Timing of Newborn Blood Collection Alters Metabolic Disease Screening Performance.
Blood collection for newborn genetic disease screening is preferably performed within 24-48 h after birth. We used population-level newborn screening (NBS) data to study early postnatal metabolic changes and whether timing of blood collection could impact screening performance. Newborns were grouped based on their reported age at blood collection (AaBC) into early (12-23 h), standard (24-48 h), and late (49-168 h) collection groups. Metabolic marker levels were compared between the groups using effect size analysis, which controlled for group size differences and influence from the clinical variables of birth weight and gestational age. Metabolite level differences identified between groups were correlated to NBS data from false-positive cases for inborn metabolic disorders including carnitine transport defect (CTD), isovaleric acidemia (IVA), methylmalonic acidemia (MMA), and phenylketonuria (PKU). Our results showed that 56% of the metabolites had AaBC-related differences, which included metabolites with either decreasing or increasing levels after birth. Compared to the standard group, the early-collection group had elevated marker levels for PKU (phenylalanine, Cohen's d = 0.55), IVA (C5, Cohen's d = 0.24), MMA (C3, Cohen's d = 0.23), and CTD (C0, Cohen's d = 0.23). These findings correlated with higher false-positive rates for PKU (P < 0.05), IVA (P < 0.05), and MMA (P < 0.001), and lower false-positive rate for CTD (P < 0.001) in the early-collection group. Blood collection before 24 h could affect screening performance for some metabolic disorders. We have developed web-based tools integrating AaBC and other variables for interpretive analysis of screening data.


Effect of surface acetylation of chitin nanocrystals on the preparation and viscoelasticity of sunflower seed oil-in-water Pickering emulsions.
Acetylated chitin nanocrystals (ChNCs) were used as stabilizer in this work to prepare sunflower seed oil-in-water emulsions for the morphological and rheological studies. The results revealed that the acetylation with moderate degree of substitution (0.38) reduced hydrophilicity and increased surface charge level of rod-like ChNCs, and as a result, significantly improved the emulsifying ability of ChNCs. At the same oil/water ratio and particle loading, the emulsions stabilized with the acetylated ChNCs had far smaller droplet size (∼3 μm) as compared to the emulsions stabilized with the pristine ChNCs (5-7 μm). The increased droplets numbers and improved surface coating level resulted in the enhanced viscous resistance and yield stress level, which improved the physical stability of the acetylated ChNC-stabilized emulsions as a result. In addition, the droplet clusters easily formed in this system, contributing to weak strain overshoot and decreased large-deformation sensitivity during dynamic shear flow. Therefore, the acetylated ChNC-stabilized system showed enhanced transient stress overshoot during startup flow and weakened thixotropy during cyclic ramp shear flow as compared to the pristine ChNC-stabilized system. The relationships between surface acetylation of ChNCs and flow behavior of emulsions were then established, which provide valuable information on the modulation of the ChNC-stabilized Pickering emulsions.


The Effects of Augmented Reality on Prelicensure Nursing Students' Anxiety Levels.
Prelicensure nursing students experience high anxiety as they enter the clinical setting, which can have a negative impact on learning care performance and critical thinking. This study explored the viability of an innovative technological teaching strategy, augmented reality (AR), as a platform to prepare students and decrease their anxiety levels when entering a new environment. A pretest/posttest quasiexperimental design was used to assess the effect of AR 360 photosphere on preli-censure nursing students' anxiety levels as they entered a new clinical environment compared with anxiety levels of prelicensure nursing students who participated in the traditional faculty-led orientation method. Students from three midwestern colleges of nursing completed the State-Trait Anxiety Inventory before and after completing the AR 360 photosphere orientation or a faculty-led orientation. An independent t test revealed no difference in students' anxiety levels between the two methods of orientation. Although there were no significant differences in nursing students' anxiety levels between the two methods of clinical orientation, the AR 360 can be a valuable method of orientation that saves faculty time and ensures more consistent and uniform content compared with the traditional faculty orientation method. [J Nurs Educ. 2020;59(3):142-148.].


Assessing sexual assault survivors' access to emergency contraception: results from a mixed methods study in South Carolina.
Provision of emergency contraceptive pills (ECPs) is widely recognized as the standard of care to prevent pregnancy after a sexual assault. However, previous research has shown that hospitals do not routinely counsel sexual assault patients about or provide sexual assault survivors with ECPs or accurate referrals. We undertook a mixed methods study to assess policies and practices regarding the provision of ECPs for sexual assault survivors in South Carolina. The study includes four components: An analysis of the South Carolina Victims' Rights Amendment, in-depth interviews with rape crisis agency and state agency representatives, a survey of hospital emergency department staff, and a survey of hospital emergency department administrators. Our findings indicate that hospital policies and practices regarding ECP-related services for sexual assault patients are generally consistent with the standard of care. According to hospital staff and administrators, requiring a police report and/or undergoing a rape kit examination before providing ECPs do not seem to be significant access barriers. However, hospitals that do not conduct rape kit examinations transfer patients to other facilities, and these initial hospitals do not routinely provide patients with ECPs before transfer. Our findings suggest that further research to document whether transfer practices and reporting requirements impede access to ECPs is warranted. Furthermore, our results support the recommendation that any woman reporting sexual assault should be immediately offered dedicated, progestin-only ECPs. Last, our results suggest that key stakeholders in the sexual assault community could be engaged to improve sexual assault and ECP-related services in South Carolina.


Essential roles of retinoic acid signaling in interdigital apoptosis and control of BMP-7 expression in mouse autopods.
We previously reported that mice lacking the RARgamma gene and one or both alleles of the RARbeta gene (i.e., RARbeta+/-/RARgamma-/- and RARbeta-/-/RARgamma-/- mutants) display a severe and fully penetrant interdigital webbing (soft tissue syndactyly), caused by the persistence of the fetal interdigital mesenchyme (Ghyselinck et al., 1997, Int. J. Dev. Biol. 41, 425-447). In the present study, these compound mutants were used to investigate the cellular and molecular mechanisms involved in retinoic acid (RA)-dependent formation of the interdigital necrotic zones (INZs). The mutant INZs show a marked decrease in the number of apoptotic cells accompanied by an increase of cell proliferation. This marked decrease was not paralleled by a reduction of the number of macrophages, indicating that the chemotactic cues which normally attract these cells into the INZs were not affected. The expression of a number of genes known to be involved in the establishment of the INZs, the patterning of the autopod, and/or the initiation of apoptosis was also unaffected. These genes included BMP-2, BMP-4, Msx-1, Msx-2, 5' members of Hox complexes, Bcl2, Bax, and p53. In contrast, the mutant INZs displayed a specific, graded, down-regulation of tissue transglutaminase (tTG) promoter activity and of stromelysin-3 expression upon the removal of one or both alleles of the RARbeta gene from the RARgamma null genetic background. As retinoic acid response elements are present in the promoter regions of both tTG and stromelysin-3 genes, we propose that RA might increase the amount of cell death in the INZs through a direct modulation of tTG expression and that it also contributes to the process of tissue remodeling, which accompanies cell death, through an up-regulation of stromelysin-3 expression in the INZs. Approximately 10% of the RARbeta-/- /RARgamma-/- mutants displayed a supernumerary preaxial digit on hindfeet, which is also a feature of the BMP-7 null phenotype (Dudley et al., 1995, Genes Dev. 9, 2795-2807; Luo et al., 1995, Genes Dev. 9, 2808-2820). BMP-7 was globally down-regulated at an early stage in the autopods of these RAR double null mutants, prior to the appearance of the digital rays. Therefore, RA may exert some of its effects on anteroposterior autopod patterning through controlling BMP-7 expression.


Promoting the efficiency and selectivity of NO3--to-NH3 reduction on Cu-O-Ti active sites via preferential glycol oxidation with holes.
The combined reductive and oxidative reaction is the essence of a solar-driven photoredox system. Unfortunately, most of these efforts focus on the specific half-reactions, and the key roles of complete photoredox reactions have been overlooked. Taking the nitrate reduction reaction (NO3-RR) as a typical multiple-electrons involved process, the selective reduction of the NO3- into ammonia (NH3) synthesis with high efficiency is still a grand challenge. Herein, a rational oxidative half-reaction is tailored to achieve the selective conversion of NO3- to NH3 on Cu-O-Ti active sites. Through the coupled NO3-RR with glycol oxidation reaction system, a superior NH3 photosynthesis rate of 16.04 ± 0.40 mmol gcat-1 h-1 with NO3- conversion ratio of 100% and almost 100% of NH3 selectivity is reached on Cu-O-Ti bimetallic oxide cluster-anchored TiO2 nanosheets (CuOx@TNS) catalyst. A combination of comprehensive in situ characterizations and theoretical calculations reveals the molecular mechanism of the synergistic interaction between NO3-RR and glycol oxidation pair on CuOx@TNS. The introduction of glycol accelerates the h+ consumption for the formation of alkoxy (•R) radicals to avoid the production of •OH radicals. The construction of Cu-O-Ti sites facilitates the preferential oxidation of glycol with h+ and enhances the production of e- to participate in NO3-RR. The efficiency and selectivity of NO3--to-NH3 synthesis are thus highly promoted on Cu-O-Ti active sites with the accelerated glycol oxidative half-reaction. This work upgrades the conventional half photocatalysis into a complete photoredox system, demonstrating the tremendous potential for the precise regulation of reaction pathway and product selectivity.


Roles of the Taql and Bsml vitamin D receptor gene polymorphisms in hospital mortality of burn patients.
The aim of this study was to evaluate the roles of the Taql and Bsml vitamin D receptor gene polymorphisms in hospital mortality of burn patients. In total, 105 consecutive burn injury patients over 18 years in age who were admitted to the Burn Unit of Bauru State Hospital from January to December 2013 were prospectively evaluated. Upon admission, patient demographic information was recorded and a blood sample was taken for biochemical analysis to identify the presence of the Taql(rs731236) and Bsml(rs1544410) polymorphisms. All of the patients were followed over their hospital stay and mortality was recorded. Eighteen of the patients did not sign the informed consent form, and there were technical problems with genotype analysis for 7 of the patients. Thus, 80 patients (mean age, 42.5±16.1 years) were included in the final analysis. In total, 60% of the patients were male, and 16.3% died during the hospital stay. The genotype frequencies for the Taql polymorphism were 51.25% TT, 41.25% TC and 7.50% CC; for the Bsml polymorphism, they were 51.25% GG, 42.50% GA and 6.25% AA. In logistic regression analysis, after adjustments for age, gender and total body surface burn area, there were no associations between the Taql (OR: 1.575; CI95%: 0.148-16.745; p=0.706) or Bsml (OR: 1.309; CI95%: 0.128-13.430; p=0.821) polymorphisms and mortality for the burn patients. Our results suggest that the Taql and Bsml vitamin D receptor gene polymorphisms are not associated with hospital mortality of burn patients.


