule is one of the major tumor cell surface components bound by several types of endothelial cells and murine hepatocytes, whereas there was poor binding of this component to unfixed or fixed human red blood cells. The purified, partially (approximately 40%) sequenced molecule had amino acid sequence identity with murine but not bovine annexin II, indicating that it was not bound from the bovine serum used to grow RAW117 cells. Using antibodies specific for annexin II flow cytometry indicated equivalent amounts of annexin II are expressed on RAW117 cell surfaces in the absence or presence of excess EDTA, whereas annexin I was only found in low amounts on the surfaces of RAW117 cells. Annexin II antibodies inhibited by approximately 40-50% the adhesion of RAW117 tumor cells to live or fixed endothelial cells, and purified tumor cell surface fractions containing the approximately 35 kDa component partially inhibited (approximately 35%) RAW117 cell-HSE cell adhesion. The data indicate that annexin II is expressed on the extracellular surface of RAW117 cells, and cell surface-annexin II mediates a portion of the Ca(2+)-dependent RAW117 cell adhesion to liver microvessel endothelial cells.


Growth hormone treatment in human ageing: benefits and risks.
This paper will focus on the rationale of using Growth Hormone (GH) as an anti-ageing therapy in the healthy elderly with age-related decline in the activity of the GH/IGF-I axis, the so called "somatopause". Although the age-related decline in the activity of the GH/IGF-I axis is considered to contribute to age-related changes similar to those observed in Growth Hormone Deficient (GHD) adults, GH/IGF-I deficiency or resistance is also known to result in prolonged life expectancy, at least in animals. These data raise the question whether or not GH deficiency constitutes a beneficial adaptation to ageing and therefore requires no therapy. Moreover, although GH therapy has been shown to exert positive effects in GHD patients, its safety, efficacy and role in healthy elderly individuals is highly controversial. This review provides a comprehensive account of the implications of GH therapy in the ageing subject.


Five-Year Outcomes of Concomitant Maze Procedure Using Nitrous Oxide vs Argon-Based Cryoablation.
Cryoablation is effective for not only ablating the myocardium, but also maintaining the structure of the ablated tissue. However, data comparing nitrous oxide (N2O)-based and argon gas-based cryoprobes are limited. This study was a follow-up study of a single-center, prospective, randomized controlled trial in which 60 patients were randomly allocated to either the N2O group or the argon group. The primary endpoint of this study was sinus rhythm maintenance, and the key secondary endpoint was a composite of major adverse cardiovascular and cerebrovascular events (MACCEs) (ie, cardiac death, stroke, major bleeding, and readmission for heart failure). The baseline and operative characteristics of the patients in the N2O and argon groups were comparable. At the 5-year follow-up, the rate of sinus rhythm maintenance was 81.8% in the N2O group, whereas it was 78.5% in the argon group (P > .999). No significant differences in the rate of freedom from MACCEs (80.6% in the N2O group vs 81.9% in the argon group; P = .978) were observed at the 5-year follow-up. The left atrial volume index decreased over time from 114.65 mL/m2 to 65.74 mL/m2 (P < .0001) and reached similar values in the 2 groups (P = .279) at the 5-year follow-up. Both N2O- and argon gas-based cryoprobes showed similar rates of sinus rhythm maintenance and freedom from MACCEs at the 5-year follow-up. Both cryoprobes might have similar efficacy and safety in the arrested heart in the long term.


[Neurectodermal differentiation of extraskeletal myxoid chondrosarcoma: a classical feature?].
Extraskeletal myxoid chondrosarcoma (EMC) is a phenotypically and genotypically distinct entity with a protracted course. A documented case of an extraskeletal myxoid chondrosarcoma characterized by a t(9; 17) (q22; q11) translocation with a neuroendocrine and neural differentiation is reported.


Presence and fate of coliphages and enteric viruses in three wastewater treatment plants effluents and activated sludge from Tunisia.
The role of water in the transmission of infectious diseases is well defined; it may act as a reservoir of different types of pathogens. Enteric viruses can survive and persist for a long time in water, maintaining infectivity in many instances. This suggests the need to include virus detection in the evaluation of the microbiological quality of waters. In this study, enteric viruses (enteroviruses and hepatitis A virus (HAV)) were investigated by RT-PCR and coliphages (known as indicators of viral contamination) were enumerated with the double-layer technique agar in effluents and sewage sludge from three Tunisian wastewater treatment plants. The molecular detection of enteric viruses revealed 7.7% of positive activated sludge samples for enteroviruses. None of the samples was positive for HAV. Molecular virus detection threshold was estimated to be 10(3) PFU/100 ml. All samples contained high concentrations of coliphages except those of dry sludge. Reductions in the concentrations of bacteriophages attained by the wastewater treatment plants are of the order of magnitude as reductions described elsewhere. Peak concentrations in raw wastewater were associated with winter rains and suspended materials rate in analysed samples. Our data which is the first in North Africa showed that similar trends of coliphages distribution to other studies in other countries. No clear correlation between studied enteric viruses and coliphages concentration was proved. Coliphages abundance in collected samples should raise concerns about human enteric viruses transmission as these residues are reused in agricultural fields.


