circCRKL suppresses the progression of prostate cancer cells by regulating the miR-141/KLF5 axis.
Prostate cancer (PCa) is a prevalent human malignancy in males. Circular RNA circCRKL (Hsa_circ_0001206) was reported to be lowly expressed in PCa tissues. However, the regulatory role of circCRKL in PCa is poorly defined. Levels of circCRKL, microRNA-141 (miR-141), and Kruppel-like factor (KLF5) were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Cell cycle progression, apoptosis, migration, and invasion were examined by Flow cytometry, Wound healing, and transwell assays. The underlying relationship between miR-141 and circCRKL or KLF5 was predicted by starBase, and then verified by a dual-luciferase reporter, RNA Immunoprecipitation (RIP), and RNA pull-down assays. The protein level of KLF5 was assessed by western blot assay. The biological role of circCRKL was detected by a xenograft tumor model in vivo. CircCRKL and KLF5 were decreased, and miR-141 was increased in PCa tissues and cells. The functional analysis discovered that the overexpression of circCRKL repressed cell cycle progression, migration, invasion, and boosted apoptosis of PCa cells. Mechanically, circCRKL could positively regulate KLF5 expression by sponging miR-141. In addition, circCRKL upregulation could hinder PCa tumor growth in vivo. These findings revealed that circCRKL inhibited the progression of PCa through upregulating KLF5 expression by sponging miR-141, elucidating a novel regulatory pathway in PCa cells. Our research suggested an underlying circRNA-targeted therapy for PCa.


Role of radiofrequency ablation in the management of supraventricular arrhythmias: experience in 760 consecutive patients.
Several reports have demonstrated that radiofrequency catheter ablation provides effective control of a variety of supraventricular tachycardias. However, the efficacy, complications, risk of arrhythmia recurrence, and follow-up survival analysis have not been reported in a large series of consecutive patients with supraventricular arrhythmias with diverse electrophysiologic mechanisms. This report details the results of radiofrequency catheter ablation in 760 consecutive patients (386 males, 374 females) with a wide variety of supraventricular tachycardias treated at one center. Arrhythmias were associated with the presence of an accessory pathway in 363 patients (384 accessory pathways), including four patients with Mahaim fibers and eight patients with the permanent form of junctional reciprocating tachycardia. The mechanism of the clinical arrhythmia was AV nodal reentrant tachycardia in 245 patients, and a primary atrial tachycardia in 20 patients (ectopic atrial tachycardia in 16 patients and sinus nodal reentry in 4 patients). Ablation of the reentrant circuit of atrial flutter within the right atrium was attempted in 13 patients. AV node ablation and permanent pacemaker implantation were performed in 119 patients with medically refractory atrial fibrillation or flutter. Radiofrequency catheter ablation was successful in 346 of 363 patients (95.3%, CI 93.1%-97.5%) with accessory pathways (367 of 384 pathways, 95.6%, CI 93.5%-97.6%) with a complication rate of 1.1% and a recurrence rate of 5.5%. Successful accessory pathway ablation was achieved for 179 of the first 192 pathways treated (93.2%, CI 89.7%-96.6%) and increased to 188 of 192 pathways (97.9%, CI 95.9%-99.9%) over the second half of the series. AV nodal reentry was successfully abolished in 244 of 245 patients (99.6%, CI 98.8%-100%) by selective ablation of the slow pathway in 234 patients and the fast pathway in 10 patients. The complication rate in this group was 2.0% with a recurrence rate of 6.5%. All 20 primary atrial tachycardias were successfully ablated with no complications and a recurrence rate of 15%. The reentrant circuit of atrial flutter was ablated successfully in 10 of 13 patients (77%) with recurrent atrial flutter in one additional patient. Complete AV block was achieved in 117 of 119 (98.3%, CI 96.0%-100%) patients with atrial fibrillation or flutter treated by AV nodal ablation with a complication rate of 0.8% and recurrence of AV conduction in 6%. The median duration of fluoroscopy exposure for the population was 23.4 minutes. The overall primary success rate for the entire population was 97.0% (737 of 760 patients, CI 95.8%-98.2%). Thus, the results of this large series of patients demonstrates the safety and efficacy of radiofrequency ablation for the treatment of a wide variety of supraventricular arrhythmias. It also appears that increasing experience with these procedures increases the rate of successful ablation and decreases the risk of complications.


Using technology to bridge the transition from pediatric to adult health care.
There are unique challenges presented during the transition from pediatric to adult health care for adolescents with chronic medical conditions, and many do not transition smoothly. Although there is little research on how mobile applications can influence the transition process specifically, research shows technology, in general, can be advantageous to the transition process for adolescents. Ample literature exists on how adolescents are avid users of technology. The Children's Medical Services program in a large urban county in the southern United States lacked an efficient system for transitioning the care of children with special needs to the adult health care setting. Qualitative semistructured interviews and pre-post tests were conducted with 23 adolescent participants with chronic medical conditions. Multiple choice questions elicited information from four categories: knowledge of medical condition, organization/health care system navigation, identified adult health care provider, and awareness of available resources. A novel website and smartphone application designed to aid adolescents and young adults during transition were developed. Gain scores from pre-post tests showed an increase in all 4 sections of the survey: knowledge of medical condition-21% increase, organization/health care system navigation-15.3% increase, identified health care provider-32% increase, and awareness of available resources-19.3% increase. All 23 adolescent participants reported that the application would be useful for managing their health information. Smartphone applications can be helpful for adolescents in their transition into adult health care. Such applications also have potential to increase confidence and independence in managing health care needs.


New experimental finding of dangerous autonomic ganglia changes in cardiac injury following subarachnoid hemorrhage; a reciprocal culprit-victim relationship between the brain and heart.
The vagal, stellate, and cardiac ganglia cells changes following subarachnoid hemorrhage (SAH) may occur. This study aimed to investigate if there is any relation between vagal network/stellate ganglion and intrinsic cardiac ganglia insult following SAH. Twenty-six rabbits were used in this study. Animals were randomly divided as control (GI, n = 5); SHAM 0.75 cc of saline-injected (n = 5) and study with autologous 1.5 cc blood injection into their cisterna magna(GIII, n = 15). All animals were followed for three weeks and then decapitated. Their motor vagal nucleus, nodose, stellate, and intracardiac ganglion cells were estimated by stereological methods and compared statistically. Numerical documents of heart-respiratory rates, vagal nerve- ICG, and stellate neuron densities as follows: 276 ± 32/min-22 ± 3/min-10.643 ± 1.129/mm3-4 ± 1/mm3-12 ± 3/mm3 and 2 ± 1/cm3 in the control group; 221 ± 22/min-16 ± 4/min-8.699 ± 976/mm3-24 ± 9/mm3-103 ± 32/mm3 and 11 ± 3/cm3 in the SHAM group; and 191 ± 23/min-17 ± 4/min-9.719 ± 932/mm3-124 ± 31/mm3-1.542 ± 162/mm3 and 32 ± 9/cm3 in the SAH (study) group. The animals with burned neuro-cardiac web had more neurons of stellate ganglia and a less normal neuron density of nodose ganglia (p < 0.005). Sypathico-parasympathetic imbalance induced vagal nerve-ICG disruption following SAH could be named as Burned Neurocardiac Web syndrome in contrast to broken heart because ICG/parasympathetic network degeneration could not be detected in classic broken heart syndrome. It was noted that cardiac ganglion degeneration is more prominent in animals' severe degenerated neuron density of nodose ganglia. We concluded that the cardiac ganglia network knitted with vagal-sympathetic-somatosensitive fibers has an important in heart function following SAH. The neurodegeneration of the cardiac may occur in SAH, and cause sudden death.


Neuron-glial cell communication in the traumatic stress-induced immunomodulation.
We have previously reported that neuron and glia could collaboratively govern the immunomodulation in traumatic rats. Herein, we characterized the sequential involvement of cortical neuron, microglia, and astrocytes in the traumatic stress-mediated neuroimmune modulation. At day 1 of trauma, transient extracellular signal related kinase 1/2 (ERK1/2) activation was initiated in neuron and microglia, which was accompanied by RSK-1 expression in the cytosol. At day 3 of trauma, persistent ERK1/2 activation occurred in astrocytes, which were destined for the nucleus leading to Elk-1 expression. Furthermore, the functional overlap of ERK1/2 and neuroligin 1 in astrocytes was strengthened at day 3 of trauma and responsible for the recovery from the immnosuppression. These effects could be disrupted by β-neurexin blockade. Altogether, we proposed the mechanism underlying the traumatic stress-induced immunosuppression, in which local activity ensured the initial establishment of neural circuitry in the frontal cortex. ERK1/2-signaling events are required for the temporal and spatial coordination between neuron and glial cells.


Prognostic importance of survivin, Ki-67, and topoisomerase IIα in ovarian carcinoma.
Stage, tumor grade and histological subtype determine the clinical behavior in ovarian tumors. Some additional factors are related to tumor cell biology and are the useful predictors for identifying the patients with poor prognosis. The aim of this study is to evaluate the prognostic significance of survivin, Ki-67 and Topoisomerase IIα (TOPO IIα) in epithelial ovarian cancer (EOC). Seventy-three patients with EOC were included in this study. Survivin, Ki-67 and TOPO IIα expressions were studied by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections. Nuclear staining for all antibodies was scored on a three-tiered system and more than 10 % staining was accepted as expression. The relationship between the expressions of survivin, Ki-67, TOPO IIα and clinicopathological parameters including age, stage, grade, platinum resistance and survival was evaluated. Survivin, Ki-67 and TOPO IIα expressions were found in 20, 82 and 86 % of the tumors, respectively. Ki-67 and TOPO IIα expressions were found to be related to poor overall survival (p = 0.005, 0.004, respectively), while survivin expression was not associated with overall survival. There was no association between TOPO IIα and Ki-67 expressions and histological subtype, stage or grade. However, we found an important relationship between TOPO IIα expression and platinum resistance (p = 0.044). Platinum resistance was found to be an independent prognostic factor in EOC. Ki-67 and TOPO IIα expressions were found to be related to poor overall survival, and TOPO IIα expression was found to be associated with platinum resistance.


