Identification of hub genes associated with the pathogenesis of diffuse large B-cell lymphoma subtype one characterized by host response via integrated bioinformatic analyses.
Host response diffuse large B-cell lymphoma (HR DLBCL) shares features of histologically defined T-cell/histiocyte-rich B-cell lymphoma, including fewer genetic abnormalities, frequent splenic and bone marrow involvement, and younger age at presentation. HR DLBCL is inherently less responsive to the standard treatment for DLBCL. Moreover, the mechanism of infiltration of HR DLBCL with preexisting abundant T-cells and dendritic cells is unknown, and their associated underlying immune responses incompletely defined. Here, hub genes and pathogenesis associated with HR DLBCL were explored to reveal molecular mechanisms and treatment targets. Differentially expressed genes were identified in three datasets (GSE25638, GSE44337, GSE56315). The expression profile of the genes in the GSE53786 dataset was used to constructed a co-expression network. Protein-protein interactions analysis in the modules of interest identified candidate hub genes. Then screening of real hub genes was carried out by survival analysis within the GSE53786 and GSE10846 datasets. Expression of hub genes was validated in the Gene expression profiling interactive analysis, Oncomine databases and human tissue specimens. Functional enrichment analysis and Gene set enrichment analysis were utilized to investigate the potential mechanisms. Tumor Immune Estimation Resource and The Cancer Genome Atlas were used to mine the association of the hub gene with tumor immunity, potential upstream regulators were predicted using bioinformatics tools. A total of 274 common differentially expressed genes were identified. Within the key module, we identified CXCL10 as a real hub gene. The validation of upregulated expression level of CXCL10 was consistent with our study. CXCL10 might have a regulatory effect on tumor immunity. The predicted miRNA (hsa-mir-6849-3p) and transcription factor (IRF9) might regulate gene expression in the hub module.


Preclinical rationale for PI3K/Akt/mTOR pathway inhibitors as therapy for epidermal growth factor receptor inhibitor-resistant non-small-cell lung cancer.
Mutations in the epidermal growth factor receptor gene (EGFR) are frequently observed in non-small-cell lung cancer (NSCLC), occurring in about 40% to 60% of never-smokers and in about 17% of patients with adenocarcinomas. EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, have transformed therapy for patients with EGFR-mutant NSCLC and have proved superior to chemotherapy as first-line treatment for this patient group. Despite these benefits, there are currently 2 key challenges associated with EGFR inhibitor therapy for patients with NSCLC. First, only 85% to 90% of patients with the EGFR mutation derive clinical benefit from EGFR TKIs, with the remainder demonstrating innate resistance to therapy. Second, acquired resistance to EGFR TKIs inevitably occurs in patients who initially respond to therapy, with a median duration of response of about 10 months. Mutant EGFR activates various subcellular signaling cascades, including the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, which demonstrates maintained activity in a variety of TKI-resistant cancers. Given the fundamental role of the PI3K/Akt/mTOR pathway in tumor oncogenesis, proliferation, and survival, PI3K pathway inhibitors have emerged as a possible solution to the problem of EGFR TKI resistance. However resistance to EGFR TKIs is associated with considerable heterogeneity and complexity. Preclinical experiments investigating these phenomena suggest that in some patients, PI3K inhibitors will have to be paired with other targeted agents if they are to be effective. This review discusses the preclinical data supporting PI3K/Akt/mTOR pathway inhibitor combinations in EGFR TKI-resistant NSCLC from the perspective of the various agents currently being investigated in clinical trials.


Development of novel enzyme potentiometric biosensor based on pH-sensitive field-effect transistors for aflatoxin B1 analysis in real samples.
This study aimed at the development and optimization of a potentiometric biosensor based on pH-sensitive field-effect transistors and acetylcholinesterase for aflatoxin B1 determination in real samples. Optimal conditions for bioselective elements operation were defined and analytical characteristics of the proposed biosensor were studied. The proposed biosensor characterized high operational stability and reproducibility of signal. Selectivity of acetylcholinesterase-biosensor to aflatoxins in relation to other groups of toxic substances was analyzed. The developed biosensor was applied to the determination of aflatoxin B1 in real samples (sesame, walnut and pea).


Low-dose arsenite causes overexpression of EGF, TGFα, and HSP90 through Trx1-TXNIP-NLRP3 axis mediated signaling pathways in the human bladder epithelial cells.
Epidemiological studies have demonstrated an increased incidence of bladder cancer in arseniasis- endemic areas; however, the precise molecular mechanisms remain unknown. Our previous results have shown that the protein levels of EGF, TGFα, and HSP90 in arsenite-treated bladder uroepithelial cells increased markedly and contributed to hyperactivation of EGF receptors. The aim of this study was to further explore the regulatory ways underlying overexpression of EGF, TGFα, and HSP90 in these cells. The present results showed that both Trx and GSH systems were stimulated in arsenite-treated cells, and ROS levels in 2 μM arsenite-treated cells did not changed obviously; however, ROS levels in 4 μM arsenite-treated cells increased significantly. By using the antioxidant and specific inhibitors, we found that in 2 μM arsenite-treated cells, JNK/NF-κB signaling pathway was involved in overexpression of EGF and TGFα, and ERK/NF-κB signaling pathway contributed to HSP90 overexpression, however in 4 μM arsenite-treated cells, both ERK/ and JNK/NF-κB signaling pathways were involved in overexpression of EGF, TGFα, and HSP90, and PI3K/AKT/NF-κB signaling pathway contributed to overexpression of EGF and TGFα. Furthermore, our results also showed that the Trx1-TXNIP-NLRP3 axis was activated in arsenite-treated cells, and played a pivotal role in activation of the signaling pathways involved in overexpression of EGF, TGFα, and HSP90. In conclusion, the Trx1-TXNIP-NLRP3 axis might be activated by arsenite-induced redox imbalance in bladder uroepithelial cells, and mediate the activation of signaling pathways involved in overexpression of EGF, TGFα, and HSP90.


Guidelines versus trial-evidence for statin use in primary prevention: The Copenhagen General Population Study.
Guideline-recommended use of risk calculators to select for statin therapy in primary prevention has never been tested in a randomized controlled trial (RCT). We determined the extent to which guideline-based statin recommendations from the American College of Cardiology/American Heart Association (ACC/AHA), Canadian Cardiovascular Society(CCS), UK National Institute for Health and Care Excellence (NICE), and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) is supported by available evidence from RCTs. 79,171 individuals from the Copenhagen General Population Study who were free of ASCVD and statin use at baseline were included. RCT evidence supporting guideline-recommended statin allocation and the estimated number needed to treat (NNT) to prevent one ASCVD event were assessed. During 8.2 years of follow-up, 4031 ASCVD events occurred. Of individuals eligible for statin therapy with the ACC/AHA, CCS, NICE and ESC/EAS guidelines, 86%, 88%, 88% and 84% had direct RCT evidence of statin efficacy, respectively (guideline-positive&RCT-positive). This group represented 26-37% of all 79,171 individuals, while guideline-positive&RCT-negative individuals represented 5-7%, guideline-negative&RCT-positive individuals 28-39%, and guideline-negative&RCT-negative individuals represented 30-31%. The ASCVD events per 1000 person-years were 11.4-12.7 (guideline-positive&RCT-positive), 6.3-8.0 (guideline-positive&RCT-negative), 4.2-5.2 (guideline-negative&RCT-positive), and 2.3-2.5 (guideline-negative&RCT-negative), respectively, while the corresponding NNT to prevent one event in 10 years using high-intensity statin were 19-21, 30-32, 48-60, and 105-125, respectively. The far majority of individuals eligible for guideline-recommended primary prevention with statins have direct RCT evidence supporting statin use. Allocating statins based on guideline-criteria is more efficient with lower NNT for preventing ASCVD events than allocating statin therapy based solely on RCT evidence.


HeLa cell RNA and protein syntheses. Effects of long-term treatment with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB).
The population growth rate of HeLa cells treated with 60 microM 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) in reinforced Eagle's minimum essential medium was directly related to the concentration of fetal bovine serum in the range from 5 to 30%. Control cells proliferated at a maximal rate (doubling time: 18-19 hr) at serum concentrations in this range. In 60 microM DRB-containing medium supplemented with 5% serum, the inhibition of hnRNA synthesis after 1,5, and 48 hr of treatment was equivalent to 78, 84, and 51%, respectively, whereas that of protein synthesis was equivalent to 5, 41, and 49%. In 15% serum, the inhibition of hnRNA synthesis after 1, 5, and 48 hr of treatment was equivalent to 75, 79, and 40%, whereas that of protein synthesis was equivalent to 13, 30, and 21%. Thus, after 48 hr of treatment of cells with DRB in either 5 or 15% serum, hnRNA synthesis was less inhibited than it was after 1 or 5 hr of treatment, and the level of protein synthesis in DRB-treated cells did not decrease between the 5th and 48th hr. After 48 hr of treatment of cells with DRB in 15% serum, hnRNA and protein syntheses were both somewhat less inhibited than after treatment in 5% serum. These results suggest that, on prolonged treatment, HeLa cells undergo a partial, serum-dependent adaptation to the inhibitor.


Impact of malaria on glutathione peroxidase levels: a systematic review and meta-analysis.
The primary antioxidant, glutathione peroxidase (GPx), is hypothesized to contribute to the pathophysiology of malaria. This current study conducted a meta-analysis to examine variations in GPx blood levels in malaria patients. Seven electronic databases-ProQuest, Scopus, Embase, MEDLINE, PubMed, Ovid, and Google Scholar-were searched for relevant studies with no limitations to publication language or publication date. The Joanna Briggs Institute critical appraisal tools were used to appraise the risk of bias among the included studies critically. The meta-analysis was conducted by pooling the effect estimates and Hedges's g using a random-effects model. Search results returned 1253 articles, of which 16 studies were used for syntheses. Results of the meta-analysis indicated that malaria patients had decreased blood levels of GPx compared to uninfected individuals (P < 0.01, Hedges' g: - 4.06, 95% CI - 5.49-(- 2.63), I2: 99.07%, 1278 malaria patients/627 uninfected individuals, 15 studies). Subgroup analyses indicated that peripheral levels of GPx were significantly diminished in patients with P. falciparum malaria compared to uninfected controls (P < 0.01, Hedges' g: - 3.06, 95% CI - 4.46-(- 1.65), I2: 98.39%, 9 studies) but not in patients with P. vivax malaria (P = 0.15, Hedges' g: - 2.05, 95% CI - 4.83-0.74), I2: 98.64%, 2 studies) Overall, malaria is associated with declined levels of GPx, particularly in patients with P. falciparum malaria. The finding provides valuable insights that prompt the need to investigate the role of GPx depletion in malaria pathogenesis.