Dynamics of toxicity within different compartments of a peri-urban river subject to combined sewer overflow discharges.
Combined Sewer Overflows (CSO) in small peri-urban streams and rivers are potentially toxic for their biocenosis. Improving the management of CSO discharges requires better knowledge of their dynamics and toxicity. In view to characterizing this toxicity, we sampled the different compartments (benthic and hyporheic zone) of a peri-urban stream located near the city of Lyon in France. The samples were taken at different distances from a CSO and at three period characteristic of different hydrological conditions. Their toxic effects were assessed by bioassays on the dissolved fraction (D. magna, V. fisheri and B. calyciflorus bioassays) and on the particle fraction (V. fisheri and H. incongruens bioassays). The results highlighted significant toxicity of the particulate fraction for the benthic and hyporheic samples, in particular downstream of the CSO, but with high spatio-temporal variability. This variability can first be attributed to the variability of CSO discharge sampling as a function of season and rainfall, and the dynamics of polluted particles (trapping of transported particles in infiltration zones, mobilization during floods). These parameters play a fundamental role in the distribution of pollutants according to the geomorphology of stream facies. Regarding dissolved pollutants, the chemical exchanges taking place at the "water-sediment" interface trigger the transfer of pollutants from one phase to another, after which the dispersion of these pollutants is governed by hydraulic flows. Finally, critical zones and periods are identified for the peri-urban river toxicity studied: benthic sediments under mean flow downstream; hyporheic sediments after a storm event downstream, close to the CSO. Recommendations are made on the basis of the knowledge obtained to optimize the management of these discharges.


Investigating the performance of a novel cyclic rotating-bed biological reactor compared with a sequencing continuous-inflow reactor for biodegradation of catechol in wastewater.
The main objective of this study was to investigate the performance of a cyclic rotating-bed biological reactor (CRBR) in comparison to a sequencing continuous-inflow reactor (SCR) for the biodegradation and mineralization of catechol. Results showed that catechol degradation and mineralization in the SCR at the organic loading of 7.82kgCOD/m(3)d and the hydraulic retention time (HRT) of 9h were 28.2% and 10.3%, respectively. Under similar operating conditions to SCR, steady-state performance of CRBR with polyurethane foam (PUF) media for degradation and mineralization of catechol achieved was 98.7% and 97.9%, respectively. In comparison, the CRBR with 2H media attained average steady-state catechol degradation and mineralization of 89.1% and 83.6%, respectively, under similar conditions. Accordingly, the CRBR with PUF media presents a promising process for efficiently treating wastewater containing high concentrations of toxic, inhibitory and resistant compounds at a relatively short HRT.


Sensitivity of an infaunal amphipod, Eohaustorius estuarius, to acute waterborne exposures of 4-nonylphenol: evidence of a toxic hangover.
Three independent trials were conducted using mortality and burial as endpoints. Amphipod mean lethal concentration to 50% (LC50) was 227 microg/L. One-hour burial as a sublethal endpoint increased the sensitivity of the toxicity test by 40%; however, most amphipods that survived exposure were able to recover within 24 to 48 h. This toxic hangover was dose-dependent.


Growth-promoting effects of acidic and basic fibroblast growth factor on rabbit articular chondrocytes aging in culture.
Rabbit articular chondrocytes have a limited growth potential in vitro. After four passages in culture, chondrocytes have accomplished more than 50% of their life span. At this stage of culture, they are considered to be senescent-like, since a dramatic decrease in proliferative capacity and enhanced cell size and protein content are observed. These aged cells are, however, still able to respond to fibroblast growth factor (FGF). The addition of either acidic or basic FGF (10 ng/ml) to culture medium permitted an enhanced proliferation. The attenuation of FGF mitogenic activity during aging was not observed for both fractions. Moreover, when treated with acidic or basic FGF, aged chondrocytes had a smaller size and a lower protein content. The acidic FGF was less potent than the basic FGF in delaying the evolution of aged chondrocytes to senescence.


Policies to Create Healthier Food Environments in Canada: Experts' Evaluation and Prioritized Actions Using the Healthy Food Environment Policy Index (Food-EPI).
Food environment policies play a critical role in shaping food choices, diets, and health outcomes. This study endeavored to characterize and evaluate the current food environment policies in Canada using the Healthy Food Environment Policy Index (Food-EPI) to compare policies in place or under development in Canada as of 1 January 2017 to the most promising practices internationally. Evidence of policy implementation from the federal, provincial, and territorial governments was collated and verified by government stakeholders for 47 good practice indicators across 13 policy and infrastructure support domains. Canadian policies were rated by 71 experts from across Canada, and an aggregate score of national and subnational policies was created. Potential policy actions were identified and prioritized. Canadian governments scored 'high' compared to best practices for 3 indicators, 'moderate' for 14 indicators, 'low' for 25 indicators, and 'very little or none' for 4 indicators. Six policy and eight infrastructure support actions were prioritized as the most important and achievable. The Food-EPI identified some progress and considerable gaps in policy implementation in Canada, and highlights a particular need for greater attention to prioritized policies that can help to shift to a health-promoting food environment.