Pasteurella multocida antigen-induced in vitro lymphocyte immunostimulation, using whole blood from cattle and turkeys.
A whole blood lymphocyte stimulation assay to study cell-mediated immune responses in bovine pasteurellosis was developed. Peripheral blood lymphocytes from cattle artificially immunised with three Asiatic haemorrhagic septicaemia strains of Pasteurella multocida exhibited higher stimulation indices when incubated with antigen preparations from homologous strains than with the heterologous shipping fever strain. Lymphocytes from cattle immunised with the shipping fever strain of P multocida exhibited a higher stimulation index when incubated with an antigen preparation from the homolgous strain than with antigen preparations from heterologous haemorrhagic septicaemia strains. These results suggest that immunogenic differences exist between the haemorrhagic septicaemia strains and the shipping fever strain of P multocida. An assay using turkey whole blood lymphocytes was also developed. The use of small amounts of whole blood, microtitre plates, either 125I iododeoxyuridine or 3H-thymidine as the labelling agent, and a multiple cell-culture harvester makes the method simple, rapid and suitable for the study of immune competence and cell-mediated immune responses in turkeys on a flock basis.


Effectiveness of aortic valve replacement in Heyde syndrome: a meta-analysis.
Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated to resolve all three associated disorders. A systematic review and meta-analysis were performed to obtain best estimates of the effect of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding. A literature search was performed to identify articles on Heyde syndrome and aortic valve replacement up to 25 October 2022. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 h (T1), 24-72 h (T2), 3-21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios were calculated using random-effects models. Thirty-three studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1054), and 11 observational studies on gastrointestinal bleeding (n = 300) were identified. One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79%-91%) at T1, 90% (74%-96%) at T2, 92% (84%-96%) at T3, and 87% (67%-96%) at T4. The pooled proportion of Heyde patients with gastrointestinal bleeding cessation was 73% (62%-81%). Residual aortic valve disease was associated with lower recovery rates of acquired von Willebrand syndrome (RR 0.20; 0.05-0.72; P = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40-0.81; P = 0.002). Aortic valve replacement is associated with rapid recovery of the bleeding diathesis in Heyde syndrome and gastrointestinal bleeding cessation. Residual valve disease compromises clinical benefits.


Bioanalysis in clinical development of tasquinimod using liquid chromatography/tandem mass spectrometry.
Tasquinimod (ABR-215050) is an oral drug in clinical development for treatment of patients with castrate resistant prostate cancer. This paper describes a method for the determination of tasquinimod in human plasma. The method is based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) using stable isotope labeled tasquinimod as internal standard (IS). The plasma samples were processed by protein precipitation using acidic acetonitrile containing the IS. The precipitated samples were centrifuged and the supernatant was injected directly into the LC-MS/MS system. Chromatographic separation was performed on a reversed phase column using fast gradient elution, with a total run cycle time of 4 min. The method was validated with respect to accuracy, precision, dynamic range, lower limit of quantification, selectivity and robustness. Furthermore, the stability of tasquinimod in spiked plasma, in processed extracts and in incurred samples was thoroughly studied. The method was validated in the range of 1.0-2400 nmol/L, defining the lower and upper limits of quantification. The repeatability, reproducibility and overall bias were 1.5-7.1%, 3.5-7.4%, and 1.3-4.7%, respectively, in the range of 1-2000 nmol/L. Excellent selectivity was demonstrated in the validation, as well as in study samples from both healthy volunteers and cancer patients. Robustness was demonstrated by the calculated carry-over as low as 0.06%, and by an incurred sample reproducibility (ISR) experiment where 97% of the reanalyzed samples fulfilled the acceptance criteria of 20% deviation from initial analysis result. Also, tasquinimod was found to be stable in all investigated matrices, including in incurred samples. In an incurred sample stability (ISS) investigation, tasquinimod was demonstrated to be stable for 24 months, and 97% of the reanalyzed samples were within 20% from the initial analysis result. In conclusion, the method was demonstrated to be accurate, precise, robust and reliable for the determination of tasquinimod. The method was successfully used in several clinical studies for the support of pharmacokinetic and pharmacodynamic evaluations.


Effect of patient age on accuracy of primary MRI signs of long head of biceps tearing and instability in the shoulder: an MRI-arthroscopy correlation study.
To determine the effect of patient age on the accuracy of primary MRI signs of long head of biceps (LHB) tendon tearing and instability in the shoulder using arthroscopy as a reference standard. Subjects with MRI studies and subsequent arthroscopy documenting LHB tendon pathology were identified and organized into three age groups (18-40, 41-60, 61-87). Normal and tendinopathic tendons were labeled grade 0, partial tears grade 1 and full tears grade 2. Two radiologists blinded to arthroscopic data graded MRI studies independently. Prevalence of disease, MRI accuracy for outcomes of interest, and inter-reader agreement were calculated. Eighty-nine subjects fulfilled inclusion criteria with 36 grade 0, 36 grade 1 and 17 grade 2 tendons found at arthroscopy. MRI sensitivity, regardless of age, ranged between 67-86% for grade 0, 72-94% for grade 1 and 82-94% for grade 2 tendons. Specificity ranged between 83-96% for grade 0, 75-85% for grade 1 and 99-100% for grade 2 tendons. MRI accuracy for detection of each LHB category was calculated for each age group. MRI was found to be least sensitive for grade 0 and 1 LHB tendons in the middle-aged group with sensitivity between 55-85% for grade 0 and 53-88% for grade 1 tendons. Agreement between MRI readers was moderate with an unweighted kappa statistic of 62%. MRI accuracy was moderate to excellent and agreement between MRI readers was moderate. MRI appears to be less accurate in characterizing lower grades of LHB tendon disease in middle-aged subjects.


Mental chronometry and individual differences: modeling reliabilities and correlations of reaction time means and effect sizes.
We used a general stage-based model of reaction time (RT) to investigate the psychometric properties of mean RTs and experimental effect sizes (i.e., differences in mean RTs). Using the model, formulas were derived for the reliabilities of mean RTs and RT difference scores, and these formulas provide guidance about the number of trials per participant needed to obtain reliable estimates of these measures. In addition, formulas were derived for various different types of correlations computed in RT research (e.g., correlations between a mean RT and an external non-RT measure, between two mean RTs, between a mean RT and an RT effect size). The analysis revealed that observed RT-based correlations depend on many parameters of the underlying processes contributing to RT. We conclude that these correlations often fail to support the inferences drawn from them and that their proper interpretation is far more complex than is generally acknowledged.


Enzyme technology and bioprocess engineering.
The impact of directed evolution and site-specific mutagenesis on the industrial utility of enzymatic catalysis through the modification of enzyme structure and function is clearly an important area of research in bioprocess engineering. High-throughput screening for novel or improved enzyme activities, both by more efficiently exploring nature's diversity and by creating new diversity in the test tube, allows new bioprocesses to be developed. Similarly, innovations in enzyme technology that address novel ways to apply enzymes in bioprocesses also have an impact on bioprocess engineering. Several recent developments have been made in this latter aspect of bioprocess engineering.


Comparison between a laser fluorescence device and visual examination in the detection of occlusal caries in children.
Occlusal surfaces of molars are especially susceptible to the development of caries due to the features, such as pits and deep fissures, of their anatomical structure. To evaluate the efficiency of DIAGNOdent laser fluorescence measurements in comparison with visual examination for occlusal caries detection for first permanent molars in children. The study involved 156 permanent molar teeth in 40 children aged 7-12 years. A relatively new technology, the fluorescence laser DIAGNOdent pen, was used for detecting and diagnosing caries on the occlusal surfaces of molars. The visual examination of fissures was based on the Ekstrand classification system. The results showed a strong relationship between examination with the DIAGNOdent and visual inspection. DIAGNOdent's sensitivity and specificity were 97% and 52%, respectively, indicating that the laser fluorescence DIAGNOdent pen is a reproducible and accurate diagnostic tool that may be very helpful in conjunction with visual examination in the detection of occlusal caries in permanent molars in children.


The Relationship Between Greenspace Exposure and Psychopathology Symptoms: A Systematic Review.
Greenspace exposure is associated with psychological benefits. In this systematic review, we summarized and critically evaluated the literature on the relationship between greenspace exposure (i.e., objective and subjective assessments of interactions with nature) and psychopathology incidence and symptom severity in those with and without a clinical diagnosis. A secondary aim of our review was to examine potential interactions between greenspace exposure and urban environmental features (e.g., pollution, population density) associated with poorer mental health. We identified 40 studies published between January 1, 1981, and July 31, 2020, from PubMed and PsycINFO electronic database search. Although heterogeneous in assessments of greenspace exposure and psychopathology symptom domain, the majority of cross-sectional and longitudinal evidence found that objectively assessed greenspace exposure (e.g., satellite measures of greenery) was related to less severe symptoms and lower incidence of psychopathology in children (e.g., attention-deficit/hyperactivity disorder symptoms) and adults (e.g., depression symptoms). In addition, five studies that assessed urban environmental features suggest that greenspace exposure may show a net positive relationship with psychopathology over and above the absence of urban features. We discuss limitations of the literature and future directions, including more mechanistic work to delineate the potential cognitive, affective, and behavioral factors that may contribute to the beneficial relationship between greenspace exposure and psychological health.


An estimation of the incidence and demographic picture of the major hemoglobinopathies in Belgium (from a confidential inquiry).
An estimation of the incidence and demographic picture of the major hemoglobinopathies in Belgium has been approached through a confidential inquiry sent to 228 pediatric and adult hematological departments. Forty-two percent of responses showed that 417 patients are known in Belgium: 83% with sickle cell disease, 13% with beta-thalassemia (beta-thal) major, 2% with beta-thal intermedia, and 1% with Hb H disease. Twenty-five percent of the sickle cell disease patients and 54% of those suffering from a beta-thal major were older than 20 years. Three hospitals ensure the follow-up of 70% of the patients and are situated in Brussels, Belgium; a follow-up of less than 20 patients was reported at 21 centers. These results confirm that sickle cell disease is the major hemoglobinopathy in Belgium; it concerns mostly pediatricians but adult hematologists are also confronted with these pathologies. Therefore, it is necessary to implement integrated programs of prevention and treatment.