Dynamic metabolic changes during the first 3 months after 90Y-ibritumomab tiuxetan radioimmunotherapy.
To elucidate the time course of tumor metabolism during the first 3 months after (90)Y-ibritumomab tiuxetan radioimmunotherapy (RIT) in patients with refractory malignant lymphoma. Seven patients with recurrent follicular lymphoma underwent FDG-PET imaging before and after 1-, 4-, and 12-week RIT with (90)Y-ibritumomab tiuxetan. Tumor metabolic activity on FDG-PET scans was assessed as the maximum standard uptake value (SUVmax). Decrease in metabolism was detected 1 week after RIT. In the most decreased lesion, SUVmax decreased to 20% of the baseline value during the first week. Most lesions continued to decrease for up to 4 weeks. Some lesions showed increased metabolism from 4 to 12 weeks, while the level of FDG accumulations at 12 weeks was still lower than the baseline. Tumor response to RIT could be observed as early as 1 week after the administration of RIT. After tumor activity decreases, the metabolism may increase at least between 4 and 12 weeks. It suggests that the metabolic changes should be carefully evaluated during this period.


[Cause analysis of spinal surgery in ankylosing spondylitis].
To investigate the common cause of spinal surgery in ankylosing spondylitis (AS) and to develop reasonable and effective treatment programs for rhematologists. In this study, 79 AS patients (72 males, 7 females) hospitalized in the Department of Orthopedic and received spinal surgery in Peking University Third Hospital from January 2007 to July 2013 were investigated retrospectively. The causes of the spinal surgery were analyzed. The majority of the surgery were of cervical vertebra surgery for 59 cases (74.7%), followed by the thoracolumbar vertebra, thoracic vertebra, cervicothoracic vertebra, and lumbar vertebra. The common causes of AS spinal surgery were instability (53.2%) including fracture and dislocation caused by trauma mostly, followed by compression symptoms (34.1%). However, the orthopaedic surgery (12.7%) was not the predominant surgery causes. The most common cause of cervical surgery was cervical spondylosis (25 cases), followed by cervical fracture (22 cases) and cervical dislocation (10 cases). For cervical fracture, the most common site was C7 (8 cases). Atlanto-axial vertebral lesions (13 cases) induced by dislocation, subluxation, instability and fracture were common in cervical vertebra surgery. The age and disease duration of atlantoaxial surgical patient's were less than other parts of the cervical surgery. Thoracolumbar vertebra surgery included thoracolumbar kyphosis orthopaedic surgery (10 cases), and fractures (6 cases), which mainly occurred in T11-12 vertebrae. According to the time of admission for surgery, the cases of AS that received spinal surgery were 34 from 2007 to 2008. The number of the cases that accepted the surgery decreased gradually year by year. The majority surgery section was cervical vertebra, and atlanto-axial vertebral lesions were not rare as we thought. The main etiology of spinal surgery for AS patients was instability, e.g. fracture and compression symptoms. Of course, trauma accounted for the relative percentage of this phetonomenon. Although, the annual number of patients who receives spinal surgery is decreasing, to go to make early diagnosis and treatment, and to standardize patient education for AS patients are still important.


AIM2/IL-1α/TGF-β Axis in PBMCs From Exacerbated Chronic Obstructive Pulmonary Disease (COPD) Patients Is Not Related to COX-2-Dependent Inflammatory Pathway.
Chronic obstructive pulmonary disease (COPD) is a lung disorder characterized by persistent respiratory symptoms and progressive airflow limitation as a consequence of a chronic inflammatory response. Corticosteroids are the main treatment for COPD patients with a history of exacerbation, in that they attenuate exacerbation and dyspnea, and improve the response to bronchodilators. Nevertheless, despite corticosteroid administration, COPD patients still undergo exacerbation phases. In this context, the aim of this study was to evaluate the activity of Absent in melanoma 2 (AIM2) inflammasome-dependent pathways under corticosteroid treatment during COPD exacerbation. Stable and exacerbated COPD-derived Peripheral Blood Mononuclear Cells (PBMCs) were treated with a well-known anti-inflammatory agent, Dexamethasone (DEX), in the presence or not of Poly (deoxyadenylic-deoxythymidylate) acid (Poly dA:dT), an AIM2 ligand. We found that IL-1α was highly increased when AIM2 was activated from Poly dA:dT in exacerbated, but not in stable, COPD-derived PBMCs. To note, the release of IL-1α after the stimulation of AIM2 in PBMCs obtained from stable (hospitalized) COPD patients was not higher from the basal conditions, though it was still as high as that observed for Poly dA:dT-stimulated PBMCs obtained from exacerbated patients. This effect was associated with a higher expression of AIM2 in pair-matched circulating CD14+ cells obtained from hospitalized patients who passed from the exacerbation to stable status. Because the difference between stable and exacerbated COPD patients relies on the treatment with corticosteroids, exacerbated and stable COPD-derived PBMCs were treated with DEX. Indeed, the release of IL-1α and TGF-β was not altered after DEX treatment. In conclusion, we found that the administration of DEX in vitro on exacerbated COPD-derived PBMCs was not able to revert the detrimental inflammatory mechanism associated with AIM2 activation responsible for the release of IL-1α and the ensuing TGF-β, contributing to the severity of disease.


Modulation of melanosome ultrastructure in cultured embryonic pigment cells.
Melanosomes synthesized by embryonic chick retinal pigment cells in vitro are of a different size and shape than those made in ovo and in vivo. Ultrastructurally, the melanosomes made by cultured cells are small, spherical, contain an irregular internal matrix, and appear similar to the pheomelanosomes found in red hair and feathers. This modulation in melanosome ultrastructure in cultured retinal pigment cells does not appear to be caused by an irreversible change in differentiated capability but to a response of cells to the culture environment. Cells grown in embryo extract-free and serum-free defined media were found to synthesize melanosomes of normal size and shape in vitro, although at a much reduced number. The predominant melanosome type found was still the smaller, spherical variety. It appears that some still unknown factors in the culture environment have produced a shift to a different type of melanogenesis.


Extended shift-rotation method for absolute interferometric testing of a spherical surface with pixel-level spatial resolution.
An improved shift-rotation method for the absolute testing of spherical surfaces is developed to obtain pixel-level spatial resolution and a low noise propagation ratio. The absolute testing process includes multiple rotational tests and two lateral shifting tests with large shifts. A wavefront reconstruction algorithm based on subaperture division and least squares fitting is proposed to reconstruct the surface figure of the test optics. Numerical simulation results show that the method reveals high-frequency figures missed in the traditional Zernike-based shift-rotation method. The algorithm error is lower than 0.4%, and the noise propagation ratio can be reduced by 70% using large shifts. The absolute testing of spherical optics is carried out to verify this method. One spherical surface was tested with the presented absolute testing method and the method using a point diffraction interferometer. The difference of the measurement results based on the two methods showed that the testing uncertainty reached 0.19 nm root mean square (RMS), which indicated that the presented method has potential subnanometer testing uncertainty.


Identifying health literacy and health system navigation needs among rural cancer patients: findings from the Rural Oncology Literacy Enhancement Study (ROLES).
Rural residence is associated with disparities in cancer-related outcomes. Guided by the Chronic Care Model (CCM), the Rural Oncology Literacy Enhancement Study (ROLES) assessed health literacy and patient navigation needs among rural cancer patients. A mixed methods (qualitative and quantitative) approach was used, including: in-depth interviews, health literacy assessments, and phone surveys with cancer patients (N = 53) from 5 oncology clinics in rural Wisconsin; focus groups and self-administered surveys with staff (N = 41) in these clinics. Within four dimensions of the CCM (community resources, self-management support, delivery system design, and decision support), this study uncovered multiple unmet navigation needs, health literacy limitations, and barriers to quality cancer care. System-level implementation of patient navigation and health literacy best practices could contribute to improved cancer care and patient outcomes among rural populations. Further research identifying effective interventions that reduce cancer disparities among rural cancer patients is necessary.


Interspecific and environment-induced variation in hypoxia tolerance in sunfish.
Hypoxia tolerance is a plastic trait, and can vary between species. We compared hypoxia tolerance (hypoxic loss of equilibrium, LOE, and critical O2 tension, Pcrit) and traits that dictate O2 transport and metabolism in pumpkinseed (Lepomis gibbosus), bluegill (L. macrochirus), and the naturally occurring hybrid in different acclimation environments (wild versus lab-acclimated fish) and at different temperatures. Wild fish generally had lower Pcrit and lower PO2 at LOE in progressive hypoxia than lab-acclimated fish, but time to LOE in sustained hypoxia (PO2 of 2kPa) did not vary between environments. Wild fish also had greater gill surface area and higher haematocrit, suggesting that increased O2 transport capacity underlies the environmental variation in Pcrit. Metabolic (lactate dehydrogenase, LDH; pyruvate kinase, PK; citrate synthase; cytochrome c oxidase) and antioxidant (catalase and superoxide dismutase) enzyme activities varied appreciably between environments. Wild fish had higher protein contents across tissues and higher activities of LDH in heart, PK in brain, and catalase in brain, liver, and skeletal muscle. Otherwise, wild fish had lower activities for most enzymes. Warming temperature from 15 to 25°C increased O2 consumption rate, Pcrit, PO2 at LOE, and haemoglobin-O2 affinity, and decreased time to LOE, but pumpkinseed had ≥2-fold longer time to LOE than bluegill and hybrids across this temperature range. This was associated with higher LDH activities in the heart and muscle, and lower or similar antioxidant enzyme activities in several tissues. However, the greater hypoxia tolerance of pumpkinseed collapsed at 28°C, demonstrating that the interactive effects of hypoxia and warming temperature can differ between species. Overall, distinct mechanisms appear to underpin interspecific and environment-induced variation in hypoxia tolerance in sunfish.