Lung injury and expression of p53 and p16 in Wistar rats induced by respirable chrysotile fiber dust from four primary areas of China.
Chrysotile products were widely used in daily life, and a large amount of respirable dust was produced in the process of production and application. At present, there was seldom research on the safety of chrysotile fiber dust, and whether its long-term inhalation can lead to lung cancer was unknown. In order to determine whether respirable chrysotile fiber dust of China caused lung cancer, four major chrysotile-producing mine areas in China were selected for this study. Chrysotile fibers were prepared into respirable dust. Particle size was measured by laser particle analysis, morphology was observed by scanning electron microscope, chrysotile fiber phase was analyzed by X-ray diffraction, trace chemical elements were identified by X-ray fluorescence, and the structure and the active groups of the dust were determined after grinding by Fourier transform infrared spectroscopy. Male Wistar rats were exposed to non-exposed intratracheal instillation with different concentrations of chrysotile fiber dust. The rats were weighed after 1, 3, and 6 months, then the lung tissues were separated, the lung morphology was observed, and the pulmonary index was calculated. Pathological changes in lung tissues were observed by optical microscope after the HE staining of tissues, and the gene expression of p53 and p16 was determined by reverse transcription polymerase chain reaction. First, the results showed that the particle sizes of the four fibers were less than 10 μm. Four primary areas of chrysotile had similar fibrous structure, arranged in fascicles, or mixed with thin chunks of material. Second, the elementary composition of the four fibers was mainly chrysotile, and the structure and the active groups of the grinding dust were not damaged. Third, the weights of the treated rats were obviously lower, and the lung weights and the pulmonary index increased significantly (P < 0.05). Fourth, the treated Wistar rat lung tissues revealed different degrees of congestion, edema, inflammatory cell infiltration, and mild fibrosis. Fifth, the p53 and p16 genes decreased in the Mangnai group after 1 month of exposure, and the other groups increased. The expression of p53 and p16 in each group decreased significantly after 6 months (P < 0.05). In conclusion, the respirable chrysotile fiber dust from the four primary areas of China had the risk of causing lung injury, and these changes may be related to the physical and chemical characteristics of chrysotile from different production areas.


Prevalence of eating disorders in female and male adolescents (14-15 years).
The main aim of the present study is to establish the prevalence of eating disorders (ED) in adolescents of both genders. To our knowledge, such data have not previously been published using both DSM-IV and DSM-III-R criteria. The study sample consisted of 1960 adolescents (1026 girls and 934 boys), 14-15 years of age. The participants completed the Survey for Eating Disorders (SEDs), including DSM-III-R and DSM-IV diagnoses for all subcategories of ED. Lifetime prevalence of any ED among girls was 17.9% anorexia nervosa (AN) 0.7%, bulimia nervosa (BN) 1.2%, binge eating disorder (BED) 1.5%, and EDs not otherwise specified (EDNOS) 14.6%. Corresponding numbers for boys for any ED is 6.5%, AN 0.2%, BN 0.4%, BED 0.9%, and EDNOS 5.0%. Our prevalence rates on AN, BN, and BED largely support previous school/community-based studies, while our figures on EDNOS were rather high. Generally, we found high numbers for boys with ED.


Effect of vitamin supplementation on polycystic ovary syndrome and key pathways implicated in its development: A Mendelian randomization study.
Many epidemiologic investigations have explored the relationship between viatmins and polycystic ovary syndrome (PCOS). However, the effectiveness of vitamin, vitamin-like nutrient, or mineral supplementation in reducing the risk of PCOS remains a subject of debate. To investigate the impact of plasma levels of vitamins A, B12, D, E, and K on PCOS and key pathways implicated in its development, namely, insulin resistance, hyperlipidemia, and obesity, through Mendelian randomization (MR) analysis. Single nucleotide polymorphisms associated with vitamin levels were selected from genome-wide association studies. The primary analysis was performed using the random-effects inverse-variance-weighted approach. Complementary analyses were conducted using the weighted median, MR-Egger, MR-robust adjusted profile score, and MR-PRESSO approaches. The results provided suggestive evidence of a decreased risk of PCOS with genetically predicted higher levels of vitamin E (odds ratio [OR] = 0.118; 95% confidence interval [CI]: 0.071-0.226; P < 0.001) and vitamin B12 (OR = 0.753, 95%CI: 0.568-0.998, P = 0.048). An association was observed between vitamin E levels and insulin resistance (OR = 0.977, 95%CI: 0.976-0.978, P < 0.001). Additionally, genetically predicted higher concentrations of vitamins E, D, and A were suggested to be associated with a decreased risk of hyperlipidemia. Increased vitamins K and B12 levels were linked to a lower obesity risk (OR = 0.917, 95%CI: 0.848-0.992, P = 0.031). The findings of this MR study suggest a causal relationship between increased vitamins A, D, E, K, and B12 levels and a reduced risk of PCOS or primary pathways implicated in its development.