Potential for transfusion-associated graft-versus-host disease due to apheresis platelets matched for HLA class I antigens.
Transfusion-associated graft-versus-host disease (TA-GVHD) has been reported in immunocompetent recipients of nonirradiated cellular blood components from donors who are homozygous for an HLA haplotype shared with the patient. In these cases, donor lymphocytes have no antigens foreign to the recipient, and this similarity in HLA antigens appears important for the development of TA-GVHD. Experience with 65 patients receiving apheresis platelets matched for class I HLA antigens was reviewed to determine the incidence of such a transfusion among HLA-matched, unrelated donor-recipient pairs. In 5 percent of transfusions (31/673), the patient received lymphocytes from a donor exhibiting no antigens foreign to the recipient, but the patient had additional HLA-A or -B antigens not present on donor lymphocytes. Twenty-three percent (n = 15) of patients received at least one such transfusion. In addition, most patients were immunosuppressed as a result of their underlying disease or therapy, which may decrease the degree of antigen matching required to initiate TA-GVHD. Until the pathogenesis of this disease is better understood, it is recommended that the transfusion of an HLA-matched cellular blood component be considered a risk factor for the development of TA-GVHD regardless of the patient's immune status, and that all such blood components be irradiated.


New frontiers in proton therapy: applications in breast cancer.
The aim of this article is to review published data on proton therapy in the multimodality treatment of breast cancer so as to provide an overview of the advantages and critical issues relating to this irradiation modality. In-silico studies show a clear advantage in terms of dose homogeneity to the target and dose reduction to the non-target structures including heart, lungs, and healthy breast tissues. Clinical studies have shown the feasibility of proton therapy in breast cancer and allowed optimizing the technique by using multiple beams and intensity modulation. Proton therapy is able to optimize the dose to the target and to reduce the irradiation of the healthy tissues. Clinical studies are expected to show a decreased risk of late side effects with potential improvement of the quality of life of breast cancer patients.


Transfer the best and biopsy the rest? Blastocyst euploidy rates differ by morphology and day of biopsy.
To determine if blastocyst euploidy rates differ by embryo morphology or day of biopsy. We performed a retrospective analysis of euploidy rates based on patient age, overall embryo morphology grade (good, fair, or poor), and day of biopsy (days 5, 6, or 7) for blastocysts undergoing preimplantation genetic testing for aneuploidy (PGT-A). Our primary analysis included 904 embryos from oocytes age 33-39 years at retrieval. In our primary analysis, euploidy rates were higher for good quality embryos than poor (64% vs. 48%, p < 0.01) and for fair quality embryos than poor (61% vs. 48%, p < 0.01). There was no significant difference in the euploidy rate between good and fair quality embryos (64% vs. 61%, p = 0.56). Embryos biopsied on day 5 were more likely to be euploid than embryos biopsied on day 6 (59% vs. 50%, p < 0.01) or day 7 (59% vs. 37%, p < 0.01). There was no significant difference in the euploidy rate between day 6 and day 7 embryos (50% vs. 37%, p = 0.07). PGT-A may be more useful in cycles where a lower euploidy rate is expected based on age at oocyte retrieval, embryo morphology, and day of biopsy. There may be little benefit to biopsy of embryos with a high euploidy rate. Young patients with one or more good quality day 5 embryos may benefit from a "transfer the best fresh and biopsy the rest" strategy.


Diffusion tensor imaging in schizophrenia.
Diffusion tensor imaging (DTI) is a relatively new neuroimaging technique that can be used to examine the microstructure of white matter in vivo. A systematic review of DTI studies in schizophrenia was undertaken to test the hypothesis that DTI can detect white matter differences between schizophrenia patients and normal control subjects. EMBASE, PubMed, Medline, and PsychInfo were searched online and key journals were searched manually for studies comparing anisotropy (a measure of white matter integrity) between patients and control subjects. Nineteen articles were systematically reviewed. Though 16 studies found differences, methodological and data differences prevented a meta-analysis. Fourteen studies found reduced anisotropy in patients; two studies found only a loss of normal asymmetry. The region of investigation varied across studies, however, and when the same region (for example, the cingulum) was examined in different studies, as many failed to find a difference as found one. These inconsistencies may be the result of small sample sizes and differences in methodology. Diffusion tensor imaging has yet to provide consistent findings of white matter abnormalities in schizophrenia. Its potential as a means of examining anatomical connectivity may be realized with the study of larger, more homogenous groups of subjects and with ongoing improvements in image analysis.


Intralesional immunotherapy of malignant melanoma with mycobacterium smegmatis cell wall skeleton combined with trehalose dimycolate (P3).
The clinical efficacy of intralesional immunotherapy utilizing Mycobacterium smegmatis cell wall skeleton (CWS) and trehalose dimycolate attached to oil droplets was investigated in 15 patients with advanced malignant melanoma. Patients received 300 microgram to 1050 microgram of the CWS combined with one-half that amount of trehalose dimycolate every 1 to 2 weeks for a total of 8 treatments. Therapy was continued if regression of injected lesions only occurred. Therapy was discontinued if regression of noninjected disease also occurred. Six of the 15 patients had regression of at least one injected lesion. Four of these 6 patients also had regression of noninjected disease lasting 4+, 6, 16 and 18+ months. Response was highly related to immune status. Six (83%) of 7 patients who reacted to one of a battery of skin tests responded. All 8 patients who did not react to skin tests failed to respond to therapy. There was no correlation of response with sex, prior therapy, disease-free interval or presence of visceral disease. Mycobacterial CWS and trehalose dimycolate is an effective immunotherapeutic agent. Additional studies of purified immunoadjuvants are warranted.


Safety and adverse reactions in subcutaneous allergen immunotherapy: a review.
Allergen immunotherapy (AIT) is the only treatment which acts on the causes of allergic diseases by modifying their natural history. In the eighties subcutaneous immunotherapy (SCIT) with high biological power allergen extracts caused a number of severe systemic reactions and also fatalities in the UK and the US, resulting in its limitation and in the introduction of other routes of administration. A decisive advance for SCIT safety was understanding that the major cause of mortality was injecting the allergen extract to patients with uncontrolled asthma at the time of injection. This awareness resulted in a significant decrease in fatalities, but not in their abolition. In 2019, an increase in SCIT-related mortality was observed, suggesting to continue the research for still unidentified factors favoring severe reactions, such as the administration of a wrong extract or of allergen doses higher than listed, unintentional intravenous administration, and missed dose reduction after protracted interruption. Moreover, in the context of the improving of the safety, the role played in tolerance-promoting by adjuvants such as CpG oligodeoxynucleotides has to be taken into account, as well as the potential preventive effect performed by the monoclonal anti-IgE antibody omalizumab against the exacerbation of severe reactions during SCIT. The safety of SCIT is good, but the research to improve it further must continue. In particular, the pathophysiological mechanisms related to AIT for inhalants and for Hymenoptera venom should be studied, based on the evident diversity demonstrated by the complete absence of fatal reactions to Hymenoptera venom immunotherapy from its introduction in comparison with the history of serious and fatal offenses examined in this review.


An efficient protocol for the cross-metathesis of sterically demanding olefins.
Cross-metathesis of a wide range of previously unreactive, sterically demanding alkenes can be achieved in fair to excellent yield using a commercially available catalyst by a facile strategy involving reversal of steric preference.


StemBase: a resource for the analysis of stem cell gene expression data.
StemBase is a database of gene expression data obtained from stem cells and derivatives mainly from mouse and human using DNA microarrays and Serial Analysis of Gene Expression. Here, we describe this database and indicate ways to use it for the study the expression of particular genes in stem cells or to search for genes with particular expression profiles in stem cells, which could be associated to stem cell function or used as stem cell markers.


[Analysis of observations entered on medical charts by health care personnel. Activity by the psychiatric team of Mons].
In a service of unselected patients according to diagnosis, prognosis or behaviour, with a large high quality personnel, a daily chart was started where everybody could write notes on patients. There was no imposed or controlled schema. Observations were dropping with time, the critical point being on week 4th. Furthermore, the content of the observations showed that simple descriptions of behaviour were five times more frequent than interpretations. Behavioural descriptions were often precise and understandable for an outsider: three times more descriptive behaviours with precision than vague behaviours. Interpretations, however, looked vague. Difficulties in understanding words and vocabulary were important. To be understood and avoid losing time in self-interpretation, to distinguish truth from false, it was essential to stick to simple expressions, common, but precise.


High expression of HSP90 is associated with poor prognosis in patients with colorectal cancer.
Heat shock protein 90 (HSP90) is a highly conserved chaperone with an approximate molecular weight of 90-kDa. It plays a critical role in maintaining stability and homeostasis of oncoproteins, helping cancer cells living in the unsuitable environmental conditions. The current study aims to inquire the difference of HSP90 expression in tumor tissues and normal tissues, analyze the correlation between HSP90 expression and the prognoses of patients with colorectal cancer (CRC), and investigate its role in CRC preliminarily. Online analysis of HSP90 mRNA levels in different cancers was firstly done in Gene Expression Profiling Interactive Analysis. Then HSP90 expression was determined by immunohistochemistry between 99 CRC tissues and 81 normal tissues. Chi-square test or Fisher's exact test was used to analyze the relationship between HSP90 and histopathologic characteristics. Kaplan-Meier analysis and Cox's proportional hazards model were also done for further analysis of the prognostic values of HSP90. Pearson's correlation coefficients between HSP90 expression values and other mRNA expression values were calculated based on The Cancer Genome Atlas dataset and bioinformatic analysis was done about these screened genes. Colorectal cancer tissues showed significantly higher expression of HSP90 than normal tissues (55.6% vs. 3.7%, P < 0.0001). Kaplan-Meier curves showed high HSP90 expression was associated with poor prognosis (P = 0.039) in CRC patients, and multivariate Cox proportional hazards regression model analysis also indicated that HSP90 expression (HR = 1.930, 95% CI [1.113-3.349], P = 0.019) linked to poor prognosis. Moreover, 85 genes were correlated with HSP90, which were involved in metabolic process and enriched in pathways of Proteasome and Base excision repair. Our results suggested that HSP90 expression is inversely associated with survival outcomes and could be an independent prognostic factor for CRC patients. It mainly involved in metabolic process and exerted binding and catalytic activities.