Emergence of antibiotic resistance in immunocompromised host populations: A case study of emerging antibiotic resistant tuberculosis in AIDS patients.
The evolution of antibiotic resistance is far outpacing the development of new antibiotics, causing global public health concern about infections that will increasingly be unresponsive to antimicrobials. This risk of emerging antibiotic resistance may be meaningfully altered in highly AIDS-immunocompromised populations. Such populations fundamentally alter the bacterial evolutionary landscape in two ways, which we seek to model and analyze. First, widespread, population-level immunoincompetence creates a novel host environment with disrupted selective pressures. Second, within AIDS-prevalent populations, the recommendation that antibiotics be taken to treat and prevent opportunistic infection raises the risk of selection for drug-resistant pathogens. To determine the impact of HIV/AIDS on the emergence of antibiotic resistance-specifically in the developing world where high prevalence and economic challenges complicate disease management. We present an SEIR epidemiological model of bacterial infection, and parametrize it to capture HIV/AIDS-attributable emergence of resistance under conditions of both high and low HIV/AIDS prevalence. We demonstrate that HIV/AIDS-immunocompromised hosts can be responsible for a disproportionately greater contribution to emergence of resistance than would be expected based on population-wide HIV/AIDS prevalence alone. As such, the AIDS-immunocompromised have the potential become wellsprings of novel, resistant, opportunistic pathogen strains that can propagate into the broader global community. We discuss how public health policies for HIV/AIDS management can shape the evolutionary environment for opportunistic bacterial infections.


From old alkylating agents to new minor groove binders.
Alkylating agents represent the oldest class of anticancer agents with the approval of mechloretamine by the FDA in 1949. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in the treatment of specific malignancies, sometimes representing the unique option for the treatment of refractory tumors. Here, we are reviewing the major classes of alkylating agents, with a particular focus on the latest generations of compounds that specifically target the minor groove of the DNA. These naturally occurring derivatives have a unique mechanism of action that explains the recent regain of interest in developing new classes of alkylating agents that could be used in combination with other anticancer drugs to enhance tumor response in the clinic.


Effect of hyperfunctional occlusal loads on periodontium: A three-dimensional finite element analysis.
The periodontal tissue reaction to variations in occlusal forces has been described in the literature wherein clinical and histologic changes are discussed that produced due to stresses in the periodontal structures. Unfortunately, these stresses are not quantified. The aim of this study is to determine the stress produced on various periodontal tissues at different occlusal loads using finite element model (FEM) study. Four FEMs of maxillary incisor were designed consisting of the tooth, pulp, periodontal ligament (PDL), and alveolar bone at the various level of bone height (25%, 50%, and 75%). Different occlusal load (15 and 29 kg) at an angle of 50° to the long axis of the tooth was applied on the palatal surface at the level of middle third of the crown. All the models were assumed to be isotropic, linear, and elastic, and the analysis was performed on a Pentium IV processor computer using the ANSYS software. At normofunction load, the stresses were maximum on the mesial side near the cervical region at point D for tooth (-10.93 Mpa) for PDL (-4.06 Mpa) for bone (-4.3 Mpa) with normal bone levels as the bone levels decreased the stresses increased and the stresses tend to concentrate at the apical region. At any given point, the stresses were increased by 90% at hyperfunctional load. Based on the findings of the present study, there is reasonably good attempt to express numerical data of stress to be given normal occlusal and hyperfunctional loads to simulate clinical occlusal situations which are known to be responsible for healthy and diseased periodontium.


N-nitrosamines and nitrosatable amines, potential precursors of N-nitramines, in children's pacifiers and baby-bottle nipples.
Sixteen types of children's pacifiers and baby-bottle nipples, bought in shops in Israel but produced both there and elsewhere in the world, were analyzed for their contents of N-nitrosamines, which have been shown to be potent carcinogens in animals, and of nitrosatable amines. Two methods were used: one, originating in the United States, involved dichloromethane extraction of total volatile N-nitrosamines from the nipples and pacifiers, and the other, from the Federal Republic of Germany, consisted of analysis of N-nitrosamines and their amine precursors that migrated into artificial saliva. N-Nitrosodibutylamine (NDBA). N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA). N-nitrosopiperidine (NPIP), and N-nitrosopyrrolidine (NPYR) were detected by the first method, at individual levels as high as 369 ppb. Using the second method, NDBA, NDEA, NDMA, and N-nitrosomorpholine (NMOR) were detected at concentrations up to 41 ppb, in addition to the three nitrosatable amines dibutylamine, diethylamine, and dimethylamine. Upon nitrosation in the artificial saliva, these amines produced not only the related N-nitrosamines but also relatively high levels of the corresponding N-nitramines (N-nitrodibutylamine, N-nitrodiethylamine, and N-nitrodimethylamine), probably formed by oxidation of the N-nitrosamines by peroxides used for vulcanization of elastomers. Thus, if N-nitramines are not measured in addition to N-nitrosamines after nitrosation, the second method may underestimate the quantities of nitrosatable amines present in artificial saliva extracts. Whether N-nitramines, some of which have been shown to be both mutagenic and carcinogenic, also occur in the saliva of babies exposed to these products remains to be confirmed. Of the samples tested, 50% failed to meet both the U.S. and the FRG regulations. A larger percentage, 60%, would not conform to the new standard suggested in the United States, and more than 80% failed to comply with the even stricter Dutch standard.


Challenges faced by edentulous patients (EDPs) during complete denture prostheses (CDP) service delivery in Fiji - a qualitative study.
Edentulism is a state of having no teeth in the oral cavity, an irreversible condition popularly known as the marker of disease burden on the oral health. For edentulous patients (EDPs) Complete Denture Prostheses (CDP) is a means to improve oral health. Due to limited studies in this area, this research aimed to explore the challenges faced by the EDPs during CDP service delivery in Fiji. A directed descriptive qualitative study was conducted among EDPs attending Dental Prosthetic Clinics (DPCs) at the four centres in Fiji under purposive sampling. A semi-structured questionnaire with open ended questions was used for in-depth interview with EDPs who had worn CDP for 1 year via telephone. Participant responses were recorded, transcribed verbatim and analyzed manually using thematic analysis. A total of 30 EDPs participated in the study. Six themes were identified as challenges faced by the EDPs during CDP service delivery in Fiji: lack of information, non-compliance, overwhelmed by illness, reduction on quality of life (QoL) financial barriers to CDP treatment care and personal acceptance. 77% of EDPs felt they did not receive adequate information on CDP when attending DPCs which indicated the non-compliance nature irrespective of using and cleaning CDP on a daily basis. The Dental Professionals (DPs) at the DPCs gave their full support in attending to the CDP challenges faced by the EDPs in Fiji during the review clinics. The EDPs expressed a variety of challenges that was faced while seeking appropriate CDP services in Fiji. The findings demonstrate the need to explore approaches to develop patients' engagement practices during CDP service delivery by the Dental professionals (DPs), which leads to effective oral health promotion in Fiji for CDP wearers.


Egg and larval load assessment and its influence on oviposition behaviour of the leaf beetle Galerucella nymphaeae.
The oviposition behaviour of the water-lily beetle Galerucella nymphaeae was examined. This species is a specialist herbivore on the floating leaves of nymphaeids Nymphaeaceae and especially on the yellow water-lily, Nuphar lutea. Females lay their eggs in clutches on the leaves, and after hatching, the larvae feed on the leaves. The quality of the leaves decreases quickly after the larvae hatch, and eventually the leaves will sink below the water surface, whereupon the eggs, 1st-instar larvae and pupae are killed by drowning. The influence of conspecific eggs, larvae and feeding tracks on the oviposition preferences of the beetles was tested. Females were allowed to choose between fresh leaves and leaves with conspecific eggs and larvae as well as between leaves with larvae and leaves with feeding tracks but no larvae. An attempt was also made to determine whether eggs and larvae affect the oviposition rate of females when they are not given the opportunity to oviposit on untouched leaves. The results indicate that females tended to avoid leaves with conspecific larvae or to exhibit a decreased oviposition rate on such leaves. Females also avoided conspecific eggs, although the oviposition rate was not influenced by the presence of conspecific eggs. When females were allowed to choose between leaves with larvae and leaves with feeding tracks, possible discrimination against leaves with larvae just fails to reach the 5% level.


A high-throughput study of visceral organs in CT-scanned pigs.
It has been debated whether intensive selection for growth and carcass yield in pig breeding programmes can affect the size of internal organs, and thereby reduce the animal's ability to handle stress and increase the risk of sudden deaths. To explore the respiratory and circulatory system in pigs, a deep learning based computational pipeline was built to extract the size of lungs and hearts from CT-scan images. This pipeline was applied on CT images from 11,000 boar selection candidates acquired during the last decade. Further, heart and lung volumes were analysed genetically and correlated with production traits. Both heart and lung volumes were heritable, with h2 estimated to 0.35 and 0.34, respectively, in Landrace, and 0.28 and 0.4 in Duroc. Both volumes were positively correlated with lean meat percentage, and lung volume was negatively genetically correlated with growth (rg = - 0.48 ± 0.07 for Landrace and rg = - 0.44 ± 0.07 for Duroc). The main findings suggest that the current pig breeding programs could, as an indirect response to selection, affect the size of hearts- and lungs. The presented methods can be used to monitor the development of internal organs in the future.


KRAS mutation effects on the 2-[18F]FDG PET uptake of colorectal adenocarcinoma metastases in the liver.
Deriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regard to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM). 2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of 37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in different commercially available software packages. PET standard uptake values (SUV) were corrected for: (1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter and (2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak and maximum SUV were investigated using Student's t test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis. These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SURMEAN, SURPEAK and SURMAX, respectively. Fifteen patients harbored KRAS missense mutations (KRAS+), while another 3 harbored KRAS gene amplification. For 31 lesions, the mutational status was derived from the PET/CT-guided biopsy. The Student's t test p values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SURMAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve = 0.77 and 0.75 for the two different segmentations, respectively, with a mean specificity of 0.69 and sensitivity of 0.85. The correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.