First trimester screening for Down syndrome using free beta hCG, total hCG and PAPP-A: an exploratory study.
To investigate the potential utility of first trimester screening for Down syndrome using Free beta-hCG, total hCG and PAPP-A. Using estimates from the literature, a simulation study was undertaken to estimate the performance of tests incorporating, Free beta-hCG, total hCG and PAPP-A at gestations of 8-12 weeks. We used sensitivity analysis to assess the effect of departures from the assumed model. We estimate that detection rates in excess of 75% for a false positive rate (FPR) of 3% can be achieved with first trimester measures of PAPP-A, total hCG and Free beta-hCG at 8 weeks-the addition of total hCG adding 11%. Detection rates of around 90% for a FPR of 3% can be achieved through the inclusion of nuchal translucency (NT) at 12 weeks to these early first trimester biochemical markers. Our analysis indicates that the marginal benefit of adding total hCG diminishes rapidly with gestational age and that there is little benefit from adding total hCG later than 10 weeks of gestation. The performance of first trimester screening using early combinations of total hCG, Free beta-hCG and PAPP-A should be assessed in further studies.


Down-regulation of SMT3A gene expression in association with DNA synthesis induction after X-ray irradiation in nevoid basal cell carcinoma syndrome (NBCCS) cells.
Fibroblast cells derived from nevoid basal carcinoma syndrome (NBCCS) patients show increased levels of DNA synthesis after X-ray irradiation. Genes, whose expression is modulated in association with the DNA synthesis induction, were searched by using PCR-based mRNA differential display analysis in one of the NBCCS cell lines, NBCCS1 cells. Decreased levels of SMT3A gene expression were found in X-ray-irradiated NBCCS1 cells. This decrease was also shown by RT-PCR analysis in another cell line, NBCCS3 cells. In addition to NBCCS cells, normal fibroblast cells showed the DNA synthesis induction after X-ray irradiation when they were treated with antisense oligonucleotides (AO) for SMT3A. However, treatment of normal fibroblasts with the random oligonucleotides (RO) resulted in decreased levels of DNA synthesis after X-ray irradiation. Thus, down-regulation of SMT3A gene expression may be involved in the DNA synthesis induction after X-ray irradiation in the NBCCS cells at least tested.


The antigen receptor (NCCRP-1) on catfish and zebrafish nonspecific cytotoxic cells belongs to a new gene family characterized by an F-box-associated domain.
The catfish nonspecific cytotoxic cell receptor protein (NCCRP-1) provides an important function in target cell recognition and activation of cytotoxicity. This report identifies and characterizes a zebrafish orthologue of the catfish NCCRP-1. The zebrafish NCCRP-1 cDNA contains an open reading frame that encodes a predicted protein of 237 amino acids with a MW of 27 kDa and a pI of 5.5. Sequence similarities comparisons show that the NCCRP-1 receptors from these two phylogenetically distant species share a high degree of identity. These results suggested that NCCRP-1 performs a crucial function in innate immunity in teleosts. Further, a zebrafish 17-mer peptide corresponding to the catfish NCCRP-1 antigen-binding domain inhibited (catfish) cytotoxicity toward conventional tumor target cells (HL-60). These data appeared to indicate that the zebrafish NCCRP-1 protein may function as an antigen recognition molecule and, as such, may participate in innate immunity in teleosts. A homology search of the zebrafish NCCRP-1 protein revealed that it shares a significant level of identity with another group of proteins belonging to an F-box subfamily. These proteins share an F-box domain in the N terminus (not present in NCCRP-1) and an extremely conserved C-terminal region that has been termed the F-box-associated domain (FBA). The FBA is currently of unknown function. A new gene family is proposed in this work, based on similarities in the FBA sequences with the catfish and zebrafish NCCRP-1 peptides. This new gene family includes several F-box domain-containing proteins and a predicted C. elegans protein.


Rituximab Impairs B Cell Response But Not T Cell Response to COVID-19 Vaccine in Autoimmune Diseases.
Antibody response to the messenger RNA (mRNA) COVID-19 vaccine has been shown to be diminished in rituximab (RTX)-treated patients. We undertook this study to compare humoral and T cell responses between healthy controls, patients with autoimmune diseases treated with RTX, and those treated with other immunosuppressants, all of whom had been vaccinated with 2 doses of the mRNA COVID-19 vaccine. We performed anti-spike IgG and neutralization assays just before and 28 days after the second BNT162b2 (Pfizer-BioNTech) vaccine dose. The specific T cell response was assessed in activated CD4 and CD8 T cells using intracellular flow cytometry staining of cytokines (interferon-γ, tumor necrosis factor, and interleukin-2) after stimulation with SARS-CoV-2 spike peptide pools. A lower proportion of responders with neutralizing antibodies to the vaccine was observed in the RTX group (29%; n = 24) compared to the other immunosuppressants group (80%; n = 35) (P = 0.0001) and the healthy control group (92%; n = 26) (P < 0.0001). No patients treated with RTX in the last 6 months showed a response. Time since last infusion was the main factor influencing humoral response in RTX-treated patients. The functional CD4 and CD8 cellular responses to SARS-CoV-2 peptides for each single cytokine or polyfunctionality were not different in the RTX group compared to the other immunosuppressants group or the control group. In RTX-treated patients, the T cell response was not different between patients with and those without a humoral response. RTX induced a diminished antibody response to the mRNA COVID-19 vaccine, but the functional T cell response was not altered compared to healthy controls and autoimmune disease patients treated with other immunosuppressants. Further work is needed to assess the clinical protection granted by a functionally active T cell response in the absence of an anti-spike antibody response.