[Validation of the Acoustic Voice Quality Index in the Russian language].
Of this study was to validate the Acoustic Voice Quality Index (AVQI) in Russian language and determine threshold values to differentiate normal and dysphonic voices in russophone population. 41 recordings of patients with laryngeal hemiplegia and hemiparesis appeared after thyroid carcinomas' surgical treatment and laryngeal cancer from the Tomsk Cancer Research Institute were used, as well as 10 new recordings of normophonic people, composing a control group. Voice samples included the first quatrain of the poem «Sail» written by M.Yu. Lermontov, and sustained vowel «a». Four specialists who work with voice disorders (three speech-language pathologists and one phoniatrist) rated degree of dysphonia for all voice sample. Moreover, the AVQI was calculated for each sample. There was a statistically significant correlation between auditory-perceptual assessment and the AVQI (r=0.74), this confirms that AVQI is effective in evaluating voice disorders. The group of people with normal voice had relatively low values of AVQI, whereas the group of patients with laryngeal diseases had relatively high values. Analysis of ROC-curve showed that AVQI has excellent diagnostic accuracy to differentiate normal and dysphonic voices (AUC=0.966). The AVQI is the excellent tool for objective assessment of voice disorders in the Russian population/.


N alpha-alkylated derivatives of 2-phenylhistamines: synthesis and in vitro activity of potent histamine H1-receptor agonists.
New potent N alpha-alkylated histamine H1-receptor agonists have been prepared and functionally evaluated for partial agonist potency and selectivity. N alpha-Methyl-2-(3-trifluoromethylphenyl)histamine contracts ileal segments and aortic rings of guinea-pig with a relative potency of 174% (95% confid. lim. 161-188%) and 217% (164-287%), respectively (histamine: 100%) and is the most potent H1 receptor agonist described so far.


Cardioprotective Role of Estrogen in Takotsubo Cardiomyopathy.
Takotsubo cardiomyopathy (TC) is a rare, reversible cause of left ventricular wall motion abnormality (LVWMA) that mimics the presentation of acute myocardial infarction (AMI). TC is usually preceded by an emotional or physical stressor and appears to be more common in postmenopausal women. Various pathophysiological hypotheses of TC have been proposed, but the exact mechanism of action remains elusive. Elevated levels of catecholamines leading to cardiac dysfunction are the most prevalent hypothesis. The protective role of estrogen in the development of cardiomyopathies has been studied extensively. International Takotsubo Diagnostic Criteria (InterTAK) and Mayo clinic diagnostic criteria both have the stipulation stating prevalence of TC is higher in postmenopausal women which hints towards the protective role of estrogen in the development of TC. To review the protective role of estrogen in the mechanism of this novel pathology, we searched Pubmed and Google scholar for the relevant articles by using keywords such as: "takotsubo cardiomyopathy", "apical ballooning", "broken heart syndrome", "stress cardiomyopathy", "left ventricle wall motion abnormality", "estrogen", "estradiol" and "sex hormones". Our research revealed that although the prevalence of TC is greater in postmenopausal women as compared to men, the prognosis is worse in men. It also revealed the involvement of multiple cellular pathways under the influence of estrogen that could explain the cardioprotective effect of estrogen. Most of the articles found were based on animal studies, thus, there is an emphasis on future human studies. However, we strongly suggest evaluating estrogen levels as part of the initial workup for any patient presenting with signs and symptoms of cardiac pathology.


Nonspecific protein adsorption on cationically modified Lyocell fibers monitored by zeta potential measurements.
Nonspecific protein deposition on Lyocell fibers via a cationization step was explored by adsorption of two different N,N,N-trimethyl chitosan chlorides (TMCs). Both, the cationization and the subsequent protein deposition steps were performed and monitored in situ by evaluating the zeta potential using the streaming potential method. Both employed TMCs (degree of substitution with N+Me3Cl groups: 0.27 and 0.64) irreversibly adsorb on the fibers as proven by charge reversal (-12 to +7mV for both derivatives) after the final rinsing step. Onto these cationized fibers, BSA was deposited at different pH values (4, 5, and 7). Charge titrations revealed that close to the isoelectric point of BSA (4.7), BSA deposition was particularly favored, while at lower pH values (pH 4), hardly any adsorption took place due to electrostatic repulsion of the cationic fibers and the positively charged BSA. This work sets the foundation for further investigations to use zeta potential measurements for protein adsorption studies on fibrous materials.


Assessing minimal residual disease (MRD) in leukemia: a changing definition and concept?
The term minimal residual disease (MRD) in its currently accepted application refers to low-level disease detected in a whole variety of clinical situations. It is used to describe residual disease after suboptimal induction chemotherapy, but at the same time refers to the lowest levels of disease potentially compatible with cure or to molecularly defined relapse after long-term remission. This discussion intends to redefine MRD into some biologically relevant subcategories which may warrant their own independent terminology.


Adverse Events in Cancer Immunotherapy.
Cancer immunotherapy has resulted in durable responses in patients with metastatic disease, unseen with traditional chemotherapy. Several therapies have been approved by the Food and Drug Administration for the treatment of various cancers, including: immune checkpoint inhibitors, cytokines - interleukin 2 (IL-2) and interferon alpha (IFN), and the cancer vaccine sipuleucel-T. These therapies upregulate the immune system to enhance antitumor responses. As a consequence, they can cause inflammatory and immune-related adverse events that can affect one or more organs, can be serious, and on occasion lifethreatening. The management of these adverse events is complex, and requires a multidisciplinary approach involving not only oncologists, but also other internal medicine specialists, to ensure prompt diagnosis and optimal management of these complications.


PET in the Diagnostic Management of Soft Tissue Sarcomas of Musculoskeletal Origin.
Soft tissue sarcomas (STSs) account for less than 1% of adult solid tumors and about 7% of pediatric malignancies, causing 2% of cancer-related deaths. With the advent of PET-computed tomography (CT), the value of (18) fluorine-2-fluoro-2-deoxy-d-glucose (FDG) PET imaging to improve the management of STSs has been explored. FDG PET imaging has been found useful in restaging and treatment response assessment. This article reviews current knowledge and application of FDG PET-CT in initial diagnosis, staging, restaging, treatment response monitoring, and prognosis, with a brief overview of the most common histologic subtypes of STS.


Impact of Antimicrobial-Resistant Bacterial and Polymicrobial Infection on Wound Healing After Minor Forefoot Amputation in Chronic Limb-Threatening Ischemia With Infection.
This study aimed to evaluate the relationship between bacteriological findings and wound healing after minor amputation in the treatment of chronic limb-threatening ischemia (CLTI) with infection. This single-center retrospective study analyzed 135 consecutive limbs with tissue loss and infection from 120 patients who underwent endovascular therapy (EVT) and minor forefoot amputation for CLTI with wound infection between November 2017 and August 2021. The Kaplan-Meier method was used to assess the rate of wound healing after the procedure. The Cox proportional-hazards model was used to examine the impact of bacteriological findings and baseline characteristics on wound healing. The wound healing rate at 6 months was 72.6%. In a multivariate analysis, in addition to hemodialysis (hazard ratio [HR]=1.73; p=0.009) and amputation above the metatarsophalangeal (MP) joint (HR=1.81; p=0.006), antimicrobial-resistant bacterial infection (HR=1.80, p=0.004) and polymicrobial infection (H=1.51; p=0.049) were predictors of delayed wound healing. Antimicrobial-resistant bacterial infection, polymicrobial infection, hemodialysis, and amputation above the MP joint were independent predictors of delayed wound healing after EVT and minor forefoot amputation in patients with CLTI and bacterial wound infection. In this single-center retrospective study, we analyzed 136 consecutive limbs with tissue loss and infection from 120 patients who underwent endovascular therapy and minor forefoot amputation for chronic limb-threatening ischemia (CLTI) with wound infection between November 2017 and August 2021. Our main findings were that antimicrobial-resistant bacterial infection, polymicrobial infection, hemodialysis, and amputation above the metatarsophalangeal joint were independent predictors of delayed wound healing after minor amputation. This is the first report of the association between bacteriological studies and wound healing in CLTI with infection, and will be of great help in the future clinical practice.


Relative influences of tumor volume before surgery and the cytoreductive outcome on survival for patients with advanced ovarian cancer: a prospective study.
The purpose of this study was to determine the relative influences of the extent of disease present before surgery and completeness of cytoreduction on survival for patients with advanced ovarian cancer. Patients (408) with stage IIIC epithelial ovarian cancer had cytoreductive surgery before systemic platinum-based combination chemotherapy. A ranking system (0-3) was devised to prospectively quantify the extent of disease involving: (1) right upper quadrant (diaphragm/hepatic, and adjacent peritoneal surfaces), (2) left upper quadrant (omentum/gastro-colic ligament, spleen, stomach, transverse colon, splenic flexure of colon), (3) pelvis (reproductive organs, recto-sigmoid, pelvic peritoneum), (4) retroperitoneum (pelvic/aortic nodes), and (5) central abdomen (small bowel, ascending/descending colon, mesentery, anterior abdominal wall, pericolic gutters). Survival was analyzed (log rank and Cox regression) on the basis of the rankings at these anatomic regions, the sum of intraabdominal rankings, and the cytoreductive outcome. Overall median and estimated 5-year survivals were 58.2 months and 49%. On univariate analysis, the central abdominal (P = 0.008) and left upper quadrant (P = 0.03) rankings, the sum of rankings (P = 0.01), and the cytoreductive outcome (P </= 0.0001) influenced survival (log rank). Survival was independently (stepwise Cox model) influenced by the sum of rankings (0-5, RR 1.00; 6-10, RR 1.24; 11-15, RR 1.44; P = 0.05), and completeness of cytoreduction (visibly disease-free, RR 1.00; </=1 cm residual, RR 2.32; >1 cm residual, RR 2.98; P = 0.001). Cytoreduction to a visibly disease-free outcome has a more significant influence on survival than the extent of metastatic disease present before surgery. Operative efforts should not be abbreviated on the hypothesis that extensive disease at specific anatomic regions precludes long-term survival.