Randomized phase II study of gemcitabine and carboplatin +/- sequential docetaxel in non-small cell lung cancer.
Sequential administration of chemotherapeutic drugs might have advantages: additive toxicity is avoided and the individual drugs can be given in full dosages. The Swedish group earlier found the combination of gemcitabine and carboplatin to be effective and with acceptable toxicity. The group therefore decided to add docetaxel in a sequential way in a randomized phase II study. Patients were randomized to either gemcitabine or carboplatin for six cycles or the same regimen for three cycles followed by weekly single agent docetaxel. The primary objective was time to progression (TTP). One hundred and twenty-three patients with performance status WHO 0-2 and with earlier un-treated non-small cell lung cancer with measurable stage IIIB disease, not amenable to curative treatment, or stage IV disease without known metastatic spread to the CNS, were enrolled. Hematological toxicity was more common in the GC group but clinically significant bleeding or leucopenic fever occurred only in a minority of patients. No complete responses were noted. Partial response (PR) was observed in 19.3% and 20.8% in the GC and GCD group, respectively. Progression-free survival was 5.6 and 4.8 months and overall survival time 10.6 and 10.1 months in the GC and GCD groups, respectively. Thus, sequential treatment with docetaxel after treatment with gemcitabine and carboplatin did not improve time to progression, response rates, or overall survival.


Sexual dysfunction in the diabetic BB/WOR rat: a role of central neuropathy.
The pathophysiological mechanisms of diabetic impotence remain obscure. We have presented an analysis of sexual function in a diabetic rat (BB/WOR) model characterized by diffuse neuropathic changes without a confounding vasculopathy that allows us to define the neural components of erectile failure. Copulatory behavioral testing demonstrated that diabetic males were severely impaired: the controls mounted three times more than the diabetics and had about one-half the latency to first mount. The diabetics had about one-fourth the number of intromissions and took nearly twice as long to achieve first ejaculation. The number of ejaculations was drastically reduced as well. We examined sexual reflexes in the anesthetized acutely spinalized rat. These experiments tested the integrity of spinal circuits controlling sexual function. Reflex testing demonstrated that spinal sexual reflexes were also severely impaired: the onset latency of reflexes was more than doubled, and the duration of reflexes was less than one-half. More than one-half of the diabetic rats showed no penile erections. Neural studies showed even more derangement in reflex measures in rats, without erection. Nerve conduction velocity experiments suggested a peripheral neuropathic change in hypogastric nerve and motor pudendal nerve fibers. These dysfunctional findings were seen without any androgen deficiency. These results indicate that diabetic impotence in this model reflects central and peripheral neuropathic disease processes.


[Smoking and lung cancer].
Since fifty years it is clear now that smoking of tobacco products is responsible for the lung cancer epidemic that is currently in progress worldwide. Although in the Western world a small decrease of lung cancer in males is found, the number of female patients is steadily increasing. Changes in tobacco production have resulted in exposition of smokers to other carcinogens. This is probably the cause of the change in the histological pattern with an increase of adenocarcinoma and stabilisation of squamous cell lung cancer. Despite the bad prognosis there is some hope that with improvement of early detection methods more patients can be cured. However, for a real change it is necessary to discourage smoking by all means.


Anti-inflammatory activities of compounds from twigs of Morus alba.
Five new compounds, 10-oxomornigrol F (1), (7″R)-(-)-6-(7″-hydroxy-3″,8″-dimethyl-2″,8″-octadien-1″-yl)apigenin (2), ramumorin A (3), ramumorin B (4), and (4S,7S,8R)-trihydroxyoctadeca-5Z-enoic acid (5), together with 31 known compounds (6-36), were isolated from the twigs of Morus alba (Moraceae). The chemical structures of these compounds were established using spectroscopic analyses, 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and Mosher's methods. The anti-inflammatory activities of the compounds were evaluated by investigating their ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW 264.7 cells. Compounds 1, 2, 13, 17, 19, 25-28, and 32 showed inhibitory effects with IC50 values ranging from 2.2 to 5.3μg/mL. Compounds 1, 2, 17, 25, and 32 reduced LPS-induced inducible nitric oxide synthase (iNOS) expression in a concentration-dependent manner. In addition, pretreating the cells with compound 1, 17, and 32 significantly suppressed LPS-induced expression of cyclooxygenase-2 (COX-2) protein.


Quantitative predictions to conditions of zwitterionic stacking by transient moving chemical reaction boundary created with weak electrolyte buffers in capillary electrophoresis.
This paper develops a novel procedure of quantitative predictions for the on-column stacking conditions of a zwitterionic analyte by a moving chemical reaction boundary (MCRB) in capillary electrophoresis (CE). The procedure concerns the choice of the weak acidic running and alkaline sample buffers and the velocity design of MCRB created with the two buffers. Based on the theory of MCRB, the theoretical computations are performed. From the computations, the following two predictions are refined for the stacking conditions of zwitterion. (1) The zwitterion velocity in the acidic buffer should be greater than that of MCRB moving toward the cathode, or the zwitterion cannot be well stacked by the MCRB. (2) The gap between pH values of the acidic and alkaline sample buffers ought to comprise the isoelectric point (pI) of zwitterion to be stacked; namely, there exists the relation of pH (acidic buffer) < pI < pH (sample). The predictions are quantitatively proved by the experiments of zwitterionic stacking with two kinds of MCRBs. In addition, the experiments also show the tightly stacked peak of zwitterion existing in the process of MCRB, but not after the MCRB. The theoretical and experimental results hold obvious significances to other zwitterion (such as peptide and protein) on-column stacking in CE.


Metabolic profiling of Angelica acutiloba roots utilizing gas chromatography-time-of-flight-mass spectrometry for quality assessment based on cultivation area and cultivar via multivariate pattern recognition.
Gas chromatography time-of-flight mass spectrometry was applied to elucidate the profiling of primary metabolites and to evaluate the differences between quality differences in Angelica acutiloba (or Yamato-toki) roots through the utilization of multivariate pattern recognition-principal component analysis (PCA). Twenty-two metabolites consisting of sugars, amino and organic acids were identified. PCA analysis successfully discriminated the good, the moderate and the bad quality Yamato-toki roots in accordance to their cultivation areas. The results signified two reducing sugars, fructose and glucose being the most accumulated in the bad quality, whereas higher quantity of phosphoric acid, proline, malic acid and citric acid were found in the good and the moderate quality toki roots. PCA was also effective in discriminating samples derive from different cultivars. Yamato-toki roots with the moderate quality were compared by means of PCA, and the results illustrated good discrimination which was influenced most by malic acid. Overall, this study demonstrated that metabolomics technique is accurate and efficient in determining the quality differences in Yamato-toki roots, and has a potential to be a superior and suitable method to assess the quality of this medicinal plant.


Specific histologic and cytogenetic evidence for in vivo malignant transformation of murine host cells by three human prostate cancer cell lines.
The chromosomal constitutions of three murine cell lines that developed in vitro from tumors that grew in nude mice after orthotopic and ectopic injections of three human prostate tumor cell lines were examined by histopathology, conventional G-banding, and with fluorescence in situ hybridization techniques. All three murine cell lines showed unique marker chromosomes involving mouse chromosome 12, with a common break point. Histopathologic evidence from a murine prostate gland into which SP 3031 cells had been injected indicated dysplastic glandular epithelium and carcinomatous areas. These observations further indicate that: (a) human prostate tumors are capable of transforming host organ cells, (b) host cells have specific chromosomal alterations that may be associated with transformation, and (c) the process of host cell transformation can be demonstrated in histological sections. Although cancer cell heterogeneity and drug-resistant phenotypes are caused by additional genetic alterations and clonal evolution of the original tumor, transformation of the host's distant organ cells may also contribute because most therapies are directed only to the original cancer cells.


Runoff characteristics of highway pollutants based on a long-term survey through a year.
Highway pollutants generated mainly from traffics are repeating accumulation, raise, drift and move on the highways. Some of them are removed by road cleanings done regularly, the others are flushed by stormwater into receiving water. The objectives of this study are to survey characteristics of the highway pollutants, and to quantify their behavior on the highways. The study area is a part of Meishin Expressway running through the main island of Japan. Surveys on pollutant runoff from the highway were done for all storm events through one year from December 2004 to November 2005. For the surveys, samples were collected by continuous water sampling during storm events. And chemical substances in each sample such as SS, TOC, TN, TP, heavy metals and polycyclic aromatic hydrocarbons (PAHs) for each class of particle size were measured. Using the results of the survey, characteristics of pollutant runoff during storm events were examined. And it cleared the basic unit loads for the highway pollutants throughout a year. As a result, some significant knowledge for the environmental management of highway pollution has been obtained.


Global initiative for interdisciplinary approach to improve innovative clinical research and treatment outcomes in geriatrics: biological cell-based targeted drug delivery systems for geriatrics.
At the intersection of the late 20(th) century and early 21(st) century, a worldwide challenge began to emerge--how can the quality of life be improved for a steadily increasing elderly population. It is well known that elderly patients show increased susceptibility to infections and a higher incidence of co-morbidity rates. Older adults frequently demonstrate pharmacokinetic and pharmacodynamic changes promoting adverse drug reactions and complications. Analysis of world literature and practical observations indicate that new approaches are required in gerontology and geriatric medicine due to recent significant advances in biomedical science. Global interdisciplinary approaches to improve medical science and medical care services for growing elderly population are indicated. This global, interdisciplinary initiative should integrate select, tangible clinical results achieved in leading research centers and universities that are applicable in the field of geriatrics and helpful to geriatricians. Among past scientific and clinically significant study results in the field of biomedicine, one must consider targeted drug delivery systems (DDS), which are designed to minimize drug side effects, increase the efficacy of drugs, and prolong and target drug interactions with particular pathological foci in sick patients. Many review articles focus on various methods of drug encapsulation and pharmacokinetics, but not on developing clinical modalities. This article attempts to further the discussion with researchers and clinicians from various fields, as well as to encourage comprehensive and elderly patient-oriented research focused on clinical implementation of DDS, especially erythrocyte-based DDS.