Genetic associations of leisure sedentary behaviors and the risk of 15 site-specific cancers: A Mendelian randomization study.
Leisure sedentary behavior (LSB) is associated with the risk of cancer, but the causal relationship between them has not been clarified. The aim of this study was to assess the potential causal association between LSB and risk of 15 site-specific cancers. The causal association between LSB and cancer were assessed with univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR). 194 SNPs associated with LSB (from the UK Biobank 408,815 individuals) were adopted as the instrument variables. Sensitivity analyses were performed to ensure the robustness of the results. UVMR analysis revealed that television watching significantly increased the risk of endometrial cancer (OR = 1.29, 95% CI = 1.02-1.64, p = 0.04) (mainly the endometrioid histology [OR = 1.28, 95% CI = 1.02-1.60, p = 0.031]),breast cancer (OR = 1.16, 95% CI = 1.04-1.30, p = 0.007) (both ER+ breast cancer [OR = 1.17, 95% CI = 1.03-1.33, p = 0.015], and ER- breast cancer [OR = 1.55, 95% CI = 1.26-1.89, p = 2.23 × 10-5 ]). Although causal association was not found between television watching and ovarian cancer, it was seen in low grade and low malignant potential serous ovarian cancer (OR = 1.49, 95% CI = 1.07-2.08, p = 0.018). However, significant results were not obtained in the UVMR analysis between driving, computer use and the 15 types of cancer. Further MVMR analysis indicated that the above results are independent from most metabolic factors and dietary habits, but mediated by educational attainment. LSB in form of television watching has independent causal association with the risk of endometrial cancer, breast cancer, and ovarian cancer.


Effect of 15° Reverse Trendelenburg Position on Arterial Oxygen Tension during Isoflurane Anesthesia in Horses.
Lower than expected arterial oxygen tension (PaO2) continues to be an unresolved problem in equine anesthesia. The aim of this randomized, crossover, and prospective study using six adult horses is to determine if a 15° reverse Trendelenburg position (RTP) increases PaO2 during inhalation anesthesia. Under constant-dose isoflurane anesthesia, dorsally recumbent horses were positioned either horizontally (HP) or in a 15° RTP for 2 h. Lungs were mechanically ventilated (15 mL/kg, 6 breaths/min). Arterial carbon dioxide tension (PaCO2), PaO2, inspired oxygen fraction (FiO2), and end-tidal carbon dioxide tension (EtCO2) were determined every 30 min during anesthesia. Indices of dead-space ventilation (Vd/Vt), oxygenation (P-F ratio), and perfusion (F-shunt) were calculated. Dobutamine and phenylephrine were used to support mean arterial pressure (MAP). Data are presented as median and range. In one horse, which was deemed an outlier due to its thoracic dimensions and body conformation, indices of oxygenation worsened in RTP compared to HP (median PaO2 438 vs. 568 mmHg; P-F ratio 454 vs. 586 mmHg, and F-shunt 13.0 vs. 5.7 mmHg). This horse was excluded from calculations. In the remaining five horses they were significantly better with RTP compared to HP. Results in remaining five horses showed that PaO2 (502, 467-575 vs. 437, 395-445 mmHg), P-F ratio (518, 484-598 vs. 455, 407-458 mmHg), and F-shunt (10.1, 4.2-11.7 vs. 14.2, 13.8-16.0 mmHg) were significantly different between RTP and HP (p = 0.03). Other variables were not significantly different. In conclusion, the 15° RTP resulted in better oxygenation than HP in dorsally recumbent, isoflurane-anesthetized horses, although worsening of oxygenation may occur in individual horses. A study detailing the cardiovascular consequences of RTP is necessary before it can be recommended for clinical practice.


Glial tumors of the retina. The 2009 King Khaled Memorial Lecture.
Retinal glial tumors and pseudotumors can be classified into astrocytic hamartoma, acquired retinal astrocytoma, massive gliosis, and focal nodular gliosis. Each has different clinical manifestations. Astrocytic hamartoma is usually seen patients who have some manifestations of tuberous sclerosis complex (TSC). It can occur as a noncalcified or calcified variety, and often a combination of the two, and has fairly typical features with fluorescein angiography, ultrasonography, and optical coherence tomography. Although it is generally a stationary lesion, an aggressive variant seen in very young children with TSC can lead to exudative retinopathy, retinal detachment, and neovascular glaucoma. Acquired astrocytoma general occurs in somewhat older individuals who do not have TSC. Like the aggressive form of astrocytic hamartoma it can lead to exudative retinopathy and exudative retinal detachment. Pseudoneoplastic diffuse retinal gliosis can occur as massive glial proliferation in eyes with prior trauma, Coats disease, retinal angiomatosis and other conditions and often occurs in blind eyes. Pseudoneoplastic focal retinal gliosis is characterized by a very superficial, white, noncalcified lesion in otherwise normal eye in somewhat older individuals. Recognition of these glial lesions is important because they can resemble malignant tumors and have different clinical courses and complications.


Maternal High-Fat Diet Multigenerationally Impairs Hippocampal Synaptic Plasticity and Memory in Male Rat Offspring.
As advances are made in the field of developmental origins of health and disease, there is an emphasis on long-term influence of maternal environmental factors on offspring health. Maternal high-fat diet (HFD) consumption has been suggested to exert detrimental effects on cognitive function in offspring, but whether HFD-dependent brain remodeling can be transmitted to the next generations is still unclear. This study tested the hypothesis that HFD consumption during rat pregnancy and lactation multigenerationally influences male offspring hippocampal synaptic plasticity and cognitive function. We observed that hippocampus-dependent learning and memory was impaired in 3 generations from HFD-fed maternal ancestors (referred as F1-F3), as assessed by novel object recognition and Morris water maze tests. Moreover, maternal HFD exposure also affected electrophysiological and ultrastructure measures of hippocampal synaptic plasticity across generations. We observed that intranasal insulin replacement partially rescued hippocampal synaptic plasticity and cognitive deficits in F3 rats, suggesting central insulin resistance may play an important role in maternal diet-induced neuroplasticity impairment. Furthermore, maternal HFD exposure enhanced the palmitoylation of GluA1 critically involved in long-term potentiation induction, while palmitoylation inhibitor 2-bromopalmitate counteracts GluA1 hyperpalmitoylation and partially abolishes the detrimental effects of maternal diet on learning and memory in F3 offspring. Importantly, maternal HFD-dependent GluA1 hyperpalmitoylation was reversed by insulin replacement. Taken together, our data suggest that maternal HFD exposure multigenerationally influences adult male offspring hippocampal synaptic plasticity and cognitive performance, and central insulin resistance may serve as the cross-talk between maternal diet and cognitive impairment across generations.


Higher order structure of chromatin: orientation of nucleosomes within the 30 nm chromatin solenoid is independent of species and spacer length.
We have used electric dichroism to study the arrangement of nucleosomes in 30 nm chromatin solenoidal fibers prepared from a variety of sources (CHO cells, HeLa cells, rat liver, chicken erythrocytes, and sea urchin sperm) in which the nucleosome spacer length varies from approximately 10 to approximately 80 bp. Field-free relaxation times are consistent only with structures containing 6 +/- 1 nucleosomes for every 11 nm of solenoidal length. With very few assumptions about the arrangement of the spacer DNA, our dichroism data are consistent with the same orientation of the chromatosomes for every chromatin sample examined. This orientation, which maintains the faces of the radially arranged chromatosomes inclined at an angle between 20 degrees-33 degrees to the solenoid axis, thus appears to be a general structural feature of the higher order chromatin fiber.


Intermodality feature fusion combining unenhanced computed tomography and ferumoxytol-enhanced magnetic resonance angiography for patient-specific vascular mapping in renal impairment.
The purpose of this study was to establish the feasibility of fusing complementary, high-contrast features from unenhanced computed tomography (CT) and ferumoxytol-enhanced magnetic resonance angiography (FE-MRA) for preprocedural vascular mapping in patients with renal impairment. In this Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, 15 consecutive patients underwent both FE-MRA and unenhanced CT scanning, and the complementary high-contrast features from both modalities were fused to form an integrated, multifeature image. Source images from CT and MRA were segmented and registered. To validate the accuracy, precision, and concordance of fused images to source images, unambiguous landmarks, such as wires from implantable medical devices or indwelling catheters, were marked on three-dimensional (3D) models of the respective modalities, followed by rigid co-registration, interactive fusion, and fine adjustment. We then compared the positional offsets using pacing wires or catheters in the source FE-MRA (defined as points of interest [POIs]) and fused images (n = 5 patients, n = 247 points). Points within 3D image space were referenced to the respective modalities: x (right-left), y (anterior-posterior), and z (cranial-caudal). The respective 3D orthogonal reference axes from both image sets were aligned, such that with perfect registration, a given point would have the same (x, y, z) component values in both sets. The 3D offsets (Δx mm, Δy mm, Δz mm) for each of the corresponding POIs represent nonconcordance between the source FE-MRA and fused images. The offsets were compared using concordance correlation coefficients. Interobserver agreement was assessed using intraclass correlation coefficients and Bland-Altman analyses. Thirteen patients (aged 76 ± 12 years; seven female) with aortic valve stenosis and chronic kidney disease and two patients with thoracoabdominal vascular aneurysms and chronic kidney disease underwent FE-MRA for preprocedural vascular assessment, and unenhanced CT examinations were available in all patients. No ferumoxytol-related adverse events occurred. There were 247 matched POIs evaluated on the source FE-MRA and fused images. In patients with implantable medical devices, the mean offsets in spatial position were 0.31 ± 0.51 mm (ρ = 0.99; Cb = 1; 95% confidence interval [CI], 0.99-0.99) for Δx, 0.27 ± 0.69 mm (ρ = 0.99; Cb = 0.99; 95% CI, 0.99-0.99) for Δy, and 0.20 ± 0.59 mm (ρ = 1; Cb = 1; 95% CI, 0.99-1.00) for Δz. Interobserver agreement was excellent (intraclass correlation coefficient, >0.99). The mean difference in offset between readers was 1.5 mm. Accurate 3D feature fusion is feasible, combining luminal information from FE-MRA with vessel wall information on unenhanced CT. This framework holds promise for combining the complementary strengths of magnetic resonance imaging and CT to generate information-rich, multifeature composite vascular images while avoiding the respective risks and limitations of both modalities.