Effective Technique for Pancreas Transplantation by Iliac Vascular Transposition, Without Heparin-Based Anticoagulation Therapy.
To evaluate patients undergoing a new procedure, iliac vascular transposition, in pancreas transplantation regarding the risk of thrombosis and graft survival without heparin-based anticoagulation therapy. Iliac vascular transposition (IVT) involves changing the positions of the external iliac artery and vein relative to each other. In this study, this technique was evaluated in patients undergoing the procedure compared with patients not undergoing the procedure (iliac vascular parallel (IVP) group). No patients received prophylactic heparin therapy. Two patients in the IVP group (n = 26) developed complete thrombosis and six developed partial thrombosis, compared with no patients with complete thrombosis and one with partial thrombosis in the IVT group (n = 29). The cumulative incidence of thrombosis was significantly higher in the IVP group (p < 0.01). Cox regression revealed that not receiving iliac vascular transposition was the only significant risk factor for thrombosis (odds ratio: 10.1, 95% confidence interval: 1.27-81.2; p = 0.03). One-year graft survival was significantly better in the IVT group vs IVP group (p = 0.03). IVT in pancreas transplantation is a simple technique that results in a lower thrombosis risk and better graft survival rates without heparin-based anticoagulation therapy.


Extrapyramidal side effects in chlorpromazine recipients: emergence according to benztropine prophylaxis.
The frequency of extrapyramidal symptoms (EPS) attributed to chlorpromazine among 86 patients who received benztropine for the prevention of EPS (9.3%) was similar to that of the 568 patients who received chlorpromazine alone (10.6%). The data in this small sample indicated that the prophylactic use of benztropine had no effect in reducing the rate of EPS.


Synthesis and blood-schizontocidal antimalarial activities of 2-substituted/2,5-disubstituted-8-quinolinamines and some of their amino acid conjugates.
Thirteen new analogues (32-40, 45-48) of recently discovered potent blood-schizontocidal antimalarial agent, 2-tert-butylprimaquine (2) are synthesized and evaluated for in vivo antimalarial activities against drug-sensitive P. berghei strain and multi-drug resistant P. yoelii nigeriensis strain. Two of the amino acid conjugates (47-48) have exhibited potent antimalarial activities similar to that of 2 against both drug-sensitive and multi-drug resistant strains.


Cytogenetic analysis of embryos generated from in vitro matured mouse oocytes reveals an increase in micronuclei due to chromosome fragmentation.
(i) To determine the prevalence of micronuclei in the cytoplasm of embryos generated from in vitro matured oocytes. (ii) Assess whether micronuclei presence are the result of chromosome fragmentation or the loss of whole chromosomes. In vitro fertilization was performed on mature oocytes generated from superovulated mice (control) and in vitro matured mouse oocytes. Fertilized oocytes were cultured to the two-cell stage and fixed to slides. Micronuclei assessment was performed after staining with Giemsa. Centromere assessment was made using immunofluorescent staining (CREST) of the centromeric kinetochores. Micronuclei were observed in 2% (4/197) of control two-cell embryos and 36.2% (46/127) of two-cell embryos generated from in vitro matured oocytes (P < 0.02). Centromeres were not detected in micronuclei from either group. A significant increase in micronuclei was observed in embryos generated from in vitro matured oocytes. The lack of accompanyingcentromeres would suggest the micronuclei are the result of chromosome fragmentation.


Zika virus vertical transmission in interferon receptor1-antagonized Rag1-/- mice results in postnatal brain abnormalities and clinical disease.
The mechanisms by which vertically transmitted Zika virus (ZIKV) causes postnatal brain development abnormalities and congenital disease remain poorly understood. Here, we optimized the established anti-IFNAR1 treated, Rag1-/- (AIR) mouse model of ZIKV infection to examine the consequence of vertical transmission on neonate survival and postnatal brain development. We found that modulating the infectious dose and the frequency of anti-IFNAR1 treatment of pregnant mice (termed AIRlow mice) prolonged neonatal survival allowing for pathogenesis studies of brain tissues at critical postnatal time points. Postnatal AIRlow mice all had chronic ZIKV infection in the brain that was associated with decreased cortical thickness and cerebellar volume, increased gliosis, and higher levels of cell death in many brain areas including cortex, hippocampus and cerebellum when compared to controls. Interestingly, despite active infection and brain abnormalities, the neurodevelopmental program remained active in AIRlow mice as indicated by elevated mRNA expression of critical neurodevelopmental genes in the brain and enlargement of neural-progenitor rich regions of the cerebellum at a developmental time point analogous to birth in humans. Nevertheless, around the developmental time point when the brain is fully populated by neurons, AIRlow mice developed neurologic disease associated with persistent ZIKV infection in the brain, gliosis, and increased cell death. Together, these data show that vertically transmitted ZIKV infection in the brain of postnatal AIRlow mice strongly influences brain development resulting in structural abnormalities and cell death in multiple regions of the brain.


Effect of postnatal treadmill exercise on c-Fos expression in the hippocampus of rat pups born from the alcohol-intoxicated mothers.
Maternal alcohol-intoxication during pregnancy exerts detrimental effects on fetal development and is known to influence learning ability and memory capability by altering neuronal activity in the hippocampus. c-Fos expression represents neuronal activity and plays a crucial role in the brain development. Physical exercise is known to enhance neuronal plasticity and activity. In the present study, we investigated the influence of postnatal treadmill running on the c-Fos expression in the hippocampus of rat pups born from the alcohol-intoxicated mothers. The results obtained show that maternal alcohol-intoxication suppressed c-Fos expression in the hippocampus of rat pups and that postnatal treadmill exercise enhanced c-Fos expression in the hippocampus of these rat pups. The present study suggests that exercise should be considered as a therapeutic means of countering the effects of maternal alcohol-intoxication, and that it may provide a useful strategy for enhancing the neuronal activity of children born from the mothers who abuse alcohol during pregnancy.


Catalytic and activating protons follow different pathways in the H(+)-ATPase of potato tuber mitochondria.
The effect of some F0F1 inhibitors on the activation of the H(+)-ATPase by the electrochemical proton gradient was investigated in mitochondria extracted from potato tubers. Transient activated state of the ATPase was revealed by addition of ATP and of the detergent lauryldimethylamine oxide (LDAO) to energized mitochondria. Venturicidin, tri-n-butyltin and aurovertin at high concentrations did not affect the process of delta mu H(+)-activation, whereas oligomycin fully blocked it. The results support the idea of separate pathways or binding sites for catalytic and activating protons.


A search for genetic markers associated with egg production in the ostrich (Struthio camelus).
The aim of the current study was to search for genetic markers, microsatellite loci associated with laying performance in ostriches. The material consisted of two groups of ostrich hens characterized by high or low laying performance (over 75 and less than 25 eggs per season, respectively). The investigation covered 30 microsatellite loci characteristic for the ostrich (the CAU group) and led to identification of significant differences in allele and genotype frequencies between the two groups of hens considered. Out of a total of 30 microsatellite loci examined, 28 showed different alleles in relation to analyzed performance groups. In hens of high laying performance (HP group, n = 12), specific alleles occurred in 23 microsatellite loci (40 alleles of 243 identified), while in those of low egg production (LP group, n = 12), they occurred in 22 (51 alleles of 243 identified). The results indicate the usefulness of the microsatellite loci as the potential genetic markers associated with laying performance that can be applied for genetic improvement of ostrich flocks.


Antitumor agents. Part 186: Synthesis and biological evaluation of demethylcolchiceinamide analogues as cytotoxic DNA topoisomerase II inhibitors.
Demethylation of colchiceinamide (2) and its analogues (3-10) afforded a novel class of mammalian DNA topoisomerase II inhibitors (2a-10a) without displaying tubulin inhibitory activity. All target compounds inhibited the catalytic activity of topoisomerase II at drug concentrations at 100 microM. An in vitro cytotoxicity assay indicated that compounds 3a and 8a were strong and tissue-selective cytotoxic agents against the MCF-7 breast cancer cell line (IC50 = 0.36 and 0.48 microgram/mL, respectively) and the CAKI-1 renal cancer cell line (IC50 = 0.72 and 0.96 microgram/mL, respectively).


Plasma Calprotectin Is Predictive for Short-Term Functional Outcomes of Acute Ischemic Stroke.
Blood-based prognostic biomarkers of acute ischemic stroke (AIS) are limiting. Calprotectin is suggested to be involved in directing post-stroke inflammatory conditions. However, the pathological alteration of circulating calprotectin in AIS is yet to be thoroughly elucidated. Therefore, this study aimed to investigate the levels and clinical relevance of calprotectin in AIS. This study recruited 271 patients with AIS within 24 h since symptom onset and 145 non-stroke healthy controls (HC) from February 1, 2018, to Dec 31, 2020. Patients were followed up for 2 weeks for observation of functional outcomes, as determined by the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). Plasma calprotectin concentrations were determined by ELISA. Plasma calprotectin concentrations were significantly higher in patients with AIS compared with controls [patients vs. control: median (IQR) 54.2 (39.01-99.04) vs. 50.04 (35.42-61.22), p < 0.001]. Besides, patients with poor prognosis, as defined by mRS ≥ 3, had significantly higher calprotectin levels than patients with good prognosis [poor prognosis patients vs. good prognosis patients: median (IQR) 61.99 (47.52-108) vs. 43.36 (33.39-60.2), p < 0.001]. Plasma calprotectin levels were positively associated with the disease severity of AIS, as reflected by infarction volume and NIHSS score at baseline. Furthermore, baseline calprotectin was found to be independently associated with poor prognosis [odds ratio (OR): 1.02, 95% CI: 1.01-1.03] and disease progression (OR: 1.03, 95% CI: 1.02-1.04) of AIS during a 2-week follow-up, with adjustment of possible confounding factors. Plasma calprotectin is associated with short-term functional outcomes of AIS.