Effect of Divalent Ions on Electroosmotic Flow in Microchannels.
The electroosmotic flow (EOF) rate in fused silica microchannels is experimentally found to decrease when trace quantities of salts containing the divalent cations Ca(2+) and Mg(2+) are added to a constant ionic strength background electrolytic solution (BGE) flowing in a channel having negatively charged walls. Moreover, the observed effect is quantitatively different for the two ions Ca(2+) and Mg(2+). Since electrostatic interactions are identical for ions of the same valence modeled as point charges, a description of the electric double layer (EDL) based on the Poisson-Boltzmann equation alone cannot account for these experimental observations. New experimental observations on electroosmotic flow in presence of Ca(2+) and Mg(2+) are reported in this work. A site binding model that accounts for the chemical interactions of the BGE ions with the silica surface is developed. The model predictions are in good agreement with the experimental observations on divalent cations as well as data from the literature on how properties such as pH and ionic strength affect electroosmotic flow rates for a BGE with monovalent cations.


cDNA cloning and sequence determination of rat membrane-associated phospholipase A2.
Based on the partial amino acid sequences of membrane-associated phospholipase A2 (PLA2M), belonging to group II, purified from rat spleen, the cDNA encoding PLA2M was cloned by a new cloning strategy utilizing enzymatic cDNA amplification. At the N-terminus of the coded 146 residues, which were deduced from the cDNA sequence, the putative signal peptide was found despite the tight adherence of this enzyme to the membrane. The sequence of rat PLA2M exhibits 75% homology with that of human group II PLA2 in the protein-coding region. The result of RNA blot analysis showed that rat ileal mucosa contains the largest amount of the PLA2 transcript among the tissues examined.


Nanotubules on plant surfaces: chemical composition of epicuticular wax crystals on needles of Taxus baccata L.
Needles of Taxus baccata L. were covered with tubular epicuticular wax crystals varying in diameters (100 and 250 nm) and lengths (300-500 and 500-1000 nm) on the abaxial and adaxial surfaces, respectively. Various sampling protocols were employed to study the chemical composition of the needle waxes on three different levels of spatial resolution. First, a dipping extraction of whole needles yielded the total cuticular wax mixture consisting of very long chain fatty acids (21%), alkanediols (19%), phenyl esters (15%), and secondary alcohols (9%) together with small amounts of aldehydes, primary alcohols, alkanes, alkyl esters, and tocopherols. Second, waxes from both sides of the needle were sampled separately by brushing with CHCl3-soaked fabric glass. Both sides showed very similar qualitative composition, but differed drastically in quantitative aspects, with nonacosan-10-ol (18%) and alkanediols (33%) dominating the abaxial and adaxial waxes, respectively. Third, the epi- and intracuticular wax layers were selectively sampled by a combination of mechanical wax removal and brushing extraction. This provided direct evidence that the tubular wax crystals contained high percentages of nonacosane-4,10-diol and nonacosane-5,10-diol on the abaxial surface, and nonacosan-10-ol on the adaxial surface of the needles. Together with these compounds, relatively large amounts of fatty acids and smaller percentages of aldehydes, primary alcohols, alkyl esters, and alkanes co-crystallized in the epicuticular layer. In comparison, the intracuticular wax consisted of higher portions of cyclic constituents and aliphatics with relatively high polarity. The formation of the tubular crystals is discussed as a spontaneous physico-chemical process, involving the establishment of gradients between the epi- and intracuticular wax layers and local phase separation.


Measurement of renal pelvis pressures during endourologic procedures.
Twenty-five kidneys underwent nephrostomy puncture with placement of a pigtail catheter into an upper pole calyx for manometric recording during nephroscopy without a working sheath and with an Amplatz sheath with and without a Rutner adapter. Intrarenal pressures remained below 16 cm of water (H2O) at all times with the Amplatz sheath with or without a Rutner adapter, whereas without a sheath the pressures ranged from 15 to 31 cm H2O (i.e., pressures associated with significant pyelovenous and pyelosinus backflow). Similar results were obtained in monitoring intrarenal pressures during clinical procedures. A working sheath should be utilized for all percutaneous nephroscopic procedures to minimize the incidence of pyelovenous and pyelosinus backflow as well as of perirenal extravasation of the irrigation solution. Even with a wide-lumen ureteral catheter in place, drainage via the ureter is not sufficient to maintain the intrapelvic pressure in the physiologic range.