[Corrigendum] miR‑382 inhibits breast cancer progression and metastasis by affecting the M2 polarization of tumor‑associated macrophages by targeting PGC‑1α.
Subsequently to the publication of the above article, the authors have contacted the Editorial Office to explain that Fig. 7 was published containing an erroneously placed data panel. Specifically, the center panel of the images selected for the invasion assay experiments portrayed in Fig. 7A (i.e., the miR‑382 experiment) was chosen incorrectly, and the authors have requested that this panel be replaced by the panel containing the data that was actually used for the statistical analysis shown in part (B). The revised version of Fig. 7, showing the correct data panel for the miR‑382 experiment in the invasion assay images in part (A), is shown on the next page. The authors can confirm that the change made to this figure does not affect the overall conclusions reported in the study, and all the authors agree to the publication of this corrigendum. The authors are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this additional Corrigendum; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [International Journal of Oncology 61: 126, 2022; DOI: 10.3892/ijo.2022.5416].


Active disturbance rejection control for nanopositioning: A robust U-model approach.
Hysteresis severely reduces positioning performance of a piezoelectric nanopositioning stage. Linear active disturbance rejection control (LADRC) is a practical solution to improve the positioning accuracy. However, the PD controller utilized in the LADRC is not effective enough to suppress the uncancelled total disturbance, and high-order pure integrators are difficult to be stabilized just by a PD controller. In this work, a robust U-model active disturbance rejection control (RUADRC) is proposed by incorporating the core idea of the U-model control and the Glover-McFarlane control. Then, the controlled plant can be dynamically transformed to a unit. Difficulties in stabilizing high-order pure integrators are decreased, the phase lag between the input and output of a controlled plant is reduced, and the closed-loop responses is sped up. In addition, the influence of both inaccurate total disturbance estimation and imperfect approximation is also minimized by the Glover-McFarlane control Closed-loop stability, steady-state tracking error, and the phase advantage of the RUADRC have been analysed. Theoretical results show that the RUADRC promises a timelier and more accurate positioning. Experimental results still confirm the advantages of the RUADRC over the LADRC on both reference tracking speed, accuracy and disturbance rejection ability.


Adult recollections of a formerly autistic child.
The life history, current status, and memories of a 31-year-old man who, as a child, had been diagnosed as autistic by Kanner and others is described. Prognostic criteria as related to this individual's outcome are discussed. Some speculations about the inner life of autistic children are advanced on the basis of his recollections. Finally, some hypotheses for further research are suggested on the basis of information gained from this case review.


Endogenous serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) levels in large regions and in discrete brain areas of C57BL and BALBc mice at three times of the day.
The serotoninergic system has been analysed in the brainstem and the forebrain of adult C57BL and BALBc mice. Endogenous 5-HT and 5-HIAA levels have also been measured in the different raphe nuclei and in the caudate nucleus and the hippocampus of these strains, using the micropunch technique and the radioenzymatic method (for 5-HT) and a new radioimmunoassay (for 5-HIAA). This investigation was performed at three times of the day: 9:00 hr; 14:00 hr; 20:00 hr to underline the differences between the strains. Most of the time, higher 5-HT and 5-HIAA levels are found in the brainstem and the raphe nuclei of the BALBc strain compared to C57BL. In the forebrain the differences are reversed, except in the caudate nucleus and the hippocampus where the levels of 5-HT are identical in the two strains. Moreover the 5-HIAA/5-HT ratio shows a higher turn-over of the amine in the C57BL strain.


Use of a novel computerized decision aid for aneuploidy screening: a randomized controlled trial.
To assess whether knowledge following use of a decision aid (DA) for aneuploidy screening and testing is inferior to knowledge in women who saw a genetic counselor (GC) only. This is a randomized controlled noninferiority trial of pregnant women at ≤22 weeks. Women who were scheduled for GC were randomly allocated to use a DA before GC or to GC alone. The primary outcome was knowledge score, comparing women who had used the DA only to those who saw GC alone. Analysis was by intent to treat. Between January and October 2017, 197 women were randomized, 105 to GC only and 92 to DA use before GC. Demographics and baseline knowledge were similar between groups. Mean knowledge score following DA use was not inferior to mean knowledge score following GC only (10.4 vs. 10.6, p = 0.306). Decisional conflict was similar following completion of the DA to following GC only, but was reduced following completion of both the DA and GC compared with GC only (0.22 vs. 1.74, p = 0.003). Knowledge surrounding aneuploidy screening in women who used a DA was not inferior to knowledge in women who underwent GC. Use of the DA in addition to GC reduced decisional conflict.


Concentrations and sources of cadmium, copper, lead and zinc in house dust in Christchurch, New Zealand.
The amounts (microgram m-2) and concentrations (microgram g-1) of cadmium, copper, lead and zinc have been measured in house dust in Christchurch, New Zealand. For 120 houses surveyed the geometric mean concentrations of the four metals are 4.24 micrograms g-1, 165 micrograms g-1, 573 micrograms g-1 and 10,400 micrograms g-1, respectively. In addition eleven variables, such as house age, carpet wear and traffic density, were recorded for each property and the results analysed with respect to their effects on the amounts and concentrations of the four elements. The amounts of all the metals were highly correlated with the overall dustiness of the houses, which was found to be predominantly determined by the degree of carpet wear. No one dominant source of cadmium was identified, although several minor sources including carpet wear, galvanized iron roofs and red/orange/yellow coloured carpets were implicated. Petrol lead and lead-based paints were identified as significant sources of lead in house dust. Rubber carpet underlays or backings were identified as a significant source of zinc, with some contribution from galvanized iron roofs. Road traffic and probably the existence of a fire place appear to contribute to the copper levels.


Rosette formation in chronic lymphocytic leukemia: studies of lymphocytes from peripheral blood and lymph node biopsy.
Lymphocytes were obtained from a lymph node biopsy from a patient with chronic lymphocytic leukemia in whom B and T lymphocytes were present in equal percentages in the peripheral blood. The lymphocytes were examined for rosette formation with mouse and sheep erythrocytes in order to determine whether the leukemic process was of the B or T cell type.


Surya Namaskar: As an Alternative for Aerobic Fitness.
"Surya Namaskar" (SN) may be used as a need-based short-duration aerobic activity in a confined space to establish as a substitute of an equivalent routine physical training in challenging stressful conditions. Noninvasive oxygen-kinetics metabolic responses between SN and endurance work on bicycle ergometry (BE) were compared across different phases of maximal oxygen uptake percentage (%VO2 max). SN, comprising three complete rounds per min (36 beats/min of a metronome; SN consists of 12 poses per round), was performed rhythmically and continuously for 5 min to simulate an incremental BE test (25 watts/2 min at 60 rpm). SN results in a significant (P < 0.05) greater increase of arteriovenous oxygen difference at 71%-80% VO2 max while keeping a low respiratory exchange ratio (P < 0.01 and 0.001) at 41%-80% VO2 max exercising state. SN could be an ideal form of aerobic exercise instead of BE.


[Infiltrating lobular breast cancer: histological and immunohistochemical characteristics].
Lobular carcinoma ranks second among most frequent tumors of the breast. Metastases to the lymph nodes and distant organs are one of the most important prognostic factors. 60% regional lymph node metastases were morphologically diagnosed during surgical removal of the tumor. Distant metastases rate was 1% at the beginning of the treatment and reached 10% within 5-year follow-up. Cases of secondary uterus and epiploon lobular carcinoma are rare and tumor location in the breast should be proved.


Characterization of host lymphoid cells in antibody-facilitated bone marrow chimeras.
We have produced stable murine antibody-facilitated (AF) chimeras by the simultaneous injection of P1 bone marrow cells and anti-P2 monoclonal antibody into normal (unirradiated) adult (P1 X P2)F1 recipients. These AF chimeras are healthy, long-lived, and exhibit no overt signs of graft-versus-host disease. They are immunocompetent and tolerant of host, P2-encoded alloantigens. Donor cell engraftment and takeover, monitored by glucosephosphate isomerase isozyme patterns, is usually complete (greater than 95%) in the peripheral blood, bone marrow, and hemopoietic stem cell compartments of long-term (greater than 3 months posttransplantation) AF chimeras. We report here, however, that splenic, lymph node, and thymic leukocytes of AF chimeras represent donor/host chimeric populations. Spleen cell populations of AF chimeras exhibit substantial chimera-to-chimera variation in the preponderant residual host cell type(s) present. Our interpretations of the implications of these findings are discussed.


Stratification in the gallbladder during intravenous cholangiography.
The stratification (layering) phenomenon in the gallbladder is a source of errors in interpretation of intravenous cholangiography. It may mimic stones that do not exist or conceal stones that do. To avoid false-positive or false-negative interpretations, it is suggested that delayed films be taken at 4 hours in cases which demonstrate a layering phenomenon. By this time, a normal gallbladder will be homogeneously opacified and a diseased one will reveal its stones. Horizontal beam roentgenograms are mandatory for complete evaluation.


Perceptions and expectations of adults with type 1 diabetes for the use of artificial pancreas systems with and without glucagon addition: Results of an online survey.
The first hybrid artificial pancreas (AP) systems with insulin only (mono-hormonal) have recently reached the market while next generations systems are under development including those with glucagon addition (bi-hormonal). Understanding the expectations and impressions of future potential users about AP systems is important for optimal use of this clinically effective emerging technology. An online survey about AP systems which consisted of 50 questions was addressed to people with type 1 diabetes in the province of Quebec, Canada. Surveys were completed by 123 respondents with type 1 diabetes (54% women, mean (SD) age 40.2 (14.4) y.o., diabetes duration 23.7 (14.1) years, 58% insulin pump users and 43% glucose sensor users). Of the respondents, 91% understood how AP systems work, 79% trusted them with correct insulin dosing, 73% were willing to replace their current treatment with AP and 80% expected improvement in quality of life. Anxiety about letting an algorithm control their glucose levels was expressed by 18% while the option of ignoring or modifying AP instructions was favoured by 88%. As for bi-hormonal AP systems, 83% of respondents thought they would be useful to further reduce hypoglycemic risks. Overall, respondents expressed positive views about AP systems use and high expectations for a better quality of life, glycemic control and hypoglycemia reduction. Data from this survey could be useful to health care professionals and developers of AP systems.