The influence of soil characteristics on the extractability of Cd, Pb and Zn in upland and moorland soils.
A study was undertaken to investigate the feasibility of using existing data sets of total soil metal concentrations and soil parameters, such as pH, to predict available metal concentrations on a regional or national basis. The attraction of such an approach is that it would provide valuable data for initiatives requiring information on the availability and mobility of metals in soils without the need for costly soil sampling and analysis. Ninety-seven topsoil and subsoil samples were collected from 6 soil series in a catenary sequence in north Wales to provide data for the development of an empirical model. These were analysed for total, 0.01 M CaCl2-extractable and porewater metal concentrations and for a range of soil properties including pH, solid and dissolved organic matter and cation exchange capacity. Regression analysis showed that, of the soil parameters measured, pH was the most important predictor variable for the estimation of CaCl2-extractable Cd, Pb and Zn. pH accounted for up to 86% of the variance in the proportion of 'total' metals which were extracted by CaCl2, a reagent that is commonly used to estimate plant uptake of elements. However, the relationships recorded between soil parameters and Kd (total metal/porewater metal) were much weaker, indicating that porewater metal concentrations can less readily be predicted from total soil metal concentrations and soil properties.


Plant Responses and Tolerance to Salt Stress: Physiological and Molecular Interventions.
Salinity is considered one of the most devastating environmental stresses that drastically curtails the productivity and quality of crops across the world [...].


The Resolution Rate of Pulmonary Embolism on CT Pulmonary Angiography: a Prospective Study.
To prospectively assess the rate of clot resolution from CT pulmonary angiography (CTPA) in patients with acute pulmonary embolism (PE). This prospective cohort study included 290 patients (136 men, 154 women; mean age, 51.9 years) with acute PE. All patients had a CTPA at the presentation and had at least one follow-up within 6 months (mean 72.7 days). Sixty-four percent of patients had follow-up scans for research purposes within a pre-determined period (between 28 and 184 days; mean, 78.27 days) and 36 % had (between 2 and 184 days; mean, 62.78 days) for a clinical indication. The volume of each clot was measured using a semi-automated quantification program. The resolution rate was evaluated by interval-censored analysis. The overall estimated probability of complete resolution was 42 % at 7 days, 56 % at 10 days, and 71 % at 45 days. Achieving complete resolution was significantly faster in patients with peripheral clots (HR: 1.78; CI: 1.05-3.03, p = 0.032) but slower in patients with consolidation and history of venous thromboembolism (VTE), (HR: 0.37; CI: 0.18-0.79, p = 0.01 and HR: 0.57; CI: 0.35-0.91, p = 0.019, respectively). Although the patients with cancer showed a faster resolution rate (HR: 1.67; CI: 1.05-2.68, p = 0.032), the mortality rate was significantly higher than non-cancer patients. The resolution rate of clot burden in acute PE was associated with patients' clinical presentation variables and CTPA imaging biomarkers. This information may be incorporated into designing a prediction rule and determining the appropriate duration of anticoagulation therapy in patients with acute PE.


Aspartic acid substitutions in monoamine oxidase-A reveal both catalytic-dependent and -independent influences on cell viability and proliferation.
Post-translational influences could underlie the ambiguous roles of monoamine oxidase-A (MAO-A) in pathologies such as depression, cancer and Alzheimer disease. In support of this, we recently demonstrated that the Ca²⁺-sensitive component of MAO-A catalytic activity is inhibited by a pro-survival p38 (MAPK)-dependent mechanism. We substituted three aspartic acid (D) residues in human MAO-A that reside in putative Ca²⁺-binding motifs and overexpressed the individual proteins in the human HEK293 cell line. We assayed the overexpressed proteins for catalytic activity and for their influence on cell viability (using MTT conversion and trypan blue exclusion) and proliferation/DNA synthesis [using bromodeoxyuridine (BrdU) incorporation]. Innate MAO-A catalytic activity (and the capacity for generating hydrogen peroxide) was unaffected by the D61A substitution, but inhibited moderately or completely by the D248A and D328G substitutions, respectively. The Ca²⁺-sensitive activities of wild-type and D248A MAO-A proteins were enhanced by treatment with the selective p38(MAPK) inhibitor, SB203580, but was completely abrogated by the D61A substitution. Monoamine oxidase-A(D61A) was toxic to cells and exerted no effect on cell proliferation, while MAO-A(D248A) was generally comparable to wild-type MAO-A. As expected, the catalytic-dead MAO-A(D328G) was not cytotoxic, but unexpectedly enhanced both MTT conversion and BrdU staining. Variant-dependent changes in Bax and Bcl-2/Bcl-XL protein expression were observed. A different pattern of effects in N2-a cells suggests cell line-dependent roles for MAO-A. A catalytic-dependent mechanism influences MAO-A-mediated cytotoxicity, whereas a catalytic-independent mechanism contributes to proliferation. Context-dependent inputs by either mechanism could underlie the ambiguous pathological contributions of MAO-A.


Pre-clinical evaluation of a new orally-active CCK-2R antagonist, Z-360, in gastrointestinal cancer models.
Gastrin has a role in gastrointestinal (GI) malignancy. This study provides pre-clinical evaluation of a novel, orally-active gastrin/cholecystokinin-2 receptor (CCK-2R) antagonist, Z-360. (125)I gastrin-17 (G17) displacement and G17-stimulated calcium assays were used in classical CCK-2R-transfected cell lines. Akt phosphorylation was assessed by Western blotting. Z-360 efficacy in vivo was evaluated in three human xenograft models, and microvessel density and apoptosis in these models were investigated by immunohistochemistry. Z-360 inhibited (125)I G17 binding to cells expressing CCK-2R, and G17-stimulated signalling. Reduced Akt phosphorylation in an oesophageal cell-line treated with Z-360 was reversed by co-treatment with G17. Z-360 increased survival in a gastric ascites model (p=0.011) and decreased tumour growth in a hepatic metastasis model (81%, p=0.02). In an orthotopic pancreatic model, Z-360 combined with gemcitabine decreased final tumour weight compared to single agents (84%, p=0.002) and there was increased apoptosis and decreased microvessel density in ex vivo tumour tissue. These results show that the orally-active CCK-2R antagonist, Z-360 has high sub-nM affinity for classical CCK-2R, is well tolerated in vivo and exerts an anti-tumour effect.


Current insight into diagnostics and pathophysiology of the antiphospolipid syndrome.
The diagnosis of the antiphospholipid syndrome, a non-inflammatory autoimmune disease characterized by thrombosis or pregnancy morbidity in the presence of antiphospholipid antibodies, depends greatly upon laboratory diagnostics. The diagnostic value of all available assays to detect antiphospholipid antibodies and the anticardiolipin assay in particular, is a matter of ongoing debate. Although the presence of lupus anticoagulant correlates best with thrombosis, accurate determination is not always possible due to anticoagulant treatment. Data on the predictive value of alternatives such as the anti-beta2-glycoprotein I and the anti-prothrombin antibody assay are insufficient and prospective cohort studies are needed. Determining antiphospholipid antibody profiles seems to increase diagnostic specificity. Substantial progress has been made in unravelling the pathophysiological mechanisms underlying the antiphospholipid syndrome. Several cellular receptors for antibody-beta2-glycoprotein I complexes have been identified and their roles in cellular activation are being investigated. In vivo data should provide more insight into the importance of the interaction with individual receptors.


IgG4 Disease-Related Ataxia.
We describe a male patient presenting with cerebellar ataxia and behavioural frontotemporal dementia in whom imaging showed cerebellar atrophy. He had significantly low N-acetyl aspartate to creatine (NAA/Cr) area ratio on MR spectroscopy of the cerebellum, primarily affecting the vermis. CT body scan showed extensive abnormal tissue within the mesentery, the retroperitoneum and perinephric areas. PET-CT showed increased tracer uptake within the wall of the aorta suggestive of an aortitis and within the perinephric tissue bilaterally. Biopsy of the perinephric tissue confirmed IgG4 disease. Treatment with steroids and mycophenolate improved his clinical state, but he developed symptoms attributed to pericardiac effusion that necessitated treatment initially with drainage and subsequently with pericardial window. After a course of rituximab, he had an episode of sepsis that did not respond to appropriate treatment and died as a result. Both the imaging findings and neurological presentation with cerebellar ataxia and behavioural frontotemporal dementia are novel in the context of IgG4 disease.


Non-linear pattern of age-specific bone mineral density and related factors in women: data from the 5th Korea National Health and Nutrition Examination Survey.
Age-specific bone mineral density (BMD) of Korean women showed a nonlinear pattern. According to our study, this pattern could be mainly attributed to the nonlinear effects of body composition. Interventions targeting these factors in premenopausal women could be critical for achieving peak BMD. The patterns of age-specific bone mineral density (BMD) of femur and spine in women showed a non-unidirectional decrease, with ups and downs around the point of achieving peak BMD, that are not evident in men. We investigated the factors associated with these age-specific BMD in women using linear and nonlinear models. A total of 4681 women recruited during the 5th Korean National Health and Nutrition Examination Survey 2010-2011 (KNHANES V) were included. A range of related factors were considered including body compositional, reproductive, and socio-behavioral factors. Age-specific BMD was demonstrated using a generalized additive model (GAM) with smoothing spline transformation. Age, lean body mass, fat mass, and age at menarche were significant predictors of BMD in premenopausal women. The GAM plot of BMD according to age revealed two peaks for total femur, femoral neck, and lumbar spine. After adjustment for body compositional factors, the peaks flattened. In the full model, the pattern for lumbar spine showed a single peak around the mid-40s. The GAM showed a generally better performance than the linear model for BMD at all three sites. Reduced models that included only lean body mass and fat mass best explained the variance of BMD in GAMs. The BMD of Korean women in reproductive period could be largely attributed to the nonlinear effects of age and body compositional factors. Intervention targeting these factors could be critical for maintaining peak BMD.