Student nurses' perceptions of their educational environment at a school of nursing in Western Cape province, South Africa: A cross-sectional study.
Educational environments have been found to bear a substantial relationship with the academic performance and success, as well as the retention, of students. The study objectives were to (1) evaluate the educational environment as perceived by undergraduate nursing students at a school of nursing (SON) in Western Cape province and (2) investigate whether the educational environment, or components thereof, is perceived negatively or positively among undergraduate nursing students of different year level, gender, home language and ethnicity. A quantitative research method with a cross-sectional design was implemented. Data were collected from 232 undergraduate nursing students from a SON at a university in Western Cape province, South Africa. The subscales and the items of the educational environment questionnaire were compared among undergraduate nursing students. Data were analysed by means of the IBM Statistical Package for Social Sciences (IBM SPSS-24) using analysis of variances (ANOVAs), independent-sample t-tests, mean scores, standard deviations and percentages. The mean score attained for the entire participant group was 195 (standard deviation [SD] = 24.2) out of 268 (equivalent to 72.8% of maximum score), which indicated that the educational environment was perceived substantially more positively than negatively. The overall mean score was significantly higher (p < 0.05) for male students (M = 202; SD = 21) and for black students (M = 202; SD = 21). The digital resources (DR) subscale was the only subscale with a statement or item that was rated as absolute negative (M = 1.9; SD = 0.9). The educational environment at the institution concerned was perceived as predominantly positive by its undergraduate nursing students. Although the educational environment was predominantly perceived as positive, the results of this study also indicated that enhancements are required to improve the physical classroom conditions, skills laboratories, DR and the implemented teaching and learning strategies. It is vital for university management to prioritise the creation of an educational environment which would ensure that quality learning takes place.


Excitons in CsPbBr3 Halide Perovskite.
Excitons in Bridgman grown halide perovskite CsPbBr3 single crystals were examined using photoluminescence (PL) spectroscopy to determine the nature of the electronic states. The photoluminescence intensity was strongly temperature-dependent and depended upon the specific exciton band. At low temperatures intrinsic disorder and its related shallow below bandgap tail states determine the emission properties. Photoluminescence at low temperature revealed the presence of several strong bands at the band edge that is attributed to free or trapped/bound excitons. This PL emission results from strong electron-phonon coupling with an average phonon energy Eph of 6.5 and 27.4 meV for the emissions, comparable to that observed in other perovskites. The Huang-Rhys parameter S was calculated to be 3.81 and 1.51, indicating strong electron-phonon coupling. The interactions between electrons and phonons produce small polarons that tend to bind charge carriers and result in trapped/bound excitons. The transient photoluminescence response of each specific band was studied, and the results indicated a multiphonon recombination process. Average PL lifetimes of ∼17 ns for free excitons and ∼38 ns for trapped/bound excitons were determined. The observed edge states could be associated with native defects such as vacancies and interstitials, as well as twinning due to the cubic-to-tetragonal phase transition in CsPbBr3. Elimination of the trapping sites for binding excitons could lead to improved charge transport mobilities, carrier lifetimes, and detector properties in this system.


The Added-on of Ziziphus jujube Syrup in the Treatment of Chronic Spontaneous Urticaria Resistant to Standard-Dose of Secondary-generation H1 Antihistamine: A Double-Blind Randomized Clinical Trial.
Although antihistamines are the first-line treatment for chronic spontaneous urticaria (CSU), 50% of patients don't respond to standard doses. In this study, the effectiveness of Ziziphus jujube fruit syrup in combination with antihistamines was assessed in patients with CSU. This double-blind randomized clinical trial was conducted in Shiraz between December 2019 and December 2020. 64 patients with CSU who had experienced hives for at least six weeks and did not respond to the usual treatments were enrolled in the study. They were randomly assigned to intervention and control groups using permuted block random allocation. For four weeks, the intervention group received 7.5 mL Ziziphus jujube syrup twice a day, while the control group received 7.5 mL simple jujube syrup twice a day. Both groups received cetirizine 10 mg every night. Urticaria activity score (UAS) and CU-Q2oL questionnaires were used to assess urticaria state and sleep quality before and after each week for four consecutive weeks. Data were analyzed using SPSS software version 18, and P<0.05 was considered statistically significant. Before the intervention, there was no statistically significant difference between the two groups' mean of UAS (P=0.490) and sleep quality (P=0.423). During the follow-up, UAS in the intervention group was significantly lower (P=0.001). Moreover, this difference was significant on the day 28 (P=0.046). During the follow-up, the quality of sleep in both groups improved significantly, and this improvement was more significant in the intervention group. Ziziphus jujube syrup could be an effective adjuvant treatment for CSU.Trial Registration Number: IRCT20190304042916N1.


Occult tethered cord syndrome: a survey of practice patterns.
Tethered cord syndrome (TCS) is associated with a number of congenital anomalies involving early development of the spinal cord. These include myelomeningocele, spinal cord lipoma, low-lying conus medullaris, and a fibrofatty terminal filum. Occult TCS occurs in patients when clinical features indicate a TCS but the typical anatomical abnormalities are lacking. It is controversial whether surgical release of the terminal filum leads to clinical improvement in a patient who does not have a previously identified anatomical abnormality. To assess the clinical standard used by practicing pediatric neurosurgeons, a practice survey was conducted at the 2004 Annual Meeting of the Joint Section for Pediatric Neurological Surgery of the American Association of Neurological Surgeons/Congress of Neurological Surgeons. The survey examined clinical decision making for a same-case scenario with differing appearance on imaging studies. There was a clear consensus regarding diagnosis and treatment in the patient with symptoms, a low-lying conus medullaris, and a fatty terminal filum. The vast majority of respondents (85%) favored surgical untethering for this patient. A majority of respondents (67%) also favored treatment for the patient having symptoms and a fatty terminal filum. There was, however, significant disagreement regarding the diagnosis and treatment of disease in one patient with symptoms and an inconclusive magnetic resonance imaging study. Some respondents clearly favored surgery, whereas others believed that this patient did not meet the diagnostic criteria for TCS. The results of this survey support the development of a randomized clinical trial to address the benefit of surgery for occult TCS.


Molecular defects in Krabbe disease.
Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive neurodegenerative disorder that affects both the central and peripheral nervous systems due to an enzymatic defect of the galactocerebrosidase. In this study, molecular defects in Krabbe disease were investigated in 11 patients (seven Japanese and four non-Japanese) using cultured skin fibroblasts. A Japanese late infantile patient had a missense mutation of Pro at codon 302 to Ala and a non-Japanese patient had a missense mutation of Val at codon 550 to Gly. The reduced enzymatic activities expressed from the cDNAs with these missense mutations and from the previously reported nonsense mutation (E369X, Glu at codon 369 to stop codon) were confirmed. Genomic DNA analyses revealed that the P302A and E369X mutations were heterozygous and the V550G mutation was homozygous in these patients. A 12 base deletion with a 3 base insertion was found in three unrelated Japanese infantile patients, but not in 30 controls. The mutation was homozygous in two patients and heterozygous in one patient. We could not find any confirmed mutation in the coding region in the other six patients. These findings suggest that mutations in infantile and late infantile patients are relatively heterogeneous.


[Toxoplasmosis in the African tropical zone. Preliminary studies].
Toxoplasmosis in Tropical African area was not subject to many publications but the results indicate that toxoplasmosis may influence the health of the populations. We present prevalence studies carried out in the Central African Republic, Mali, Niger, Burkina-Faso, Togo to find toxoplasma-antibodies by Agglutination of Latex. For adults the lower percentage was found in the North Central African Republic villages (40%) and the higher in Mali (nearly 70%). These high percentages justify a larger epidemiological study in Tropical Africa.


Positive affect and pain: mediators of the within-day relation linking sleep quality to activity interference in fibromyalgia.
Fibromyalgia (FM) is a chronic pain condition often resulting in functional impairments. Nonrestorative sleep is a prominent symptom of FM that is related to disability, but the day-to-day mechanisms relating the prior night's sleep quality to next-day reports of disability have not been examined. This study examined the within-day relations among early-morning reports of sleep quality last night, late-morning reports of pain and positive and negative affect, and end-of-day reports of activity interference. Specifically, we tested whether pain, positive affect, and negative affect mediated the association between sleep quality and subsequent activity interference. Data were drawn from electronic diary reports collected from 220 patients with FM for 21 consecutive days. The direct and mediated effects at the within-person level were estimated with multilevel structural equation modeling. Results showed that pain and positive affect mediated the relation between sleep quality and activity interference. Early-morning reports of poor sleep quality last night predicted elevated levels of pain and lower levels of positive affect at late-morning, which, in turn, predicted elevated end-of-day activity interference. Of note, positive affect was a stronger mediator than pain and negative affect was not a significant mediator. In summary, the findings identify 2 parallel mechanisms, pain and positive affect, through which the prior night's sleep quality predicts disability the next day in patients with FM. Furthermore, results highlight the potential utility of boosting positive affect after a poor night's sleep as one means of preserving daily function in FM.


LATS1/YAP1 Axis Controls Bone Regeneration on Distraction Osteogenesis by Activating Wnt/β-catenin.
The Hippo signaling pathway inhibits cell growth, and its components and functions are highly conserved in mammals. LATS1 is a core component of the Hippo signaling pathway associated with lymphatic invasion, astrogliosis, apoptosis, and autophagy. Nevertheless, the role of Hippo/LATS1 in osteogenesis remains unclear. Here, we used ribonucleic acid (RNA) lentiviruses to inhibit the expression of Lats1 in bone marrow-derived stem cells (BMSCs) and distraction osteogenic regions in rats. Increased osteogenic, proliferative, and migratory abilities of BMSCs were observed in Lats1-inhibited BMSCs, while these phenotypes were partially reversed by YAP1 inhibition. In vivo, we found that the LATS1/YAP1 axis promoted osteogenesis during distraction osteogenesis (DO). β-catenin was positively correlated with YAP1 expression in vivo and in vitro. When YAP1 was strongly positive in the nucleus, β-catenin expression was upregulated; when YAP1 expression was inhibited by verteporfin, β-catenin was not expressed in the nucleus. These findings suggest that the LATS1/YAP1 signaling axis promotes DO by activating the Wnt/β-catenin signaling pathway. This study provides insights into osteogenesis's molecular mechanism and a potential therapeutic strategy for bone regeneration in DO by associating with LATS1/YAP1-β-catenin.