Cyclooxygenase-2 in newborn hyperoxic lung injury.
Supraphysiological O2 concentrations, mechanical ventilation, and inflammation significantly contribute to the development of bronchopulmonary dysplasia (BPD).Exposure of newborn mice to hyperoxia causes inflammation and impaired alveolarization similar to that seen in infants with BPD.Previously, we demonstrated that pulmonary cyclooxygenase-2 (COX-2) protein expression is increased in hyperoxia-exposed newborn mice.The present studies were designed to define the role of COX-2 in newborn hyperoxic lung injury.We tested the hypothesis that attenuation of COX-2 activity would reduce hyperoxia-induced inflammation and improve alveolarization.Newborn C3H/HeN micewere injected daily with vehicle, aspirin (nonselective COX-2 inhibitor), or celecoxib (selective COX-2 inhibitor) for the first 7 days of life.Additional studies utilized wild-type (C57Bl/6, COX-2(+/+)), heterozygous (COX-2(+/-)), and homozygous (COX-2(-/-)) transgenic mice.Micewere exposed to room air (21% O2) or hyperoxia (85% O2) for 14 days.Aspirin-injected and COX-2(-/-) pups had reduced levels of monocyte chemoattractant protein (MCP-1) in bronchoalveolar lavage fluid (BAL).Both aspirin and celecoxib treatment reduced macrophage numbers in the alveolar walls and air spaces.Aspirin and celecoxib treatment attenuated hyperoxia-induced COX activity, including altered levels of prostaglandin (PG)D2 metabolites.Decreased COX activity, however, did not prevent hyperoxia-induced lung developmental deficits.Our data suggest thatincreased COX-2 activity may contribute to proinflammatory responses, including macrophage chemotaxis, during exposure to hyperoxia.Modulation of COX-2 activity may be a useful therapeutic target to limit hyperoxia-induced inflammation in preterm infants at risk of developing BPD.


Molecular Iron Oxide Clusters Boost the Oxygen Reduction Reaction of Platinum Electrocatalysts at Near-Neutral pH.
The oxygen reduction reaction (ORR) is a key energy conversion process, which is critical for the efficient operation of fuel cells and metal-air batteries. Here, we report the significant enhancement of the ORR-performance of commercial platinum-on-carbon electrocatalysts when operated in aqueous electrolyte solutions (pH 5.6), containing the polyoxoanion [Fe28 (μ3 -O)8 (L-(-)-tart)16 (CH3 COO)24 ]20- . Mechanistic studies provide initial insights into the performance-improving role of the iron oxide cluster during ORR. Technological deployment of the system is demonstrated by incorporation into a direct formate microfluidic fuel cell (DFMFC), where major performance increases are observed when compared with reference electrolytes. The study provides the first examples of iron oxide clusters in electrochemical energy conversion and storage.


Relationship of asymptomatic bacteriuria and renal scarring in children with neuropathic bladders who are practicing clean intermittent catheterization.
To determine whether untreated asymptomatic bacteriuria is associated with renal scarring in children with neuropathic bladders managed with clean intermittent catheterization (CIC). Retrospective study of 207 patients aged 1 to 30 years (mean 11.9 +/- 5.5 years) treated with CIC for a mean duration of 6.6 +/- 3.9 years by the spina bifida program at Children's National Medical Center. All patients were examined for renal scarring with dimercaptosuccinic acid (DMSA) renal scans. Catheterized urine cultures were obtained annually, but bacteriuria ( > 10,000 colony-forming units of a single organism per milliliter) was treated only if the patients had symptoms or if vesicoureteral reflux (VUR) was present. Of 207 children, 176 (85%) had one or more episodes of untreated asymptomatic bacteriuria and 72 (35%) had one or more febrile episodes associated with positive urine culture results. Biannual DMSA scans detected 54 new scarring episodes in 42 patients. Of newly recognized scars, 55% were preceded within 1 year by a febrile infection, 26% were detected in patients with VUR and asymptomatic bacteriuria, and 19% were detected in new patients during their initial examination. Univariate analysis revealed that new scarring was present in 35 of 176 patients with asymptomatic bacteriuria compared with 7 of 31 patients without (p = 809). Logistic regression analysis revealed that factors associated with scarring were febrile infections (adjusted odds ratio [OR] = 30.6, 95% confidence interval [CI] = 9.8 to 95.8), age more than 20 years (OR = 4.3, CI = 1.01 to 18.5), the presence of bladder trabeculation (OR = 2.7, CI = 1.0 to 7.6), and VUR (OR = 58.8, CI = 6.3 to 547.3), but asymptomatic bacteriuria was not associated with scarring. In the absence of VUR, asymptomatic bacteriuria in patients undergoing CIC is not a significant risk factor for scarring and does not require antibiotic therapy.


Prostatic aspiration biopsy: an assessment of accuracy based on long-term observations.
We present the results of transrectal thin needle aspiration biopsy of the prostate in 133 patients. Test specificity was 94 per cent and sensitivity also appeared to be high initially. However, with repeated rectal examinations and biopsies during an 11-year period a number of additional false negatives became apparent, which resulted in an apparent test sensitivity of 82 per cent, lower than most previously published reports. Our data suggest that aspiration biopsy has specificity and sensitivity similar to core biopsy, it is important to re-test patients who have a palpable abnormality and an initially benign biopsy, and aspiration biopsy simplicity allows for a low threshold of suspicion of subtle abnormalities and for repeating biopsies after negative findings.


Phase I dose-escalation study of stereotactic body radiotherapy (SBRT) for poor surgical candidates with localized renal cell carcinoma.
To evaluate the tolerability of escalating doses of stereotactic body radiotherapy (SBRT) for primary treatment of localized renal cell carcinoma (RCC) in poor surgical candidates. Eligible patients included those with clinically staged radiographic and or pathologically confirmed RCC who had not undergone previous abdominal or pelvic radiotherapy. All patients had comorbid medical conditions which precluded surgery. Median (range) patient age was 77.6years (range 59-89) years and all patients had Karnofsky Performance Status of ⩾60. Median tumor volume was 57.9cm(3) (range 13.8-174.7cm(3)). Dose-limiting toxicity (DLT) was defined as grade 3 or worse gastrointestinal/genitourinary toxicity by Common Terminology Criteria of Adverse Events (version 4). Tumor response was assessed by imaging results using Response Evaluation Criteria In Solid Tumors (RECIST) measurement and percutaneous biopsy. A total of 19 patients (13 men and 6 women) were treated on protocol from June 2006 through August 2011. Groups of 3-6 patients received 24, 32, 40, and 48Gy in 4 fractions. Median (range) follow-up was 13. 7months (5.9-34.7months). For possibly treatment-related acute toxicities, one patient developed grade 2 fatigue and one developed grade 4 duodenal ulcer. For possibly treatment-related late toxicities, 2 patients experienced grade 3 renal toxicity (worsening chronic kidney disease), one reported grade 2 urinary incontinence and one developed grade 4 duodenal ulcer. Among the 15 patients with evaluable response, 3 and 12 had partial response and stable disease, respectively, utilizing RECIST criteria. Among the 11 patients who had post-SBRT biopsy, only one (9%) was negative on first biopsy and an additional one (9%) turned negative without further therapy on second biopsy. Dose escalation to 48Gy in 4 fractions has been achieved successfully without dose-limiting toxicities. A planned extension of this phase I trial is currently underway treating patients to 60Gy in 3 fractions to further evaluate this experimental therapy.


Nitrofurazone-induced DNA damage to tissues of mice.
Cytotoxicity and DNA damage by nitrofurans has previously been correlated with metabolic reduction of these drugs in vitro. In the present study, nitrofurazone increased the rate of disappearance of stable [3H]thymidine labelled DNA from tissues of mice fed 0.1% nitrofurazone in the diet. Significant loss of labelled DNA occurred within 25 days after the start of the diet in all tissue observed, and loss was in relation to the rate of metabolic reduction of nitrofurazone. A similar correlation was found when another endpoint for DNA damage was used; nitrofurazone reduced by mouse tissue slices caused DNA single-strand breaks in cultured mouse L cells incubated in vitro with the tissues. Again, the ability of each tissue to produce toxic nitrofurazone metabolites determined the amount of DNA damage to the L cells.


Self-assembled chitosan derived microparticles inhibit tumor angiogenesis and induce apoptosis in Ehrlich-ascites-tumor bearing mice.
Self-assembled microparticles from chitosan (SAMC) was prepared by depolymerization induced by potassium persulfate. Particle size distribution data showed averaged around 5 μm size and SEM indicated the sequential formation of "RBC" shaped particles. Soluble SAMC consists of 'deacetylated' residues as revealed by 13C NMR. SAMC showed antitumor efficacy in human breast cancer cell lines through mitigation in cell proliferation, colony formation and cell migration. Anti-tumor and anti-angiogenic properties of SAMC was found in vivo Ehrlich ascites tumor (EAT) bearing mice model resulting in tumor growth inhibition (EAT control, 17.4 ml; SAMC treated, 6.8 ml) and improved survival potency (15 days). Moreover, the decrease in ascites VEGF secretion (EAT control, 1354 ng; SAMC treated, 351 ng) accompanied with reduction in neovessel formation. Apoptosis induction by SAMC was confirmed by DNA fragmentation, caspase activities and fluorescence staining methods respectively. SAMC may be a safe candidate for anti-tumor dietary supplement production in food industry.


Cerebral glycosidases in experimental Creutzfeldt-Jakob disease.
In Creutzfeldt-Jakob disease (CJD), there are prominent ultrastructural alterations of the plasma membrane, which contains many glycolipids and glycoproteins. Glycosidases can degrade glycolipids and glycoproteins. Gangliosides, a subset of glycolipids, are decreased in amount at the terminal stages of CJD, and CJD infectivity is closely associated with membrane rich fractions. We therefore studied 10 glycosidases, and found a statistically significant increase in beta-xylosidase, beta-glucuronidase, N-acetyl-beta-D-glucosaminidase and N-acetyl-beta-D-galactosaminidase activities in CJD. In contrast, alpha-glucosidase, beta-glucosidase, alpha-galactosidase, alpha-mannosidase, alpha-fucosidase, and beta-galactosidase were not significantly changed. The above results are consistent with degenerative membrane changes observed morphologically, and with increased degradation of sugar residues on lipids and/or proteins. These changes may be effected by the accumulation of the CJD agent in cell membranes. We suggest that the higher activities of these enzymes in CJD may be partially responsible for some of the structural and biochemical alterations in CJD infected brains.


Response to bidirectional and reverse selection for mating behavior in Japanese quail Coturnix coturnix japonica.
Reported is a genetic analysis of mating behavior in male Japanese quail. Data were obtained from replicated experiments involving 12 generations of divergent selection for high and low cumulative number of completed matings (CNCM). No trait measured in the randombred control population changed significantly over time. Asymmetrical responses between the divergent lines were observed during various phases of selection. Reversed selection showed that additive genetic variance remains in the high lines. Small and unimportant were drift and error variances. Genetic and phenotypic relationships between CNCM and body weight were small but positive, while those between CNCM and relative aggressiveness were positive and intermediate. Also positive and intermediate were the correlations between CNCM and cloacal gland size.