Molecular and Morphological Characterization of Introgression Lines with Resistance to Bacterial Leaf Blight and Blast in Rice.
The present study evaluates marker assisted forward breeding (MAFB)-derived disease resistant introgression lines (ILs) which do not have the targeted resistance genes for bacterial blight (xa5 + xa13 + Xa21) and blast (Pi2 + Pi9 + Pi54). The ILs were derived in the background of two elite rice cultivars, Krishna Hamsa [Recurrent Parent 1 (RP1)] and WGL 14 (RP2), involving multi-parent inter-crossing. Molecular characterization with gene specific markers for seven reported resistance genes each for bacterial blight (Xa33, Xa38, xa23, Xa4, xa8, Xa27 and Xa41) and blast (Pi1, Pi20, Pi38, Pib, Pitp, Pizt and Pi40) revealed the presence of xa8 and Xa38, in addition to the targeted xa5, xa13 and Xa21 for bacterial blight resistance and Pi1, Pi38, Pi40, Pi20, Pib and Pipt, in addition to the targeted Pi9 and Pi54, for blast resistance in various combinations. A maximum of nine resistance genes xa5 + Xa21 + Pi54 + xa8 + Pipt + Pi38 + Pi1 + Pi20 + Pib was observed in RP1-IL 19030 followed by eight genes xa5 + xa13 + Xa21 + xa8 + Pi9 + Pipt + Pi1 + Pi20 in two RP2-ILs, 19344 and 19347. ANOVA revealed the presence of significant variability for all the yield traits except "days to 50% flowering" (DFF). Box plots depicted the seasonal differences in the phenotypic expression of the yield traits. There was significant positive association of grain yield with days to flowering, tiller number and panicle number. Thousand grain weight is also significantly and positively correlated with grain yield. On the contrary, grain yield showed a significantly negative association with plant height. Multi-parent selective inter-crossing in the present study not only led to the development of high yielding disease resistant ILs but also enhanced recovery of the recurrent parent via selection for essential morphological features. More than 90.0% genetic similarity in the ILs based on SNP-based background selection demonstrated the success of multi-parent selective intercrossing in the development of disease resistant NILs.


Effects of intrauterine infusion of bacterial lipopolysaccharides on the mammary gland inflammatory response in goats.
This study aimed to determine if intrauterine-infused lipopolysaccharides (LPS) can be translocated to the mammary glands and induce an inflammatory response. Thirty-seven goats were divided into two experiments. Nineteen goats (control group, n = 9; LPS group, n = 10) were subjected to intravenous injection of LPS, and eighteen goats (control group, n = 8; LPS group, n = 10) were subjected to intrauterine infusion of LPS. Milk and blood samples were collected before and after the LPS challenge, to measure the blood leukocyte count (BLC), plasma LPS-binding protein (LBP), milk yield, milk somatic cell count (SCC), lactoferrin (LF), milk lactoperoxidase (LPO) activity, and pro- and anti-inflammatory cytokines in plasma and milk. Mammary gland tissues were collected from the parenchyma before and after the LPS challenge, for immunohistochemistry of LPS. In the intravenous injection experiment, the BLC (P < 0.001) and milk yield (P = 0.009) were lower, whereas the LF concentration (P < 0.001) and milk LPO activity (P < 0.001) were higher in the LPS group compared to that in the control group. LPS was detected in the mammary gland 3 and 24 h after intravenous injection of LPS. In the intrauterine infusion experiment, the mean concentrations of IL-1β and IL-6 in milk were higher in the LPS group compared to that in the control group (P = 0.004 and P = 0.017, respectively), whereas there were no changes in milk yield or SCC. LPS was detected in the connective tissues and interepithelial spaces of the alveoli of the mammary glands 24 h after intrauterine infusion of LPS. We conclude that intrauterine-infused LPS can be translocated to the mammary glands from the uterus, however, the amount of translocated LPS might not be enough to induce symptoms of clinical or subclinical mastitis.


Effects of programmed cell death protein 10 on the Schistosoma japonicum female reproductive system.
This study aimed to investigate the effects of programmed cell death protein 10 (PCDP10) on the female reproductive system of Schistosoma japonicum, one of the major infectious agents of schistosomiasis. We found that PCDP10 was widely distributed in the integument, the worm parenchymal area, and the vitellarium of the female worm, but was localized to a lesser extent in the ovary and testicles. RNAi experiments successfully achieved gene knockdown, and the ultrastructural morphology of the adult reproductive organs was observed. The results demonstrated that, compared with those of the negative control group, the number of cortical granules around oocytes decreased and the number of immature oocyte cells increased. Fusion of yolk globules occurred, and the number and the diameter of yolk droplets decreased significantly. Real-time PCR showed that the expression of yolk glands reached its peak before ovulation and then decreased. The TUNEL assay results showed that apoptosis in the RNAi group was significantly higher than that in the negative control group. These results suggested that SjPCDP10 plays an important role in the female reproductive system. In conclusion, PCD10 is involved in oocyte growth and development, especially in eggshell formation, which may provide a reference for further elucidating the molecular mechanism of PCDP10 involved in egg formation and embryo development in Schistosoma japonicum.


Third trimester messenger RNA COVID-19 booster vaccination upsurge maternal and neonatal SARS-CoV-2 immunoglobulin G antibody levels at birth.
BNT162b2 messenger RNA (mRNA) COVID-19 vaccine administered during pregnancy was found to produce a strong maternal immunoglobulin (IgG) response which crosses the placenta to the newborn. Our aim was to evaluate maternal and neonatal SARS-CoV-2 IgG antibody levels at birth, following a COVID-19 booster vaccine during the third trimester. A prospective cohort study including women admitted to delivery ward at least 7 days after their BNT162b2 (Pfizer/BioNTech) booster vaccination without a prior clinical COVID-19 infection. SARS-CoV-2 IgG antibodies levels were measured in maternal blood upon admission to delivery and in the umbilical blood within 30 min following delivery. The correlation between antibody titers, feto-maternal characteristics, maternal side effects following vaccination, and time interval from vaccination to delivery were analyzed. Between September to November 2021, high antibody levels were measured in all 102 women and 93 neonatal blood samples, at a mean ± standard deviation duration of 7.0 ± 2.9 weeks after the third vaccine. We found positive correlation between maternal and neonatal antibodies (r = 0.73, 95% confidence interval [CI] 0.61 to 0.81, p < 0.001), with neonatal titers approximately 1.4 times higher compared to maternal titers. In the multivariable analysis maternal antibody levels dropped by -7.2% (95% CI -12.0 to -2.3%, p = 0.005) for each week that passed since the receipt of the third vaccine dose. In contrary, systemic side effects after the third vaccine were associated with higher maternal antibody levels of 52.0% (95% CI 4.7 to 120.8%, p = 0.028). Also, for each 1 unit increase in maternal body mass index, maternal antibody levels increased by 3.6% (95% CI 0.4 to 6.9%, p = 0.025). BNT162b2 mRNA COVID-19 booster dose during the third trimester of pregnancy was associated with strong maternal and neonatal responses as reflected by maternal and neonatal SARS-CoV-2 IgG antibody levels measured at birth. These findings support the administration of the COVID-19 booster to pregnant women to restore maternal and neonatal protection during the ongoing pandemic.


Shifting human salty taste preference: Potential opportunities and challenges in reducing dietary salt intake of Americans.
Dietary salt reduction of Americans has been a focus of public health initiatives for more than 40 years primarily due to the association between high salt intake and development of hypertension. Despite past efforts, salt intake of Americans has remained at levels well above dietary recommendations, likely due in part to the hedonic appeal of salty taste. As such, in 2010 the Institute of Medicine suggested a strategy of gradual salt reduction of processed foods, the primary source of Americans' dietary salt intake, via an approach intended to minimize impact on consumer acceptability of lower-sodium foods. This brief review discusses the ontogeny and development of human salt taste preference, the role of experience in shifting salt preference, and sources of dietary salt. Our current understanding of shifting human salt taste preference is discussed within the context of potential opportunities for success in reducing dietary salt, and gaps in the research that both limit our ability to predict effectiveness of gradual salt reduction and that need be addressed before a strategy to shift salt preference can realistically be implemented.


Fe3+-ensemble of triazole appended pentacenequinone derivative for "turn-on" detection of fluoride ions.
Triazole appended pentacenequinone derivative 6 has been synthesized by Suzuki-Miyaura coupling protocol. Compound 6 exhibits selective response towards Fe(3+) ions. Interestingly 6.Fe(3+) ensemble exhibits "turn-on" response towards fluoride ions and thus, makes the 6.Fe(3+) ensemble a novel probe for the selective detection of fluoride ions. Further, derivative 6 coated test strip can detect traces of Fe(3+) and F(-) ions and provide a simple, portable and low cost method for detection of Fe(3+) and F(-) ions in aqueous solution.