Effectiveness of serological markers of eosinophil activity in monitoring eosinophilic esophagitis.
it is necessary to find serological markers accessible in clinical practice to prevent the need to perform repeated endoscopies. to assess the efficacy of eosinophil activity markers in monitoring eosinophilic esophagitis (EoE). thirty patients were included prospectively, all under dietary treatment -diets excluding 6 foods, and allergy test based diet (skin prick test and specific IgE). The variables assessed were demographic parameters, eosinophil cationic protein (ECP) levels (μg/mL), total IgE (KU/L), peripheral blood eosinophils (PBE) (U/mm³), and the maximum peak of eosinophils/hpf in esophageal biopsies. The variation found between these figures was assessed in line with response to dietary treatment. thirty patients (66.7% males; mean age 33.43 years) were included in the study, 22 responders and 8 non-responders. Ninety percent presented a personal history of atopy. No significant decrease was detected in serum total IgE and ECP after diet in responder and nonresponders. However, the PBE decreased significantly in responders but not in nonresponders, PBE in responders (pre-diet. 397.27 vs. post-diet 276.81, p = 0.024) and non-responders PBE (pre-diet. 460 vs. post-diet 317.5, p = 0.23). serum total IgE and ECP do not act as markers for EoE activity. However PBE may play a role in this regard, bearing in mind that this parameter may be influenced by concomitant atopic conditions.


Climbing to reach females: Romeo should be small.
The race for reaching mates by the time they are receptive, or sexual selection by scramble competition, has received little attention. We argue that smaller males are favored in species in which the male must climb to reach females located in high habitat patches. This new explanation we term the "gravity hypothesis" of sexual size dimorphism (SSD). We show that a simple biomechanical model of animal movement predicts that: (1) selection should favor a comparatively smaller size in the searching sex when searching involves climbing; and (2) this effect should be stronger in larger species than in smaller species. In reaching high habitats, smaller, faster searchers will be favored either through sexual selection by scramble competition and/or by escaping predation easier by running faster on vertical surfaces. Different spider species are found at a wide range of heights. We compiled a dataset of spider taxa and arranged their habitats according to four height categories, ranked from soil surface to trees. We show that, after controlling for phylogeny, both predictions of the gravity hypothesis of SSD are met. Thus, it appears that the constraint imposed by gravity on climbing males is a selective factor in determining male dwarfism.


Critical Questions Regarding Gadolinium Deposition in the Brain and Body After Injections of the Gadolinium-Based Contrast Agents, Safety, and Clinical Recommendations in Consideration of the EMA's Pharmacovigilance and Risk Assessment Committee Recommendation for Suspension of the Marketing Authorizations for 4 Linear Agents.
For magnetic resonance, the established class of intravenous contrast media is the gadolinium-based contrast agents. In the 3 decades since initial approval, these have proven in general to be very safe for human administration. However, in 2006, a devastating late adverse reaction to administration of the less stable gadolinium-based contrast agents was identified, nephrogenic systemic fibrosis. The result of actions taken by the European Medicines Agency and the US Food and Drug Administration, stratifying the agents by risk and contraindicating specific agents in severe renal dysfunction, has led to no new cases being identified in North America or Europe. Subsequently, in 2014, long-term deposition in the brain of gadolinium was first shown, after administration of 2 nonionic linear chelates, gadodiamide, and gadopentetate dimeglumine. This has led to an intense focus on the question of in vivo distribution, possible dechelation, and subsequent deposition of gadolinium, together with substantial clarification of the phenomenon as well as stratification of the agents on this basis. This review focuses on 8 critical questions regarding gadolinium deposition in the brain and body, with the answers and discussion therein important for future regulatory decisions and clinical practice. It is now clear that dechelation of gadolinium occurs in vivo with the linear agents and is responsible for this phenomenon, with key experts in the field recommending, except where there is no suitable alternative, a shift in clinical practice from the linear to macrocyclic agents. In addition, on March 10, 2017, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency recommended suspension of the marketing authorization for 4 linear gadolinium contrast agents-specifically Omniscan, Optimark, Magnevist, and MultiHance (gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadobenate dimeglumine)-for intravenous injection. Cited in the report was convincing evidence of gadolinium deposition in the brain months after injection of these linear agents. Primovist/Eovist (gadoxetic acid disodium) will remain available, being used at a lower dose for liver imaging, because it meets an important diagnostic need. In addition, a formulation of Magnevist for intra-articular injection will remain available because of its very low gadolinium concentration.


Regulation of keratinocyte proliferation and differentiation by all-trans-retinoic acid, 9-cis-retinoic acid and 1,25-dihydroxy vitamin D3.
We studied the effect of all-trans retinoic acid (all-trans-RA), 9-cis-retinoic acid (9-cis-RA) and 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) on proliferation and differentiation of human keratinocytes cultured in a submerged culture system for up to 5 weeks and evaluated changes in cell morphology and in the expression of proliferation- and terminal differentiation-related genes on both the mRNA and the protein levels. Under control culture conditions, the expression of small proline-rich proteins (SPRR1 and SPRR2), involucrin, Ki67 and c-jun reached a maximum after 2 weeks in culture (1 week postconfluence) and then decreased as the tissue architecture of the cultures deteriorated. Upon simultaneous treatment with both retinoids and 1,25(OH)2D3 a culture was generated that remained stable for 4 weeks with at least eight living cell layers. Furthermore, this culture showed a pattern of SPRR2 and involucrin expression which closely resembled that of native epidermis, a maintained Ki67 expression and a strongly induced c-jun expression. Treatment with 1,25(OH)2D3 alone inhibited cell proliferation and stimulated cell differentiation resulting in acceleration of the differentiated phenotype and was accompanied by inhibition of c-jun and Ki67 expression and also, surprisingly by inhibition of SPRR1, SPRR2 and involucrin expression. In contrast, treatment with all-trans-RA and/or 9-cis-RA induced a more proliferative phenotype with a prolonged lifespan as compared to control cultures. SPRR1 was weakly repressed, SPRR2 was strongly repressed, a delayed induction of involucrin occurred, and c-jun and Ki67 expression were maintained. These results show that modulation of the composition of the medium by the addition of various vitamins results in changes in the balance between keratinocyte proliferation and differentiation which correspond to changes in the expression of proliferation and differentiation markers and prolongation of the culture lifespan.


[Analysis of the spatial-temporal EEG organization as the way to the knowledge of neurophysiological mechanisms of the integrative brain activity].
Short results' review of investigations of Laboratory of Neurophysiology of Child of Sechenov Institute is presented in the article. Investigations are based on concept of academic M.N. Livanov about special role of spatial-temporal relations of brain potentials oscillations of various brain areas in providing of functional connection between them. It is shown, that in rest condition the structure of interregional relations of cortex biopotentials in all healthy people is characterized by high spatial orderliness that obviously assists to optimal realization of informational processes during various functional conditions from rest to complex cognitive functions. Special attention is given for the problem of functional signigicance of phase shifts of EEG waves. Data, that allows concluding that brainstem and thalamocartical integrative systems are characterized with relatively small inherited and phenotypic variability whereas fiber systems of both hemispheres that provide processes of intercortical integration are characterized by more expressed inter-individual variability, is presented. Intensive development of long associative and commissural tracks of telencephalon that joined even the most distanced cortical regions of hemispheres in united formation apparently results in formation of morpho-functional "skeleton" of neocortex, that occurred to be the basis for origin of qualitatively new (in comparison to animals) principals of formation of system organization of integral activity of the brain. Existence of long mono- and oligo-synaptic connections provides conditions for correlative develoment in ontogenesis of new function that is not conditioned by phylogenetic development.


Return-to-Sport Time and Postoperative Performance in MLB Players Undergoing Wrist Arthroscopy.
Wrist injuries are common in sports and can result in prolonged time missed from playing. This study aimed to determine in Major League Baseball-players after arthroscopic wrist surgery the return-to-sport (RTS) rate, postoperative career length, and changes in performance compared with preoperative statistics and matched controls. Major League Baseball players who underwent arthroscopic wrist surgery from 1990 to 2019 were identified. Demographic and performance data were collected for each player, and matched controls were identified. Comparisons were made via paired samples Student t tests. Twenty-six players (27 surgeries) were identified. The average age of included players was 28.9 ± 2.9 years with an average professional experience of 5.2 ± 3.4 years. Eighty-four percent of players returned to sport, with an average RTS time of 5.0 ± 2.7 months. A statistically significant (P < .05) decrease was seen in preoperative and postoperative runs scored per season (95.6 ± 91.3 vs 41.0 ± 29.5), batting average (BA) (0.270 ± 0.024 vs 0.240 ± 0.036), and average wins above replacement (WAR) (1.5 ± 1.1 vs 0.8 ± 0.9). Major League Baseball players who underwent arthroscopic wrist surgery had an RTS rate of 84% at a mean time of 5.0 months. There was no significant difference in performance statistics between cases postoperatively and matched controls overall, with some differences in performance found when categorized by position. However, a significant decrease in performance among case players was observed between preoperative and postoperative performance, including runs per season, BA, and WAR.


The role of pH on the resistance of resting- and active anammox bacteria to NO2- inhibition.
The anaerobic oxidation of ammonium (anammox) uses nitrite as terminal electron acceptor. The nitrite can cause inhibition to the bacteria that catalyze the anammox reaction. The literature shows a great divergence on the levels of NO2 (-) causing inhibition. Moreover, the conditions influencing the resistance of anammox bacteria to NO2 (-) inhibitory effect are not well understood. This work investigated the effect of the pH and the concentration of nitrite on the activity and metabolism of anammox granular sludge under different physiological conditions. Batch activity tests in a range of pH values were carried out in which either actively metabolizing cells or resting cells were exposed to nitrite in the presence or absence of the electron donating substrate ammonium, respectively. The response of the bacteria was evaluated by analyzing the specific anammox activity, the accumulation of nitric oxide, and the evolution of the ATP content in the biomass. Additionally, the effect of the pH on the tolerance of the biomass to single substrate feeding interruptions was evaluated in continuous anammox bioreactors. The results show that the influence of the pH on the NO2 (-) inhibition of anammox bacteria is greater under non-metabolizing conditions than during active metabolism. The exposure of resting cells to NO2 (-) (100 mg N L(-1) ) at pH values below 7.2 caused complete inhibition of the anammox activity. The inhibition was accompanied by accumulation of the intermediate, nitric oxide, in the gas phase. In contrast, just mild inhibition was observed for resting cells exposed to the same NO2 (-) concentration at pH values higher than 7.5 or any of the pH values tested in assays with actively metabolizing cells. ATP initially increased and subsequently decreased in time after resting cells were exposed to NO2 (-) suggesting an active response of the cells to nitrite stress. Furthermore, bioreactors operated at pH lower than 6.8 had greater sensitivity to NO2 (-) during an ammonium feed interruption than a bioreactor operated at pH 7.1. The results suggest that the ability of resting cells to tolerate NO2 (-) inhibition is seriously impeded at mildly acidic pH values; whereas actively metabolizing biomass is resistant to NO2 (-) toxicity over a wide range of pH values.