Repeatability, reproducibility and sequential use of condition scoring of Bos indicus cattle.
There is a scarcity in the literature of statistical analyses of condition score data. This paper assesses the repeatability and reproducibility of a condition scoring system in order to test whether it can be sufficiently reliable for widespread use and statistical treatment. Differences in cow condition resulting from an eight-month dry season, changes in lactational status and watering frequency were used to demonstrate how condition score data can be used sequentially in parallel with weight or heart girth data to monitor changes in body reserves over a prolonged period. The condition scoring system is based on a nine-point scale and its superiority over a six-point scale is demonstrated under the conditions encountered in Africa. An analysis of the trend in condition over time showed that cows watered daily lost condition linearly while cows watered every three days lost condition in a quadratic decline.


The control of tonic tension by membrane potential and intracellular sodium activity in the sheep cardiac Purkinje fibre.
Intracellular Na activity (aiNa) was measured with recessed-tip, Na-selective micro-electrodes in voltage-clamped sheep cardiac Purkinje fibres. Tension was measured simultaneously. aiNa was increased reversibly either by exposing the preparation to K-free, Rb-free solution of by adding the cardioactive steroid strophanthidin. An increase of aiNa produced an increase of tonic tension which was larger at depolarized membrane potentials. At sufficiently negative membrane potentials, changes of aiNa (over the range 6-30 mM) had no effect on tonic tension. Therefore, both an increase of aiNa and a depolarization are required to increase tonic tension. It is concluded that either a low level of aiNa or a large negative membrane potential is sufficient to maintain a low intracellular Ca concentration. Tonic tension was measured as a function of aiNa. At a given membrane potential the relationship can be described empirically by an equation of the form: tonic tension = b(aiNa)y, where y is a constant and b depends on membrane potential. In five experiments y was found to be 3.7 +/- 0.7 (mean +/- S.E.M.) over a range of potentials from -60 to -10 mV. Tonic tension was measured as a function of membrane potential. At a given aiNa the relationship can be described approximately as: tonic tension = k exp (aV), where a is a constant and k depends on aiNa. In five experiments a was found to be 0.06 +/- 0.01 mV-1 (mean +/- S.E.M.). A depolarization of 10 mV increases tonic tension by the same amount as does an increase of aiNa that is equivalent to a 3.7 mV change of the Na equilibrium potential, ENa. Hence ENa is nearly 3 times more effective than membrane potential in controlling tonic tension. During a prolonged depolarization (several minutes) the initial increase of tonic tension decays gradually. This is associated with a fall of aiNa. The relationship between tonic tension and aiNa is similar to that seen when aiNa is increased by inhibiting the Na pump. It is concluded that the fall of aiNa is responsible for the decay of tonic tension. The changes of tonic tension reported in this paper are consistent with the effects of aiNa and membrane potential on a voltage-dependent Na-Ca exchange. The possibility that a voltage-dependent Ca channel contributes to tonic tension is also discussed.


Impact of a single bout of resistance exercise on serum Klotho in healthy young men.
It has been shown that Klotho protects vascular endothelial function. Given that a single bout of resistance-exercise-induced hypertensive stimulus causes endothelial dysfunction, we postulated that acute resistance exercise would reduce serum Klotho levels. In this respect, the reduction in serum Klotho levels would be associated with the response of flow-mediated dilation (FMD). Therefore, the purpose of this study was to investigate the impact of acute resistance exercise on the Klotho response in serum. In addition, we examined the relationship between the serum Klotho and FMD responses following acute resistance exercise. Twelve untrained men participated in this study (20.4 ± 0.3 years). Following baseline measurements (blood pressure, blood collection, FMD), subjects performed leg extensions, which consisted of 10 repetitions for five sets at 70% of one-repetition maximum. After the exercise, measurement of blood pressure, blood collection, and FMD assessment were repeated for 60 min. We analyzed Klotho and endothelin-1 (ET-1) concentrations in blood serum. As expected, the exercise significantly elevated blood pressure and led to decreased FMD (p < 0.05). However, Klotho concentrations were significantly increased following exercise (p < 0.05). No correlation was observed in Klotho and FMD responses following acute resistance exercise. However, there was a significant positive correlation between Klotho and ET-1 in response to resistance exercise (p < 0.05). In conclusion, the present study reveals that serum Klotho significantly increased following a single bout of resistance exercise. However, the increase in Klotho may not associate with the acute reduction in endothelial function.


Actions of endothelin-1 on prostaglandin production by gestational tissues.
Endothelin-1 (10(-11)M-10(-7)M) was incubated with human umbilical vein endothelial cells and cells derived from amnion and decidua and prostaglandin production was determined. The rates of biosynthesis of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and prostaglandin E2 (PGE2) by endothelial cells were increased significantly by treatment with endothelin-1. Amnion cell PGE2 production was reduced significantly by endothelin-1 treatment whereas decidual PGE2 and prostaglandin F2 alpha production was unaffected by this treatment. Thus, it is possible that endothelins may play a part in the regulation of uteroplacental hemodynamics and the mechanisms of parturition.