Comparison of muscle volume between congenital and acquired superior oblique palsies by magnetic resonance imaging.
Magnetic resonance imaging (MRI) studies of superior oblique (SO) muscles have revealed a high incidence of SO muscle atrophy/hypoplasia in congenital SO palsy patients. It has also been reported that long-standing acquired SO palsy patients show atrophic SO muscles in the affected eye. The purpose of this study was to compare the incidence of SO muscle atrophy/hypoplasia in congenital and acquired SO palsy by utilizing MRI. Coronal MRI image planes were taken from 29 cases of unilateral congenital SO palsy and 9 cases of acquired unilateral SO palsy patients. The SO muscle bellies were traced and their sizes were measured from each image plane. The total volume of the affected superior oblique muscle was compared with that of the normal fellow eye. The mean volume of the affected superior oblique muscle to that of the normal muscle was 45.3% (SD = 30.1) in the congenital group and 65.8% (SD = 22.7) in the acquired group. The volume reduction of the SO muscle in congenital SO palsy patients appears to be mainly a congenital abnormality rather than a secondary change, as seen in acquired SO palsy patients.


Study protocol of transcranial electrical stimulation at alpha frequency applied during rehabilitation: A randomized controlled trial in chronic stroke patients with visuospatial neglect.
A frequent post stroke disorder in lateralized attention is visuospatial neglect (VSN). As VSN has a strong negative impact on recovery in general and independence during daily life, optimal treatment is deemed urgent. Next to traditional stroke treatment, non-invasive brain stimulation offers the potential to facilitate stroke recovery as a complementary approach. In the present study, visual scanning training (VST; the current conventional treatment) will be combined with transcranial alternating current stimulation (tACS) to evaluate the additive effects of repeated sessions of tACS in combination with six-weeks VST rehabilitation. In this double-blind randomized placebo-controlled intervention study (RCT), we will compare the effects of active tACS plus VST to sham (placebo) tACS plus VST, both encompassing 18 VST training sessions, 40 minutes each, during 6 weeks. Chronic stroke patients with VSN (> 6 months post-stroke onset) are considered eligible for study participation. In total 22 patients are needed for the study. The primary outcome is change in performance on a cancellation task. Secondary outcomes are changes in performance on a visual detection task, two line bisection tasks, and three measures to assess changes in activities of daily living. Assessment is at baseline, directly after the first and ninth training session, after the last training session (post training), and 1 week and 3 months after termination of the training (follow-up). If effective, a tACS-VST rehabilitation program could be implemented as a treatment option for VSN. ClinicalTrials.gov ; registration number: NCT05466487; registration date: July 18, 2022 retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT05466487.


Elective drainage of the apical chest by posterior approach.
Pneumothorax due to incomplete reexpansion of remaining lung after a thoracic operation is difficult to drain via standard access routes. Apical chest drainage can be placed through a upper posterior point of the back, located in the laterovertebral area at the level of the first or second intercostal space. This technique, which is very safe and well tolerated, avoids the necessity to use thoracoplasty or muscle flap plombage of those residual cavities.


Efficacy of Three-Dimensional Endoscopy for Ventral Skull Base Pathology: A Systematic Review of the Literature.
The three-dimensional (3D) endoscope is a novel tool that provides stereoscopic vision and may allow for improved dexterity and safety during surgical resection of ventral skull base lesions. We describe here the cumulative experience available in the neurosurgical literature. A PubMed literature review was performed to identify and analyze all studies pertaining to 3D endoscopic endonasal skull base surgery. We identified 26 articles: 14 clinical articles, 5 simulated environment studies, 5 human cadaveric studies, and 2 expert opinions. In all the clinical studies, 262 patients were treated for the following 257 pathologies listed in the articles: 190 suprasellar/parasellar lesions (73.9%), 41 ventral skull base lesions (16.0%), 19 sinonasal pathologies (7.4%), and 7 cerebrospinal fluid leak repairs (2.7%). Complication rates, operative time, length of hospital stay, and extent of tumor resection were equivalent between two-dimensional (2D) and 3D endoscopy. However, all studies reported that subjective depth perception and spatial orientation were markedly improved with 3D technology. In 3 studies (11.5%), it was concluded that there was no clinically significant surgical benefit in switching from 2D to 3D endoscopy. All cadaveric studies and expert opinions concluded that 3D endoscopy improved the identification of key anatomical structures and was superior to 2D endoscopy. Simulated environment studies demonstrated that 3D endoscopy improved speed and accuracy of endonasal tasks, more so in novice surgeons. Our findings suggest that 3D endoscopy provides improved surgical dexterity by affording the surgeon with depth perception when manipulating tissue and maneuvering the endoscope in the endonasal corridor.


Investigation of the effects of transcranial alternating current stimulation (tACS) on self-paced rhythmic movements.
Human rhythmic movements spontaneously entrain to external rhythmic stimuli. Such sensory-motor entrainment can attract movements to different tempi and enhance their efficiency, with potential clinical applications for motor rehabilitation. Here we investigate whether entrainment of self-paced rhythmic movements can be induced via transcranial alternating current stimulation (tACS), which uses alternating currents to entrain spontaneous brain oscillations at specific frequencies. Participants swung a handheld pendulum at their preferred tempo with the right hand while tACS was applied over their left or right primary motor cortex at frequencies equal to their preferred tempo (Experiment 1) or in the alpha (10Hz) and beta (20Hz) ranges (Experiment 2). Given that entrainment generally occurs only if the frequency difference between two rhythms is small, stimulations were delivered at frequencies equal to participants' preferred movement tempo (≈1Hz) and ±12.5% in Experiment 1, and at 10Hz and 20Hz, and ±12.5% in Experiment 2. The comparison of participants' movement frequency, amplitude, variability, and phase synchrony with and without tACS failed to reveal entrainment or movement modifications across the two experiments. However, significant differences in stimulation-related side effects reported by participants were found between the two experiments, with phosphenes and burning sensations principally occurring in Experiment 2, and metallic tastes reported marginally more often in Experiment 1. Although other stimulation protocols may be effective, our results suggest that rhythmic movements such as pendulum swinging or locomotion that are low in goal-directedness and/or strongly driven by peripheral and mechanical constraints may not be susceptible to modulation by tACS.


A Comparative Study of Audiologic Outcomes for Two Transcutaneous Bone-Anchored Hearing Devices.
In 1977, Tjellstrom et al. used the concept of osseointegration and implanted patients with a titanium screw as part of the first bone-anchored hearing solution. Despite good hearing outcomes with the percutaneous device, there has been a drive for the development of transcutaneous bone conduction systems because of soft tissue complications, aesthetics, and loss or failure of the abutment. This study compares audiologic and quality of life questionnaire outcomes (author-designed questionnaire) for two transcutaneous bone conduction implants. Cross-sectional cohort study. Tertiary referral hospital and national audiology service. Twelve patients, 10 children and two adults. Six recipients of each device. Pure-tone audiometry, aided thresholds, speech discrimination scores, and quality of life questionnaire results. The unaided four-frequency average air conduction for affected ears was 60.8 dB HL for the Attract group and 57.8 dBHL for the Sophono group; these improved to mean aided thresholds of 30.6 dB HL and 29.8 dB HL, respectively. Therewas no statistical difference between the speech discrimination scores for the two devices in quiet at 55 dB SPL (p = 0.33) orin noise (p = 0.87). Both systems provide audiologic benefit compared with the unaided situation. Comparing small numbers of patients, there was no significant difference in aided thresholds or speech discrimination scores between these two transcutaneous bone-anchored implants. All Attract and Sophono users reported improvement in quality of life and would recommend their device to others in a similar situation.


Incorporating sex, gender and vulnerable populations in a large multisite health research programme: The Ontario Pharmacy Evidence Network as a case study.
Funders now frequently require that sex and gender be considered in research programmes, but provide little guidance about how this can be accomplished, especially in large research programmes. The purpose of this study is to present and evaluate a model for promoting sex- and gender-based analysis (SGBA) in a large health service research programme, the Ontario Pharmacy Evidence Network (OPEN). A mixed method study incorporating (1) team members' critical reflection, (2) surveys (n = 37) and interviews (n = 23) at programme midpoint, and (3) an end-of-study survey in 2016 with OPEN research project teams (n = 6). Incorporating gender and vulnerable populations (GVP) as a cross-cutting theme, with a dedicated team and resources to promote GVP research across the programme, was effective and well received. Team members felt their knowledge was improved, and the programme produced several sex- and gender-related research outputs. Not all resources were well used, however, and better communication of the purposes and roles of the team could increase effectiveness. The experience of OPEN suggests that dedicating resources for sex and gender research can be effective in promoting SGBA research, but that research programmes should also focus on communicating the importance of SGBA to their members.


Spatial patterns of mammalian brain aging: distribution of cathepsin D-immunoreactive cell bodies and dystrophic dendrites in aging dogs resembles that in Alzheimer's disease.
Elevated levels of the lysosomal enzyme cathepsin D are found in the early stages of Alzheimer's disease (AD) and co-occur with intraneuronal tangles. The present study tested whether increases in cathepsin D would emerge during aging in another mammalian species. Regional brain patterns of cathepsin D immunostaining were compared in dogs ages 0.35 to 16 years. Accumulations of immunopositive material were evident in neuronal cell bodies in many forebrain sites in middle-age to old dogs (>/=6 years). Three types could be distinguished: (1) dense aggregates with no particular position within the cell body; (2) crescent-shaped "caps" that occupied one pole of the cell body; and (3) very dense "spikes" that extended from the cell body for variable distances into the apical dendrite; these spikes were found in only a few areas, most notably the subiculum and layer V of neocortex. The spikes appeared between ages 2 and 5 years and increased steadily with age thereafter. Spikes were found in the subiculum in the aged human brain but only infrequently; they were, however, present in large numbers in AD brains. These results established that brain aging in dogs is (1) well advanced by middle age, (2) varies markedly across regions, and (3) in at least some of its aspects (dystrophic dendrites) is prominent in areas known to exhibit pathology early in the course of AD. Combined with previous results for rats, these findings indicated that changes in cathepsin D observed in AD, in particular in the temporal lobe, reflect a generalized mammalian pattern of brain aging.