Synergistic induction of cyclooxygenase-II by bacterial lipopolysaccharide in combination with particles of medical device materials in a murine macrophage cell line J774A.1.
Corrosion and wear of implanted medical devices may produce particulate debris, leading to acute and chronic inflammatory responses in the host. In the presence of biomaterial wear particles, host monocytes/macrophages are activated to synthesize or secrete mediators of inflammation. In order to understand the mechanisms underlying the host response to particulates and device-associated infections, we have focused on the effects of medical device particles on macrophage function, because these cells play a pivotal role in the body's response to foreign bodies and their interaction with other cellular components of the immune system. In order to evaluate the effects of particles of medical device materials on functional activities of macrophages, we developed a cyclooxygenase-II (COX-II) assay system using J774A.1 macrophages. Constitutive cyclooxygenase (COX-I) is present in cells under physiological conditions, whereas inducible COX-II is induced by some cytokines, mitogens, and endotoxin, presumably in pathological conditions such as inflammation. We have evaluated the inductive effects of implant materials, i.e., particles of polymethylmethacrylate (PMMA), hydroxyapatite (HA), titanium oxide, and silica, on the activity of COX-II using thin layer chromatography of prostaglandin D(2) (PGD(2)) formed from [1-(14)C]-labeled arachidonic acid (AA). Also, we have assessed the synergistic effects of these particles on lipopolysaccharide (LPS)-mediated macrophage activation. Addition of LPS to these particles increased PGD(2) production several-fold greater than the addition of any inducer alone. Our results indicated that device-associated infections could enhance inflammatory responses to the wear particles in subjects with medical implants or in whom particulate biomaterials are used for clinical purposes. The use of this model COX-II assay system may lead to the identification of inflammatory potentials for implant materials more specifically than present in vivo assays.


[Ultrasound fracture diagnosis--an experimental study].
Thanks to the increasing use of ultrasonography in the diagnostic evaluation of the musculoskeletal system, and the development of high-resolution ultrasonic transducers with ever better image quality, as well as the greater general trend towards non-invasive techniques, the use of ultrasonography in the diagnosis and follow-up of fractures would appear to make good sense. The aim of the present experimental study was, therefore, to identify the typical acoustic pattern of fractures and areas of bone impression and defects, while taking account of possible sources of error due to artefacts. Experiments were carried out on cadaver bones immersed in a water bath, using 7.5 and 10 MHz linear transducers. Depending on its size, the bony defect is represented by an interruption of the cortical echo, or a dorsal band of echoes limited to the fracture zone. Of interest is the fact that fractures and bony defects are not represented as such when the transducer is directed parallel to the line of the fracture or the impression area. Particular attention needs to be paid to the numerous artefacts occurring at the margins of the fracture. In summary, it may be noted that using resolution transducers under standardised experimental examination conditions, cortical interruptions of not less than 1 mm can be identified.


Pulmonary vasculitis in Hughes-Stovin syndrome (HSS): a reference atlas and computed tomography pulmonary angiography guide-a report by the HSS International Study Group.
Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by widespread venous/arterial thrombosis and pulmonary artery aneurysms (PAAs), which is associated with serious morbidity and mortality. All fatalities reported in HSS resulted from unpredictable fatal suffocating hemoptysis. Therefore, it is necessary to recognize pulmonary complications at an early stage of the disease. The aims of this study are to develop a reference atlas of images depicting the characteristic features of HSS by computed tomography pulmonary angiography (CTPA). To make a guide for physicians by developing a classification of PAAs according to the severity and risk of complications associated with each distinct lesion type. The Members of the HSS International Study Group (HSSISG) collected 42 cases, with high-quality CTPA images in one radiology station and made reconstructions from the source images. These detailed CTPA studies were reviewed for final image selection and approved by HSSISG board members. We classified these findings according to the clinical course of the patients. This atlas describes the CTPA images that best define the wide spectrum of pulmonary vasculitis observed in HSS. Pulmonary aneurysms were classified into six radiographic patterns: from true stable PAA with adherent in-situ thrombosis to unstable leaking PAA, BAA and/or PAP with loss of aneurysmal wall definition (most prone to rupture), also CTPA images demonstrating right ventricular strain and intracardiac thrombosis. The HSSISG reference atlas is a guide for physicians regarding the CTPA radiological findings, essential for early diagnosis and management of HSS-related pulmonary vasculitis. Key Points • The Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by extensive vascular thrombosis and pulmonary artery aneurysms (PAAs) that can lead to significant morbidity and mortality. • All fatalities reported in HSS were related to unpredictable massive hemoptysis; therefore, it is critical to recognize pulmonary complications at an early stage of the disease. • The HSS International Study Group reference atlas classifies pulmonary vasculitis in HSS at 6 different stages of the disease process and defines the different radiological patterns of pulmonary vasculitis notably pulmonary artery aneurysms, as detected by computed tomography pulmonary angiography (CTPA). • The main aim of the classification is to make a guide for physicians about this rare syndrome. Such a scheme has never been reached before since the first description of the syndrome by Hughes and Stovin since 1959. This classification will form the basis for future recommendations regarding diagnosis and treatment of this syndrome.


Mitochondrial translation and dynamics synergistically extend lifespan in C. elegans through HLH-30.
Mitochondrial form and function are closely interlinked in homeostasis and aging. Inhibiting mitochondrial translation is known to increase lifespan in C. elegans, and is accompanied by a fragmented mitochondrial network. However, whether this link between mitochondrial translation and morphology is causal in longevity remains uncharacterized. Here, we show in C. elegans that disrupting mitochondrial network homeostasis by blocking fission or fusion synergizes with reduced mitochondrial translation to prolong lifespan and stimulate stress response such as the mitochondrial unfolded protein response, UPRMT. Conversely, immobilizing the mitochondrial network through a simultaneous disruption of fission and fusion abrogates the lifespan increase induced by mitochondrial translation inhibition. Furthermore, we find that the synergistic effect of inhibiting both mitochondrial translation and dynamics on lifespan, despite stimulating UPRMT, does not require it. Instead, this lifespan-extending synergy is exclusively dependent on the lysosome biogenesis and autophagy transcription factor HLH-30/TFEB. Altogether, our study reveals the mechanistic crosstalk between mitochondrial translation, mitochondrial dynamics, and lysosomal signaling in regulating longevity.


Evaluation of the predictive reliability of a new watershed health assessment method using the SWAT model.
The purpose of watershed assessments is to give information about conditions of water quality, stream morphology, and biological integrity to identify the sources of stressors and their impacts. In recent decades, different watershed assessment methods have been developed to evaluate the cumulative impacts of human activities on watershed health and the condition of aquatic systems. In the current research, we propose a new approach for assessing watershed vulnerability to contamination based on spatial analysis by using geographic information systems (GIS) and the analytic hierarchy process (AHP) technique. This new procedure, designed to identify vulnerable zones, depends on six basic factors that represent watershed characteristics: land use/land cover, soil type, average annual precipitation, slope, depth to groundwater, and bedrock type. The general assumptions for assessing watershed vulnerability are based on the response of watersheds to different contamination impacts and how the six selected factors interact to affect watershed health. The new watershed vulnerability assessment technique was used to create maps showing the relative vulnerabilities of specific sub-watersheds in the Eagle Creek Watershed in central Indiana. The results showed a remarkable difference in watershed susceptibility between the sub-watersheds in their vulnerability to pollution. To test the reliability of the proposed vulnerability assessment technique, the SWAT (Soil and Water Assessment Tool) model was applied to predict the water quality in each sub-watershed. Using the SWAT model, some parameters (e.g., total suspended solids [TSS] and nitrate) were tested based on the availability of the data needed for comparison. Both the SWAT and the newly proposed method produced good results in predicting water quality loads, which validated the proposed method. Hence, the results of the evaluation of the predictive reliability of the watershed vulnerability assessment method revealed that the proposed approach is suitable as a decision-making tool to predict watershed health.


Prognostic value of proliferating cell nuclear antigen (PCNA) in infiltrating ductal carcinoma breast.
To assess the independent and interdependent prognostic value of proliferating cell nuclear antigen (PCNA) in carcinoma of breast in our female population and its association with pathologic variables and disease outcome. A descriptive study. Section of Histopathology, Department of Pathology and Microbiology, The Aga Khan University, Karachi from January 1992 to December 1997. All cases diagnosed with invasive ductal carcinomas (IDC) of breast with lymph nodes sampling were included. The expression of PCNA was analyzed on tumor specimens of IDC breast. These patients also had axillary lymph node sampling. The expression of PCNA protein was analyzed immunohistochemically by PAP technique. Patients were followed for a median duration of 48 months. The percentage of PCNA positive tumor cells was estimated semi-quantitatively. Positivity was seen in every case, mean PCNA positivity was 27% (range 10-80) with a median of 28%. The <25% positivity was seen in 149 (47%) cases, and >25% positivity seen in 166 (53%) cases. According to the pathological grading lowest mean PCNA was seen in grade-I i.e., 26% tumor cells showed nuclear reactivity to PCNA followed by grade-II 30% and grade-III 33%. PCNA categorical expression was significantly correlated with histological differentiation, (p<0.05) and tumor size (p<0.01). Distant metastases were seen in>25% positive cases (p<0.05). PCNA expression when correlated with overall survival, showed significant correlation between categorical PCNA (p<0.05). At a median follow-up of 48 months, 66% of <25 PCNA positive patients died with an overall survival of 3.16 years and disease-free survival of 2.5 years, among >25% PCNA positive patients 77% died with an overall survival of 2.7 years and a disease-free survival of 2.2 years. In this study PCNA proved to be an independent prognostic indicator in predicting disease-free and overall survival in breast carcinoma patients.