Theranostics applications of quantum dots in regenerative medicine, cancer medicine, and infectious diseases.
Quantum dots (QDs) have attracted attention for their application and commercialization in all industrial fields, including communications, displays, and solar cells, due to their excellent optical properties based on the quantum size effect. In recent years, the development of QDs that do not contain cadmium which is toxic to cells and living organisms, has progressed, and they have attracted considerable attention in the bio-imaging field for targeting molecules and cells. Furthermore, recently, the need for diagnostics and treatment at the single molecule and single cell level in the medical field has been increasing, and the application of QDs in the medical field is also accelerating. Therefore, this paper outlines the frontiers of diagnostic and therapeutic applications (theranostics) of QDs, especially in advanced medical fields such as regenerative medicine, oncology, and infectious diseases.


Genetic transferrin types and iron-binding: a comparative study of a European and an African population sample.
Two population samples, one from Europe and one from Africa, were analyzed for the distribution of genetic transferrin (TF) types, serum concentrations of TF, serum iron concentrations and free iron-binding capacities. In Europeans the distribution of the TF alleles was C1 = 0.816, C2 = 0.143, C3 = 0.037, and B2 = 0.004. In black Africans the allele frequencies were: C1, 0.823; C2, 0.104; and D1 = 0.073; TFC3 was absent. The mean serum concentrations were 362 +/- 88 mg/dl in Europeans and 528 +/- 176 mg/dl in Africans; this difference was statistically significant. The concentration of serum immunoglobulins was also elevated in black Africans although their health was reported to be normal. The serum iron concentrations in Africans were decreased; the free iron-binding capacity of TF was, thus, increased. In both population samples there was a tendency for slightly higher TF concentrations in the TF C1 subtype than the TF C2 subtype. This correlation was not statistically significant. Analysis of a larger sample is required to establish this relationship.


Magnetic resonance myocardial T1ρ mapping : Technical overview, challenges, emerging developments, and clinical applications.
The potential of cardiac magnetic resonance to improve cardiovascular care and patient management is considerable. Myocardial T1-rho (T1ρ) mapping, in particular, has emerged as a promising biomarker for quantifying myocardial injuries without exogenous contrast agents. Its potential as a contrast-agent-free ("needle-free") and cost-effective diagnostic marker promises high impact both in terms of clinical outcomes and patient comfort. However, myocardial T1ρ mapping is still at a nascent stage of development and the evidence supporting its diagnostic performance and clinical effectiveness is scant, though likely to change with technological improvements. The present review aims at providing a primer on the essentials of myocardial T1ρ mapping, and to describe the current range of clinical applications of the technique to detect and quantify myocardial injuries. We also delineate the important limitations and challenges for clinical deployment, including the urgent need for standardization, the evaluation of bias, and the critical importance of clinical testing. We conclude by outlining technical developments to be expected in the future. If needle-free myocardial T1ρ mapping is shown to improve patient diagnosis and prognosis, and can be effectively integrated in cardiovascular practice, it will fulfill its potential as an essential component of a cardiac magnetic resonance examination.


Diagnosing Alzheimer's Disease from Circulating Blood Leukocytes Using a Fluorescent Amyloid Probe.
Toxic amyloid-β (Aβ) peptides aggregate into higher molecular weight assemblies and accumulate not only in the extracellular space, but also in the walls of blood vessels in the brain, increasing their permeability, and promoting immune cell migration and activation. Given the prominent role of the immune system, phagocytic blood cells may contact pathological brain materials. To develop a novel method for early Alzheimer's disease (AD) detection, we used blood leukocytes, that could act as "sentinels" after trafficking through the brain microvasculature, to detect pathological amyloid by labelling with a conformationally-sensitive fluorescent amyloid probe and imaging with confocal spectral microscopy. Formalin-fixed peripheral blood mononuclear cells (PBMCs) from cognitively healthy control (HC) subjects, mild cognitive impairment (MCI) and AD patients were stained with the fluorescent amyloid probe K114, and imaged. Results were validated against cerebrospinal fluid (CSF) biomarkers and clinical diagnosis. K114-labeled leukocytes exhibited distinctive fluorescent spectral signatures in MCI/AD subjects. Comparing subjects with single CSF biomarker-positive AD/MCI to negative controls, our technique yielded modest AUCs, which improved to the 0.90 range when only MCI subjects were included in order to measure performance in an early disease state. Combining CSF Aβ42 and t-Tau metrics further improved the AUC to 0.93. Our method holds promise for sensitive detection of AD-related protein misfolding in circulating leukocytes, particularly in the early stages of disease.


Transfer of the flexor carpi ulnaris to the radial wrist extensors in cerebral palsy.
Fourteen patients with cerebral palsy who had had transfer of the flexor carpi ulnaris (FCU) to the extensor carpi radialis longus (ECRL) and/or extensor carpi radialis brevis (ECRB) were examined. Two questions were posed: (1) What was the postoperative arc of active wrist motion? and (2) Did the procedure improve the grasp and release mechanism in hand function? The procedure was successful in the majority of patients; wrist arc of motion was improved and grasp and release was enhanced after operation.