Thin-layer chromatography of endotoxins, their derivatives and contaminants.
Thin-layer chromatographic (TLC) separation techniques were used to analyze the heterogeneity of various preparations which included smooth and rough endotoxins (ET), Lipid A precipitates and synthetic Lipid A samples and a novel cytotoxic bacterial lipid. Furthermore, carbohydrate-rich split products (PS) of ET were also separated on commercial silica-coated plates. Satisfactory results were obtained by two-dimensional TLC or by the combination of chromatography followed by high-voltage electrophoresis in the separation of PS of ET cleaved by mild acetic hydrolysis. Several spray reagents were found which were eminently suitable to detect carbohydrate containing compounds. Less specific but generally useful spray reagents were also developed which gave strong color reactions with lipids, proteinaceous and carbohydrate containing split products of the ET preparations. Improved chromatographic resolution has also revealed substantial heterogeneity in both rough and smooth ET samples. Three biological activities of the separated components could be determined. These were antigenicity detected by reactivity with monoclonal antibodies on the TLC plates, endotoxicity, determined by the Limulus amoebocyte lysate (LAL) test and direct cytotoxicity of P815 cells in vitro. Considerable amounts of non-endotoxic and non-antigenic contaminants could be detected in all preparations tested. Significant amounts of free Lipid A were also found in smooth ETs. Thus a new level of complexity is recognized by TLC within these preparations.


Differences in Cesarean section rates by fetal sex among Chinese women in the United States: Does Chinese culture play a role?
To investigate whether elements of Chinese culture, such as son preference, influence women's mode of child delivery, this paper analyzes how fetal sex affects C-section rates among Chinese mothers compared with Japanese mothers in the United States. It uses birth certificate data from 1990 to 2000, a period when women were routinely able to learn the sex of the fetus during pregnancy. Compared with Japanese mothers, Chinese mothers were 1 percentage point more likely to undergo C-section when giving birth to boys than when giving birth to girls. This result is robust to the addition of a rich set of controls and the restriction of the sample to infants without congenital diseases or anomalies at birth. The effects are concentrated in subgroups that are more likely to prefer sons-specifically, where both parents are Asian or where mothers are first-generation immigrants. The findings offer valuable insights for health professionals into culturally driven pregnancy behaviors among Chinese women, potentially enabling them to offer more culturally appropriate healthcare as they support women in making a healthy transition to motherhood.


Fragmentation studies on tetronasin by accurate-mass electrospray tandem mass spectrometry.
We report here the first full fragmentation study of tetronasin 1. Fragmentation was carried out by high-resolution ESI-CID-MS(n). The formulae of the fragment ions were determined by accurate mass measurements. It is demonstrated that the fragmentation routes observed derive essentially from a first loss of water via two different mechanisms. One minor route consists of a charge remote neutral loss and the second major route occurs via the formation of a carbocation. The fragments obtained from this carbocation were produced by subsequent complex neutral eliminations and the structures were inferred, in some cases, by carbocation stability.


Changes in corneal epithelial barrier function after excimer laser photorefractive keratectomy.
To use fluorophotometry to measure corneal epithelial barrier function after excimer laser photorefractive keratectomy (PRK). Seoul National University Hospital, Seoul, Korea. Twenty-five eyes of 21 patients (13 women, 8 men) had PRK to correct myopia. Corneal epithelial healing time was measured and corneal epithelial permeability to sodium fluorescein evaluated by fluorophotometry 1, 2, and 3 weeks after surgery. Epithelial permeability showed a statistically significant increase 1 week after surgery and returned to its preoperative level 1 week later. Comparative studies according to epithelial healing day and corrected diopter showed results that were not statistically significant (P > .05). These results suggest that PRK delays complete reconstruction of corneal epithelial barrier function. In humans, the corneal epithelium regained its normal barrier function 2 weeks after PRK. Thus, at least during these weeks, care should be taken to minimize further epithelial trauma.


Nucleotide sequence of the gene for the hole-forming toxin aerolysin of Aeromonas hydrophila.
The gene for the hole-forming toxin aerolysin from Aeromonas hydrophila was sequenced. Although most of the sequence seems unrelated to that of Staphylococcus aureus alpha-toxin, both proteins are very hydrophilic, and they each contain a nearly identical string of 10 amino acids.


The Impact of COVID-19 on Clubhouse Employment Programs.
The Clubhouse model of psychosocial rehabilitation provides several employment opportunities to individuals who experience mental health concerns, including transitional, supported, and independent employment. The COVID-19 pandemic resulted in Clubhouses having to adapt existing programs to online formats. Employment programs were further impacted, as many workplaces in the community closed or reduced capacity. The present study aimed to examine the rates of involvement in transitional, supported, and independent employment across six Clubhouses in Canada throughout the pandemic. 462 members completed surveys at five time points pertaining to participation in Clubhouse employment programs. The data was analyzed using Cochran's Q tests to determine differences in employment rates across time points. The results demonstrated an overall decrease in transitional and supported employment rates throughout the pandemic. Conversely, rates of independent employment were unchanged. It is evident that Clubhouse employment programs assist members in obtaining employment. The results suggest Clubhouses may benefit from exploring novel employment opportunities to support their members, such as remote work.


Target-based discovery of novel herbicides.
In the past 10 years, strategies for the first steps of herbicide discovery have switched from the testing of chemicals for efficacy on whole plants towards the use of in-vitro assays against molecular targets. Many different approaches have been developed to identify bona fide targets for in-vitro screening. Developments in functional genomics and in pharmaceutical research could aid the development of assay systems for the evaluation of chemicals for their suitability as lead structures in herbicide discovery.


Left ventricular rupture after mitral valve replacement: endocardial repair with pericardial patch.
A patient with type I left ventricular rupture after mitral valve replacement was successfully treated by suturing a pericardial patch to the healthy endocardium around the tear.


Evaluating the energy efficiency-enhancing potential of the digital economy: Evidence from China.
Improving energy efficiency can go a long way in helping China address environmental problems it currently faces and help deliver on its pledge of achieving carbon neutrality by 2060. At the same time, innovative production technologies based on digital solutions continue to attract significant attention, owing to their potential to provide environmentally sustainable development opportunities. This study explores whether the digital economy can improve energy efficiency by facilitating input reallocation and promoting better information flows. We rely on a panel of 285 Chinese cities for the period 2010-2019 and a so-called slacks-based efficiency measure incorporating socially undesirable outputs to obtain energy efficiency from the decomposition of a productivity index. Our estimation results demonstrate that the digital economy can promote better energy use efficiency. More specifically, a 1-percentage point increase in the size of the digital economy leads to an average increase of around 14.65 percentage points in energy efficiency. This conclusion still holds under a two-stage least-squares procedure used to mitigate endogeneity. The efficiency-enhancing impact of digitalization is heterogeneous and depends on factors such as resource endowment, city size, and geographical location. Additionally, our results suggest that digital transformation within a particular region has an adverse effect on energy efficiency in that region's neighboring areas due to negative spatial spillover effects. These negative spillovers outweigh the positive direct effect on energy efficiency that can be attributed to a growing digital economy.


Chymotrypsin- and trypsin-type serine proteases in rat mast cells: properties and functions.
Two of the major enzymes present in and released from rat mast cells are chymotrypsin-type serine protease (chymase) and trypsin-type serine protease (tryptase), and these have been postulated to be important in the inflammatory reactions. There have been no clear data regarding the trypsin-type protease in rat mast cells. Tryptase was recently purified from rat peritoneal mast cells with an associated protein (trypstatin) that inhibited the protease activity above pH 7.5. Chymase was also purified from rat peritoneal cells by employing a one-step method involving hydrophobic chromatography on octyl-Sepharose 4B or arginine-Sepharose 4B. The properties of chymase and tryptase were described in relation to substrate specificity and their relative sensitivity to inhibitors. It was found that proteolytic activities of these enzymes were modulated by naturally occurring substances, such as phosphoglycerides, long-chain fatty acids, and trypstatin. There is as yet little evidence for the physiological roles of these enzymes in the inflammatory reaction. It has been found that the specific, low-molecular-weight inhibitor of chymase, chymostatin, and that of tryptase, leupeptin, inhibit histamine release induced by addition of anti-rat IgE to mast cells. However, the inhibitors with molecular weights of more than 6000 were found to have no effect in this process. The data suggest that chymase and tryptase in mast cell granules play a crucial or significant role in the process of degranulation.


Induction of Colonic M Cells during Intestinal Inflammation.
Intestinal M (microfold) cells are specialized epithelial cells overlying lymphoid tissues in the small intestine. Unlike common enterocytes, M cells lack an organized apical brush border, and are able to transcytose microparticles across the mucosal barrier to underlying antigen-presenting cells. We found that in both the dextran sodium sulfate and Citrobacter rodentium models of colitis, significantly increased numbers of Peyer's patch (PP) phenotype M cells were induced at the peak of inflammation in colonic epithelium, often accompanied by loosely organized lamina propria infiltrates. PP type M cells are thought to be dependent on cytokines, including tumor necrosis factor (TNF)-α and receptor activator of nuclear factor kappa-B ligand; these cytokines were also found to be induced in the inflamed tissues. The induction of M cells was abrogated by anti-TNF-α blockade, suggesting that anti-TNF-α therapies may have similar effects in clinical settings, although the functional consequences are not clear. Our results suggest that inflammatory cytokine-induced PP type M cells may be a useful correlate of chronic intestinal inflammation.


Lactobacillus delbrueckii subsp. bulgaricus strain TCI904 reduces body weight gain, modulates immune response, improves metabolism and anxiety in high fat diet-induced obese mice.
The multiple probiotic characteristics of strain TCI904 isolated in this study from natural fermented milk were investigated using a mouse model. TCI904 was identified as Lactobacillus delbrueckii subsp. bulgaricu (LDB), a well-known lactic acid starter bacterium found in yogurt. TCI904 exhibited an outstanding pancreatic lipase inhibition activity among several strains of lactic acid bacteria in vitro. Its in vivo effects were further studied. In a comparison of mice fed a high-fat diet (HFD) and those fed a HFD combined with TCI904 for 9 weeks, differences were observed in various aspects of health, and the adverse effects of a HFD were prevented in the latter group. TCI904 effectively prevented fat and body weight accumulation without reducing food intake; it also modulated innate immunity and increased the level of IgA in feces, reversing the increased blood sugar and insulin levels and attenuated the hyperlipidemia caused by a HFD. Based on biochemical test data, compared with the HFD group, a HFD combined with TCI904 induced significant lowering of insulin resistance indicator, homeostasis model assessment-insulin resistance (HOMA-IR) and atherogenic indices of plasma (AIP), the atherogenic coefficient (AC) and cardiac risk ratio (CRR) and increased the cardioprotective index (CPI). In addition, the administration of TCI904 alleviated mood disorders caused by a HFD. Taking the recommended human dose of TCI904 did not affect the liver or kidney function, indicating that TCI904 has sufficient in vivo safety. Taken together, the results of the present study contributed towards validation of the probiotic benefits of lactic acid starter microflora. Orally taken TCI904 exhibited positive immune- and metabolic-modulating, and anxiolytic properties, especially in HFD-induced obesity. The online version contains supplementary material available at 10.1007/s13205-022-03356-3.