Development of the Taiwanese version of the Health Enhancement Lifestyle Profile (HELP-T).
To develop and validate a Taiwanese version of the Health Enhancement Lifestyle Profile (HELP-T) for community-dwelling older Taiwanese adults (≥ 55 years). The original Health Enhancement Lifestyle Profile (HELP) is a 56-item self-report questionnaire measuring various aspects of health-related lifestyles in older adults. The standard cultural-adaptation procedure was used for questionnaire translation and modification. A field test was conducted for culturally specific item selection, rating-scale analysis, and psychometric validation of the HELP-T in a sample of 274 community-dwelling older adults via classical test theory. The 59-item HELP-T is culturally adapted from the original 56-item HELP. The original 6-point rating scale was modified to a 3-point scale for easy use by Taiwanese older adults. The HELP-T had good internal consistency (Cronbach's alpha = 0.82). The test-retest reliability for the total score was high (0.92), and moderate to high (range: 0.57-0.92) for subscales. The construct validity was supported by the significant correlations between each subscale and the total score (Spearman's rho = 0.41-0.67, p < 0.0001) and by the ability of the scores to significantly discriminate between participants with different levels of self-rated health (p = 0.0001). The HELP-T is a suitable clinical tool for assessing and monitoring lifestyle risk factors, establishing client-centered lifestyle intervention goals, and determining the outcomes of lifestyle interventions.


Mutations Located outside the Integrase Gene Can Confer Resistance to HIV-1 Integrase Strand Transfer Inhibitors.
Resistance to the integrase strand transfer inhibitors raltegravir and elvitegravir is often due to well-identified mutations in the integrase gene. However, the situation is less clear for patients who fail dolutegravir treatment. Furthermore, most in vitro experiments to select resistance to dolutegravir have resulted in few mutations of the integrase gene. We performed an in vitro dolutegravir resistance selection experiment by using a breakthrough method. First, MT4 cells were infected with human immunodeficiency virus type 1 (HIV-1) Lai. After integration into the host cell genome, cells were washed to remove unbound virus and 500 nM dolutegravir was added to the cell medium. This high concentration of the drug was maintained throughout selection. At day 80, we detected a virus highly resistant to dolutegravir, raltegravir, and elvitegravir that remained susceptible to zidovudine. Sequencing of the virus showed no mutations in the integrase gene but highlighted the emergence of five mutations, all located in the nef region, of which four were clustered in the 3' polypurine tract (PPT). Mutations selected in vitro by dolutegravir, located outside the integrase gene, can confer a high level of resistance to all integrase inhibitors. Thus, HIV-1 can use an alternative mechanism to develop resistance to integrase inhibitors by selecting mutations in the 3' PPT region. Further studies are required to determine to what extent these mutations may explain virological failure during integrase inhibitor therapy.IMPORTANCE Integrase strand transfer inhibitors (INSTIs) are increasingly used both as first-line drugs and in rescue therapy because of their low toxicity and high efficacy in both treatment-naive and treatment-experienced patients. Until now, resistance mutations selected by INSTI exposure have either been described in patients or selected in vitro and involve the integrase gene. Most mutations selected by raltegravir, elvitegravir, or dolutegravir exposure are located inside the catalytic site of the integrase gene, but mutations outside the catalytic site of the integrase gene have also been selected with dolutegravir. Following in vitro selection with dolutegravir, we report, for the first time, a virus with selected mutations outside the HIV-1 integrase gene that confer resistance to all integrase inhibitors currently used to treat patients, such as raltegravir, elvitegravir, and dolutegravir. Our observation may explain why some viruses responsible for virological failure in patients treated with dolutegravir did not show mutations in the integrase gene.


Activation of TGF-β signaling induces cell death via the unfolded protein response in Fuchs endothelial corneal dystrophy.
Fuchs endothelial corneal dystrophy (FECD) is a slowly progressive bilateral disease of corneal endothelium in which accumulation of extracellular matrix (ECM) and loss of corneal endothelial cells (CECs) are phenotypic features. The corneal endothelium maintains corneal transparency by regulating water hydration; consequently, corneal endothelial dysfunction causes serious vision loss. The only therapy for corneal haziness due to corneal endothelial diseases, including FECD, is corneal transplantation using donor corneas, and no pharmaceutical treatment is available. We provide evidence that the expression levels of transforming growth factor-β (TGF-β) isoforms and TGF-β receptors are high in the corneal endothelium of patients with FECD. A cell model based on patients with FECD shows that TGF-β signaling induced a chronic overload of ECM proteins to the endoplasmic reticulum (ER), thereby enhancing the formation of unfolded protein and triggering the intrinsic apoptotic pathway through the unfolded protein response (UPR). We propose that inhibition of TGF-β signaling may represent a novel therapeutic target that suppresses cell loss as well as the accumulation of ECM in FECD.


Mouse cognition-related behavior in the open-field: emergence of places of attraction.
Spatial memory is often studied in the Morris Water Maze, where the animal's spatial orientation has been shown to be mainly shaped by distal visual cues. Cognition-related behavior has also been described along "well-trodden paths"--spatial habits established by animals in the wild and in captivity reflecting a form of spatial memory. In the present study we combine the study of Open Field behavior with the study of behavior on well-trodden paths, revealing a form of locational memory that appears to correlate with spatial memory. The tracked path of the mouse is used to examine the dynamics of visiting behavior to locations. A visit is defined as either progressing through a location or stopping there, where progressing and stopping are computationally defined. We then estimate the probability of stopping at a location as a function of the number of previous visits to that location, i.e., we measure the effect of visiting history to a location on stopping in it. This can be regarded as an estimate of the familiarity of the mouse with locations. The recently wild-derived inbred strain CZECHII shows the highest effect of visiting history on stopping, C57 inbred mice show a lower effect, and DBA mice show no effect. We employ a rarely used, bottom-to-top computational approach, starting from simple kinematics of movement and gradually building our way up until we end with (emergent) locational memory. The effect of visiting history to a location on stopping in it can be regarded as an estimate of the familiarity of the mouse with locations, implying memory of these locations. We show that the magnitude of this estimate is strain-specific, implying a genetic influence. The dynamics of this process reveal that locations along the mouse's trodden path gradually become places of attraction, where the mouse stops habitually.


Dermal Delivery of Selected Polyphenols from Silybum marianum. Theoretical and Experimental Study.
Silymarin is a well-known standardized extract from the seeds of milk thistle (Silybum marianum L., Asteraceae) with a pleiotropic effect on human health, including skin anticancer potential. Detailed characterization of flavonolignans properties affecting interactions with human skin was of interest. The partition coefficients log Pow of main constitutive flavonolignans, taxifolin and their respective dehydro derivatives were determined by a High Performance Liquid Chromatography (HPLC) method and by mathematical (in silico) approaches in n-octanol/water and model lipid membranes. These parameters were compared with human skin intake ex vivo. The experimental log Pow values for individual diastereomers were estimated for the first time. The replacement of n-octanol with model lipid membranes in the theoretical lipophilicity estimation improved the prediction strength. During transdermal transport, all the studied compounds permeated the human skin ex vivo; none of them reached the acceptor liquid. Both experimental/theoretical tools allowed the studied polyphenols to be divided into two groups: low (taxifolin, silychristin, silydianin) vs. high (silybin, dehydrosilybin, isosilybin) lipophilicity and skin intake. In silico predictions can be usefully applied for estimating general lipophilicity trends, such as skin penetration or accumulation predictions. However, the theoretical models cannot yet provide the dermal delivery differences of compounds with very similar physico-chemical properties; e.g., between diastereomers.


The use of breath tests in the study of malabsorption.
Breath analysis has evolved into a technique that can support nicely the evaluation of patients with diarrhoea and/or weight loss and in whom nutrient malabsorption is a possibility. The lactose and sucrose breath hydrogen tests offer direct (and probably the most sensitive) documentation of the malabsorption of carbohydrate and are currently widely used for clinical analysis. The 14C-xylose breath test is the most sensitive and specific breath test for detecting bacterial overgrowth; it may be used in combination with the labelled bile acid breath test to make the latter a sensitive and specific test for ileal malabsorption of bile salts. The labelled fat breath test has promise in aiding the detection and/or cause of fat malabsorption, but requires modification for optimum sensitivity and utility in quantifying the level of fat absorption.


Topical Capsaicin for Treating Cannabinoid Hyperemesis Syndrome.
Cannabinoid hyperemesis syndrome (CHS), associated with chronic cannabis use, presents with cyclic abdominal pain, nausea, and vomiting. With increasing use of marijuana, the incidence of CHS is expected to increase. Most patients with CHS make frequent visits to the emergency room and are usually refractory to conventional treatment. We, therefore, present a case of CHS successfully treated with topical capsaicin application. Case Presentation. A 41-year-old female with a recent excess use of cannabis presented to the emergency department for evaluation of recurrent excruciating epigastric pain accompanied by severe nausea and vomiting. She had similar, milder symptoms a year ago and underwent endoscopic evaluation which was negative except for mild reflux esophagitis for which she was started on a proton pump inhibitor. On this presentation, basic laboratory workup, EKG, and CT scan of abdomen and pelvis were unremarkable. A detailed abdominal exam was only positive for mild epigastric tenderness. She was instructed to continue pantoprazole and pain medication and outpatient repeat esophagogastroduodenoscopy. The patient returned the next day with extreme retching, nausea, and vomiting and was admitted for further evaluation. Intravenous fluids, antiemetics, and morphine were started for pain control with no symptomatic improvement. A diagnosis of cannabis hyperemesis syndrome was made based on history of chronic marijuana use and otherwise negative workup. A trial of topical capsaicin, over the epigastric region, was tried that provided dramatic relief within 24 hours. Repeat endoscopic evaluation had no evidence of ulcers, celiac disease, or esophagitis. She was discharged on topical capsaicin and counselled on marijuana abstinence, with no return of symptoms. Based on the dramatic resolution of symptoms with topical capsaicin, our case supports this promising intervention and provides an alternate approach to antiemetics and narcotics routinely used in patients with cannabis hyperemesis syndrome.