Immune response in influenza virus infection and modulation of immune injury by viral neuraminidase.
Influenza A viruses cause severe respiratory illnesses in humans and animals. Overreaction of the innate immune response to influenza virus infection results in hypercytokinemia, which is responsible for mortality and morbidity. The influenza A virus surface glycoprotein neuraminidase (NA) plays a vital role in viral attachment, entry, and virion release from infected cells. NA acts as a sialidase, which cleaves sialic acids from cell surface proteins and carbohydrate side chains on nascent virions. Here, we review progress in understanding the role of NA in modulating host immune response to influenza virus infection. We also discuss recent exciting findings targeting NA protein to interrupt influenza-induced immune injury.


Quantifying hydrological-ecological response relationships based on zooplankton index of biotic integrity and comprehensive habitat quality index - A case study of typical rivers in Xi'an, China.
With the accelerated development of urbanization, rivers in urban areas have become the most closely synergized water ecosystem between human activities and natural processes. To achieve the restoration goal of using hydrological regime change-ecological response relationship to advance the sustainable development of regulated river ecosystems, this study collected ecohydrological data at four tributaries of the Wei River system (Ba, Chan, Feng, and Hei Rivers) at a total of 24 stations in October 2020 and June 2021. Taking ecological flow as hydrological parameter and zooplankton as indicator organism, combined with habitat data scored on-site, the indicator system of zooplankton index of biological integrity and comprehensive habitat quality index was established to explore the hydrological-ecological response relationship in a multi-dimensional way. The results showed that during the ebb stage, the ecological health of the Feng River was better overall, with an average ecological flow value of 267.09 ± 348.62. The ecological health of the Hei River was the worst, with an average ecological flow value of 37.80 ± 38.80. During the abundant water period, the ecological health of the Chan River was optimal with an average ecological flow value of 189.25 ± 190.10, while the ecological health of the Hei River remained unimproved, but the average ecological flow value increased by 283.12 ± 197.76. There was a clear negative correlation relationship between the comprehensive habitat quality index and ecological flow. The correlation between zooplankton index of biological integrity and ecological flows is extremely strong and threshold values exist, but there is strong heterogeneity in the interaction of disturbance factors across water systems, which may not provide a predictable response to flow changes. This study aims to provide a case reference for flow management in watersheds that also lack long-time series hydrological data and to contribute new thinking to the wide application of the hydrological-ecological response relationship.


Combining neural network and genetic algorithm for prediction of lung sounds.
Recognition of lung sounds is an important goal in pulmonary medicine. In this work, we present a study for neural networks-genetic algorithm approach intended to aid in lung sound classification. Lung sound was captured from the chest wall of The subjects with different pulmonary diseases and also from the healthy subjects. Sound intervals with duration of 15-20 s were sampled from subjects. From each interval, full breath cycles were selected. Of each selected breath cycle, a 256-point Fourier Power Spectrum Density (PSD) was calculated. Total of 129 data values calculated by the spectral analysis are selected by genetic algorithm and applied to neural network. Multilayer perceptron (MLP) neural network employing backpropagation training algorithm was used to predict the presence or absence of adventitious sounds (wheeze and crackle). We used genetic algorithms to search for optimal structure and training parameters of neural network for a better predicting of lung sounds. This application resulted in designing of optimum network structure and, hence reducing the processing load and time.


Genetic analysis of the Bacillus licheniformis degSU operon and the impact of regulatory mutations on protease production.
Disruption experiments targeted at the Bacillus licheniformis degSU operon and GFP-reporter analysis provided evidence for promoter activity immediately upstream of degU. pMutin mediated concomitant introduction of the degU32 allele--known to cause hypersecretion in Bacillus subtilis-- resulted in a marked increase in protease activity. Application of 5-fluorouracil based counterselection through establishment of a phosphoribosyltransferase deficient Δupp strain eventually facilitated the marker-free introduction of degU32 leading to further protease enhancement achieving levels as for hypersecreting wild strains in which degU was overexpressed. Surprisingly, deletion of rapG--known to interfere with DegU DNA-binding in B. subtilis--did not enhance protease production neither in the wild type nor in the degU32 strain. The combination of degU32 and Δupp counterselection in the type strain is not only equally effective as in hypersecreting wild strains with respect to protease production but furthermore facilitates genetic strain improvement aiming at biological containment and effectiveness of biotechnological processes.


Bouts and breaks in children's sedentary time: currently used operational definitions and recommendations for future research.
Increasing attention is paid to the potential health effects of children's sedentary bouts and breaks, rather than total sedentary time. This paper discusses currently used operational definitions of sedentary bouts and breaks in studies among children. Remarkably, these studies applied different operational definitions, complicating comparison between studies. To advance the field of sedentary behaviour epidemiology, we need a clear and 'evidence-based' operationalization for such sedentary bouts and breaks.