Aquaporins in health and disease.
Aquaporins (AQPs) are transmembrane channel proteins that mainly facilitate the water translocation through the plasma cell membrane. For several years these proteins have been extensively examined for their biologic role in health and their potential implication in different diseases. Technological improvements associated with the methods employed to evaluate the functions of the AQPs have provided us with significant new knowledge. In this chapter, we will examine the role of AQPs in health and disease based on the latest currently available evidence.


Investigation on the lubrication component and mechanism for a biolubricant isolated from the agro-waste resource of Codonopsis pilosula.
Waste plant resource provides a new sustainable feedstock for the biolubricant, and purification of the effective components in biomass oil is vital to improve the performance of biolubricant. In this work, the crude extract of the aerial part of Codonopsis pilosula was divided into four different parts by petroleum ether, ethyl acetate, n-butanol and water, respectively. Their thermal stability, lubricating performances and mechanisms have been systematically investigated. In the four extracts, the petroleum ether extract displays the best thermal stability and lubricating performance over the entire test conditions, and other three extracts are confronted with lubrication failure at high loads and elevated temperatures. Triterpenoid saponin, typical for n-butanol extract exhibit the best lubricity at room temperature, followed by the fatty acid derivatives as phosphatidylcholine; flavonoid, and sugar exhibit poor lubricity. At high temperature, only the petroleum ether extract retains the good lubricity.


Dietary Quality and Dietary Inflammatory Potential During Pregnancy and Offspring Emotional and Behavioral Symptoms in Childhood: An Individual Participant Data Meta-analysis of Four European Cohorts.
The impact of maternal diet during pregnancy on child neurodevelopment is of public health and clinical relevance. We evaluated the associations of dietary quality based on the Dietary Approaches to Stop Hypertension (DASH) score and dietary inflammatory potential based on the energy-adjusted Dietary Inflammatory Index (E-DII) score during pregnancy with emotional and behavioral symptoms of offspring at 7 to 10 years of age. Individual participant data for 11,870 mother-child pairs from four European cohorts participating in the ALPHABET project were analyzed. Maternal antenatal DASH and E-DII scores were generated from self-completed food frequency questionnaires. Symptoms of depression and anxiety, aggressive behavior, and attention-deficit/hyperactivity disorder in children were assessed using mother-reported tests and classified within the normal or borderline/clinical ranges using validated cutoffs. Adjusted odds ratios were determined by multivariable logistic regression models and aggregated by the two-level individual participant data meta-analysis method. Higher maternal DASH scores (indicating better dietary quality) were associated with lower risk of depressive and anxiety symptoms, aggressive behavior symptoms, and attention-deficit/hyperactivity disorder symptoms within the borderline/clinical ranges: odds ratio [OR] 0.97, 95% confidence interval [CI], 0.95-0.99; OR 0.97, 95% CI, 0.94-0.99; OR 0.97, 95% CI, 0.95-0.98, per one-unit DASH score increase, respectively. For depression and anxiety, aggressive behavior, and attention-deficit/hyperactivity disorder symptoms, a one-unit increase in E-DII scores (a more proinflammatory diet) was associated with a 7% increased risk of all three analyzed emotional and behavioral symptoms: OR 1.07, 95% CI, 1.03-1.11; OR 1.07, 95% CI, 1.02-1.13; OR 1.07, 95% CI, 1.01-1.13, respectively. Our findings suggest that a maternal low-quality and proinflammatory diet may increase the risk of emotional and behavioral symptoms in children.


Embolized air collection in the superior vena cava of "upright" sheep.
In 34 studies on six "upright" anesthetized sheep central venous pressure from sites in the upper and lower superior vena cava (SVC) was recorded before, during, and after the injection into a neck vein of 1-ml increments of air every minute for 15 min. After the injection of air, the pressure recorded from the upper site increased significantly. This increase was the result of air collecting in the SVC with a consequent loss or partial loss of the SVC hydrostatic pressure difference. The time of onset and the duration of collection were not influenced by hyper- or hypovolemia nor by 1 kPa positive end-expiratory pressure. The readily identifiable change in the venous pressure in the upper SVC provided an earlier and more reliable warning of these small-volume air emboli than did a Doppler probe directed at the right side of the heart.


Evaluation of the effects of enzootic pneumonia in pigs on weight gain and days to slaughter under New Zealand conditions.
The effects of enzootic pneumonia on average daily weight gain and number of days taken to reach slaughter weight was studied in 333 bacon-weight pigs. Each 1% of lung volume affected by enzootic pneumonia was shown to reduce average daily gain by 2.2 grams and increase the numbers of days to slaughter by 0.61 days. The cost of these reductions in performance was calculated to be about NZD 1 for each 1% of lung affected.


Dot-blot immunodetection as a versatile and high-throughput assay to evaluate recombinant GPCRs produced in the yeast Pichia pastoris.
One of the major objectives of the Membrane Protein Network program (MePNet, www.mepnet.org) is to express one hundred G-protein-coupled receptors (GPCRs) in the yeast Pichia pastoris. We have developed an antibody-based assay in order to select for the best behaving clones at each step of the receptor preparation, from expression to solubilization. This assay allowed us to quantify the expression of Flag-tagged GPCRs present in various sample types, from crude P. pastoris extracts to native membrane preparations and detergent solubilised fractions. It combines the specificity of ELISA, the sensitivity of enhanced chemiluminescence detection and the speed of high-throughput screening, and can detect as low as 0.001% (w/w) flag-tagged recombinant receptor present in a crude extract. The method was applied to sort recombinant GPCR clones, to rank receptor expression levels and to screen for detergent solubilization efficiency using the human beta2-adrenergic receptor expressed in P. pastoris as a benchmarking standard.


Antioxidant, antibacterial and cytotoxic effects of the phytochemicals of whole Leucas aspera extract.
To investigate the antioxidant, antibacterial and cytotoxic activity of whole Leucas aspera (Labiatae) (L. aspera) alcoholic extract. Whole L. aspera powder was extracted by absolute ethanol (99.50%). The ethanolic extract was subjected to antioxidant, antibacterial and brine shrimp lethality assay. The extract showed potent radical scavenging effect (antioxidant) with IC50 value of (99.58±1.22) µg/mL which was significant (P<0.01) in comparison to ascorbic acid with IC50 value of (1.25±0.95) µg/mL. In case of antibacterial screening, the extract showed notable antibacterial effect against the tested microbial strains. Significant (P<0.05) zone of inhibitions against Gram positive Bacillus subtilis [(12.00±1.32) mm] and Bacillus megaterium [(13.00±1.50) mm], Staphylococcus aureus [(8.00±0.50) mm] and Gram negative Salmonella typhi [(6.00±0.50) mm], Salmonella paratyphi [(8.00±1.00) mm], Shigella dysenteriae [(9.00±1.32) mm] and Vibrio cholerae [(9.00±0.66) mm] was observed. In brine shrimp lethality bioassay, the extract showed the LC50 value as (181.68±2.15) µg/mL which was statistically significant (P<0.01) compared to positive control vincristine sulfate [LC50=(0.76±0.04) µg/mL]. The results demonstrate that the ethanolic extract of L. aspera could be used as antibacterial, pesticidal and various pharmacologic actives.


LBX2-AS1/miR-219a-2-3p/FUS/LBX2 positive feedback loop contributes to the proliferation of gastric cancer.
Long non-coding RNAs (lncRNAs) are increasingly investigated in numerous carcinomas containing gastric cancer (GC). The aim of our research is to inquire about the expression profile and role of LBX2-AS1 in GC. The expressions of LBX2-AS1, miR-219a-2-3p, FUS and LBX2 were measured by qRT-PCR. Western blot evaluated FUS and LBX2 protein levels. Cell proliferation and apoptosis were, respectively, evaluated by CCK-8, colony formation, EdU, flow cytometry and TUNEL assays. FISH and subcellular fractionation assays examined the position of LBX2-AS1. The binding between genes were certified by RIP, RNA pull-down, ChIP and luciferase reporter assays. Pearson correlation analysis analyzed the association of genes. Kaplan-Meier method detected the relationship of LBX2-AS1 expression with overall survival. The up-regulation of LBX2-AS1 in GC tissues and cells was verified. Function assays proved that LBX2-AS1 down-regulation restricted the proliferation ability. Then, we unveiled the LBX2-AS1/miR-219a-2-3p/FUS axis. Additionally, LBX2-AS1 positively regulated LBX2 mRNA stability via FUS. LBX2 transcriptionally modulated LBX2-AS1. In the end, rescue and in vivo experiments validated the whole regulatory mechanism. LBX2-AS1/miR-219a-2-3p/FUS/LBX2 positive feedback loop mainly affected the proliferation and apoptosis abilities of GC cells, offering novel therapeutic targets for the treatment of patients with GC.


Genetic association of an apolipoprotein C-I (APOC1) gene polymorphism with late-onset Alzheimer's disease.
Since a deletion/insertion polymorphism in the promoter region of the apolipoprotein C-I (APOC1) gene has been reported to be associated with late-onset Alzheimer's disease (LOAD), we examined the hypothesis in a Korean population with 120 LOAD cases and 132 age-matched controls. The frequency of APOC1 insertion allele (H2) was significantly increased in LOAD than in controls, giving an odds ratio of 3.3 (95% CI 2.0-5.5, P<0.0001). Logistic regression analysis revealed that the interaction model between APOE epsilon4 and APOC1 H2 yielded larger odds ratio than other models including either APOE epsilon4 or APOC1 H2 alone. In addition, the association between APOC1 H2 and LOAD remained significant after adjustment of the effect of APOE epsilon4 (P=0.036). These results support previous observations that the APOC1 might be an additional susceptibility gene for LOAD.