Clinical onset of celiac disease after an episode of Campylobacter jejuni enteritis.
The present report describes a young woman with no previous gastrointestinal complaints who was initially diagnosed with postinfective irritable bowel syndrome (IBS) after a confirmed case of Campylobacter jejuni enteritis. However, because of persistent diarrhea, new-onset bloating and the development of iron and vitamin deficiencies, serological markers for celiac disease (CD) were evaluated. A positive tissue transglutaminase immunoglobulin A antibody test and repeat endoscopy with duodenal biopsy showing a Marsh IIIa lesion confirmed the diagnosis of CD. Infectious gastroenteritis is a well-established risk factor for the development of IBS, and there is recent evidence that it could play a role in the initiation and exacerbation of inflammatory bowel disease. The present case suggests that the clinical expression of CD can be unmasked by an acute gastrointestinal infection and supports the hypothesis that environmental factors other than gliadin may play a role in the clinical onset of CD in a genetically susceptible host. The increasing availability of serological testing and upper endoscopy has led to increasingly frequent diagnoses of CD and recognition that it may mimic IBS. The present case findings suggest that CD should be considered in the differential diagnosis of persistent IBS-like symptoms after an episode of infectious gastroenteritis.


Sodium polystyrene sulfonate used to reduce the potassium content of a high-protein enteral formula: a quantitative analysis.
Sodium polystyrene sulfonate (Kayexalate) commonly is used in treating hyperkalemia. As a cation exchange resin, it also can be used to reduce the potassium content of enteral nutrition formulas. This study evaluates the use of Kayexalate to reduce potassium in one high-protein enteral formula and describes the quantitative analysis of the product. Sodium polystyrene sulfonate and enteral formula were mixed into a slurry and allowed to settle, and then the supernatant was decanted off and tested as samples. Three sample concentrations were analyzed: a control not subjected to potassium reduction, 0.5 g of Kayexalate per mEq K+ sample, and a 1 g/mEq K+ sample. Of these samples, moisture, lipid, protein, carbohydrate, ash, and mineral content were obtained. Compared with the control, the percentage decrease of potassium ranged from 25% to 36%, depending on the concentration of Kayexalate. A significant increase of 324% in sodium concentration was found in the 1.0 g/mEq K+ sample. Although there was no change in magnesium content, a slight increase in phosphorus, iron, and zinc was evident. The treatment of an enteral formula with sodium polystyrene sulfonate significantly increases its sodium content, with a modest decrease in potassium content. Clinicians using this method in clinical practice should be aware of the increase in sodium content.


[Factors associated with fetal brain-sparing effect in patients with hypertension in pregnancy].
To determine perinatal outcomes and factors associated with fetal brain sparing effect diagnosed by Doppler flow velocimetry in patients with arterial hypertension. We performed a cross-sectional retrospective study including 129 pregnant women with arterial hypertension and submitted to Doppler flow velocimetry, within fifteen days before delivery. Women with multiple pregnancies, fetal malformations, genital bleeding, placenta praevia, premature rupture of membranes, smoking, illicit drug use and chronic diseases were excluded. We analyzed the biological, socio-demographic and obstetric characteristics, as well the perinatal outcomes. To determine the association between variables, we used the χ² test, Fisher's exact test and Student's t-test. Multiple logistic regression analysis was performed to determine the factors associated with fetal centralization. Pre-eclampsia was the most frequent hypertensive disorder (53.5%) and fetal brain sparing effect was observed in 24.0% of fetuses. The prenatal factors associated with fetal brain sparing were the persistence of bilateral protodiastolic notches in uterine arteries (OR 3.6; 95%CI 1.4 - 9.4; p=0.009) and intrauterine growth restriction (IUGR) (OR 3.3; 95%CI 1.2 - 9.3; p=0.02). The perinatal outcomes associated with fetal brain sparing were gestational age <32 weeks, small for gestational age (SGA) infants, birth weight <2,500 g and perinatal death. There was no association with other maternal or neonatal variables. The main factors associated with fetal brain sparing were persistence of uterine arteries notches, IUGR, and increased frequency of adverse perinatal outcomes.


Cognitive outcomes and age of detection of severe mucopolysaccharidosis type 1.
The US Secretary of Health and Human Services recommended in February 2016 that mucopolysaccharidosis type 1 (MPS I) be added to the recommended uniform screening panel for state newborn screening programs. One of the key factors in this decision was the evidence suggesting that earlier treatment with hematopoietic cell transplantation (HCT) for the most severe form, Hurler syndrome (MPS IH), would lead to improved cognitive outcomes. Consistent evidence from peer-reviewed studies suggests that transplantation in the first year of life is associated with improved developmental quotient or intelligence quotient and continued cognitive growth, with earlier age of treatment associated with improved outcomes. However, available evidence suggests that cognitive functioning and attention can still lag behind unaffected age-matched children, leading to the need for special education services. Verbal and nonverbal cognitive abilities outcomes may be affected differently by HCT. With the recent addition of MPS I to the recommended uniform screening panel, future work is needed to evaluate the impact of earlier, presymptomatic detection and treatment initiation and other supportive therapies on cognitive outcomes.Genet Med advance online publication 26 January 2017.


Simulation of dynamic orofacial movements using a constitutive law varying with muscle activation.
This paper presents a biomechanical model of the face to simulate orofacial movements in speech and non-verbal communication. A 3D finite element model, based on medical images of a subject, is presented. A hyperelastic Mooney-Rivlin constitutive law accounts for the non-linear behaviour of facial tissue. Muscle fibres are represented by piece-wise uniaxial tensile element that generate force. The stress stiffening effect, an increase in the stiffness of the muscles when activated, is modelled by varying the constitutive law of the tissue with the level of activation of the muscle. A large number of facial movements occurring during speech and facial mimics are simulated. Results show that our modelling approach provides a realistic account of facial mimics. The differences between dynamic vs. quasi-static simulations are also discussed, proving that dynamic trajectories better fit experimental data.


Immunomultiple PCR-based electrochemical and lateral flow strategy for the simultaneous detection of liver cancer tumor markers.
The current use of the single serum biomarker α-fetoprotein (AFP) in clinical practice has limitations in terms of specificity and sensitivity. We propose a strategy that combines antigen capture polymerase chain reaction (AC-PCR), lateral flow assay (LFA), and electrochemical biosensors to detect both AFP and circulating tumor cells (CTCs) in liver cancer serum. First, we used the AC-PCR technique to achieve target separation, purification, signal conversion, and amplification, eliminating target heterogeneity. Then, we achieved rapid results through the LFA and electrochemical biosensor platforms. As a result, the proposed assay has limits of 5 cells/mL for CTCs and 5 µg/L for AFP. The proposed method was applied effectively to simulated blood samples. This method has the potential to play a role in early liver cancer and provide a potential application for the diagnosis and precision treatment of liver cancer.


MTDN: Learning Multiple Temporal Dynamics Representation for Emotional Valence Classification with EEG.
Emotion recognition from electroencephalogram (EEG) requires computational models to capture the crucial features of the emotional response to external stimulation. Spatial, spectral, and temporal information are relevant features for emotion recognition. However, learning temporal dynamics is a challenging task, and there is a lack of efficient approaches to capture such information. In this work, we present a deep learning framework called MTDN that is designed to capture spectral features with a filterbank module and to learn spatial features with a spatial convolution block. Multiple temporal dynamics are jointly learned with parallel long short-term memory (LSTM) embedding and self-attention modules. The LSTM module is used to embed the time segments, and then the self-attention is utilized to learn the temporal dynamics by intercorrelating every embedded time segment. Multiple temporal dynamics representations are then aggregated to form the final extracted features for classification. We experiment on a publicly available dataset, DEAP, to evaluate the performance of our proposed framework and compare MTDN with existing published results. The results demonstrate improvement over the current state-of-the-art methods on the valence dimension of the DEAP dataset.


Genetic Studies of Actinic Keratosis Development: Where Are We Now?
Actinic keratosis (AK) is a common precancerous skin lesion that can develop into cutaneous squamous cell carcinoma (CSCC). AK is characterized by atypical keratinocytes in the skin's outer layer and is commonly found in sun-exposed areas. Like many precancerous lesions, the development of AK is closely associated with genetic mutations. The molecular biology and transcriptional mechanisms underlying AK development are not well understood. Ultraviolet (UV) light exposure, especially UVA and UVB radiation, is a significant risk factor for AK, causing DNA damage and mutagenic effects. Besides UV exposure, comorbidities like diabetes, rheumatoid arthritis, and psoriasis may also influence AK development. AK patients have shown associations with various internal malignancies, indicating potential vulnerability in cancer-associated genes. Treatment for AK includes cryosurgery, electrodesiccation and curettage, chemotherapeutic creams, photodynamic therapy, or topical immune-modulators. Genomic studies have identified genetic aberrations in AK, with common mutations found in genes like TP53, NOTCH1, and NOTCH2. The progression from AK to CSCC involves chromosomal aberrations and alterations in oncogenes and tumor-suppressor genes. The functional relationships among these genes are not fully understood, but network analysis provides insights into their potential mechanisms. Further research is needed to enhance our understanding of AK's pathogenesis and develop novel therapeutic approaches.


A Self-Regulating DNA Rotaxane Linear Actuator Driven by Chemical Energy.
Nature-inspired molecular machines can exert mechanical forces by controlling and varying the distance between two molecular subunits in response to different inputs. Here, we present an automated molecular linear actuator composed of T7 RNA polymerase (T7RNAP) and a DNA [2]rotaxane. A T7 promoter region and terminator sequences are introduced into the rotaxane axle to achieve automated and iterative binding and detachment of T7RNAP in a self-controlled fashion. Transcription by T7RNAP is exploited to control the release of the macrocycle from a single-stranded (ss) region in the T7 promoter to switch back and forth from a static state (hybridized macrocycle) to a dynamic state (movable macrocycle). During transcription, the T7RNAP keeps restricting the movement range on the axle available for the interlocked macrocycle and prevents its return to the promotor region. Since this range is continuously depleted as T7RNAP moves along, a directional and active movement of the macrocycle occurs. When it reaches the transcription terminator, the polymerase detaches, and the system can reset as the macrocycle moves back to hybridize again to the ss-promoter docking site. The hybridization is required for the initiation of a new transcription cycle. The rotaxane actuator runs autonomously and repeats these self-controlled cycles of transcription and movement as long as NTP-fuel is available.