The Mayo Endoscopic Score Is a Novel Predictive Indicator for Malignant Transformation in Ulcerative Colitis: A Long-Term Follow-Up Multicenter Study.
Data on the relative risk of malignant transformation in ulcerative colitis (UC) are insufficient. We investigated the potential value of the Mayo endoscopic score (MES) for predicting malignant transformation in patients with UC. Data of patients with UC evaluated at our institute from June 1986 to December 2019 were retrospectively analyzed. The MES used in the study indicated the results of the first colonoscopy after hospitalization. We defined MES of 0-1 as low and MES of 2-3 as high. Univariable and multivariate logistic regression models were used for statistical analysis. Among the 280 eligible patients with UC with a median follow-up time of 14 (interquartile range, 10.0-18.0) years, those with a high MES were more likely to develop malignant transformation. High MES positively correlated with the degree of malignancy and was an independent risk factor for UC-associated dysplasia and colorectal cancer (CRC, odds ratio [OR], 9.223; 95% confidence interval [CI], 1.160-73.323; p = 0.036). Disease duration >5 years (OR, 2.05; 95% CI, 1.177-3.572; p = 0.011), immunomodulator use (OR, 4.314; 95% CI, 1.725-10.785; p = 0.002), biologics nonuse (OR, 3.901; 95%CI, 2.213-6.876; p < 0.001), and Hb <90 g/L (OR, 2.691; 95% CI, 1.251-5.785; p = 0.011) were contributing factors for high MES. High MES could be a novel predictor of malignant transformation in UC. Clinicians should optimize the use of biologics and immunomodulators early and should actively correct anemia to improve the MES and then reduce the incidence of UC-associated dysplasia and CRC.


Immunoreactive luteinizing hormone-releasing hormone in the seminal plasma and human semen parameters.
A luteinizing hormone-releasing hormone (LH-RH)-like substance has been detected in human seminal plasma by a radioimmunoassay (RIA) with a highly specific anti-LH-RH antiserum. The seminal samples--not only the plasma itself but also the sample extracted by an acid/alcohol method--showed satisfactory displacement curves in our RIA system. The relationship between fertility and the LH-RH values in the seminal plasma was studied by comparing the peptide levels with sperm concentration and motility. By these two parameters, 103 samples were divided into four groups. In the low-concentration groups (oligozoospermic patients), the hormonal concentrations differed significantly (P less than 0.05) between those specimens demonstrating good and poor motility. These data suggest that this immunoreactive LH-RH may play a role in human spermatogenesis.


Effect of Singing on Symptoms in Stable COPD: A Systematic Review and Meta-Analysis.
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease which feature is progressive airflow obstruction. Singing is a popular and convenient activity that requires people to manage their lung volumes and airflow actively. Despite the well-known benefits of singing to healthy people, the specific effect still remains unclear. To investigate the mental and psychological benefits of singing in patients with stable COPD. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA) on randomized controlled trials (RCTs) including singing exercise as the main intervention in stable COPD. We searched 8 electronic databases, including Web of Science, PubMed, Embase, Cochrane Library, Clinical Trials.gov, and the Physical Therapy Evidence Database (PEDro), CNKI, and Wanfang Database from inception until May 2022. The searching languages was English or Chinese. Data extraction using standardized templates was performed by two independent reviewers. The quality of the studies was assessed using the PEDro scale. Data synthesis was performed with Revman 5.4. The pooled effect sizes are reported by MD and 95% CI. Five RCTs involving 333 patients with stable COPD were included in this meta-analysis. Singing was regarded as the main intervention in the experimental group. Meta-analysis revealed that singing improves quality of life on Short Form 36 physical component summary (SF-36 PCS) (MD = 12.63, 95% CI: 5.52 to 19.73, P < 0.01) and respiratory muscle in maximal expiratory pressure (PEmax) (MD = 14.30, 95% CI: 0.87 to 27.73, P = 0.04) in patients with COPD. However, it has limited effects on Short Form 36 mental component summary (SF-36 MCS), lung function, exercise capability, and adverse mental state. Based on results of the meta-analysis, singing could be used to improve quality of life (SF-36 PCS) and respiratory muscles (PEmax) in patients with COPD.


Characteristics of Lumbar Bone Density in Middle-Aged and Elderly Subjects: A Correlation Study between T-Scores Determined by the DEXA Scan and Hounsfield Units from CT.
To describe the characteristics of lumbar bone density in middle-aged and elderly subjects and explore whether there is a correlation between computed tomography (CT) values and the bone mineral density (BMD) T-scores of the lumbar vertebral cancellous bone. Forty-two subjects, including 25 males and 17 females, with a mean age of 56 years, who underwent BMD measurement and lumbar multislice spiral CT scan at the China Rehabilitation Research Center from January 2019 to December 2019 were selected. Dual-energy X-ray absorptiometry (DEXA) was applied to obtain the total BMD T-scores of the lumbar L1-L4 vertebrae. The CT values decreased from L1 to L4 and were 145.91 ± 8.686 HU, 143.18 ± 8.598 HU, 137.39 ± 8.276 HU, and 135.23 ± 8.219 HU, respectively. The total CT value of L1-L4 was 140.43 ± 4.199 HU. The mean total BMD T-score of L1-L4 was -0.94. The CT values of the L1-L4 vertebrae were positively correlated with the total BMD T-scores of L1-L4 (r = 0.349, P < 0.001). The CT value of the left third of the same vertebrae was the highest, and there was a strong positive correlation between the regional CT value of the lumbar spine and the entire vertebra CT values (r > 0.7). The CT values of the lumbar spine can assist the measurement of the T-scores of lumbar BMD, which could aid in early opportunistic screening for osteopenia and preventing osteoporosis and vertebral compression fractures in middle-aged and elderly subjects. This trial is registered with ChiCTR2100049571.


8-phenyltheophylline: a potent P1-purinoceptor antagonist.
8-Phenyltheophylline was more potent than theophylline in antagonizing the inhibitory effects of adenosine in guinea-pig driven left atrium, rabbit basilar artery and electrically stimulated guinea-pig ileum preparations. In guinea-pig atrium and ileum, the antagonism of adenosine responses by the methylxanthines is of a competitive nature, but in rabbit basilar artery it does not appear to be so. In all three preparations, the effects of theophylline and 8-phenyltheophylline could be reversed by washing. It is concluded that 8-phenyltheophylline is a more potent P1-purinoceptor antagonist than theophylline.


Cytokine storm plays a direct role in the morbidity and mortality from influenza virus infection and is chemically treatable with a single sphingosine-1-phosphate agonist molecule.
Cytokine storm defines a dysregulation of and an excessively exaggerated immune response most often accompanying selected viral infections and several autoimmune diseases. Newly emerging and re-emerging infections of the respiratory tract, especially influenza, SARS, and hantavirus post considerable medical problems. Their morbidities and mortalities are often a direct result of cytokine storm. This chapter visits primarily influenza virus infection and resultant cytokine storm. It provides the compelling evidence that illuminates cytokine storm in influenza pathogenesis and the clear findings that cytokine storm is chemically tractable by therapy directed toward sphingosine-1-phosphate receptor (S1PR) modulation, specifically S1P1R agonist therapy. The mechanism(s) of how S1P1R signaling works and the pathways involved are subjects of this review.


Airway remodeling contributes to the progressive loss of lung function in asthma: an overview.
Airway inflammation, airflow obstruction, and bronchial hyperresponsiveness are characteristic phenotypic features of asthma. Clinically, airflow obstruction in asthma often is not fully reversible, and many asthmatic subjects experience an accelerated and progressive loss of lung function over time. Histopathologic studies of the asthmatic airway have demonstrated stereotypic changes that might explain the loss of lung function that many patients with asthma experience. The notion of airway remodeling in asthma postulates that the alteration of the structure and function of key airway constituents, including airway smooth muscle, epithelium, blood vessels, and mucus glands, might explain, at least in part, the progressive loss of lung function that is observed clinically. Inflammation driven by CD4(+) lymphocytes and mediated by effector cells, particularly the eosinophil, appears to modulate the function of mesenchymal cells, including fibroblasts and myofibroblasts, changing the composition of the airway wall matrix. Changes in the airway epithelium might alter the function of the underlying smooth muscle and the composition of the matrix and could drive inflammation. Alterations in the structure and function of airway smooth muscle change the mechanical properties of the airway wall and might also affect the function of other airway constituents. A variety of experimental models have identified candidate mechanisms and mediators for these observed changes, which are thus potential therapeutic targets. However, clinical studies to date have been disappointing, and it remains to be seen whether targeted therapies will prevent the progressive loss of lung function seen in asthma.


Cassava starch films containing acetylated starch nanoparticles as reinforcement: Physical and mechanical characterization.
This paper reports the use of acetylated starch nanoparticles (NPAac) as reinforcement in thermoplastic starch films. NPAac with an average size of approximately 500 nm were obtained by nanoprecipitation. Fourier transform infrared (FTIR) and thermogravimetric analysis (TGA) indicated that NPAac are more thermally stable and essentially amorphous when compared with acetylated starch. Thermoplastic starch films with different proportions of NPAac (0.5, 1.0, 1.5, 10.0%, w/w) were obtained and characterized by scanning electron microscopy (SEM), water vapor permeability (WVP), adsorption isotherms, TGA and mechanical tests. The inclusion of reinforcement caused changes in film properties: WVP was lowered by 41% for film with 1.5% (w/w) of NPAac and moisture adsorption by 33% for film with 10% (w/w) of NPAac; and the Young's modulus and thermal stability were increased by 162% and 15%, respectively, for film with 0.5% (w/w) of NPAac compared to the starch film without the addition of NPAac.


Chronic exposure to dexamethasone induces hypomethylation of ornithine decarboxylase genes in a human myeloma cell line.
Chronic exposure of a human myeloma cell line to dexamethasone resulted in a selection of cells resistant to the growth-inhibitory action of the glucocorticoid. Upon acute exposure of the parental myeloma cells to dexamethasone growth inhibition was associated with depression of ornithine decarboxylase (ODC, EC 184.108.40.206) activity. However, in cells adapted to grow in the presence of micromolar concentrations of dexamethasone, ODC activity was fully comparable to that in the parental cells. Restriction enzyme analyses with the two isoschizomers HpaII and MspI as well as with the methylation-sensitive CfoI, indicated that the otherwise heavily methylated ODC gene(s) were rendered hypomethylated in the myeloma cells resistant to dexamethasone. This hypomethylation within and/or around ODC genes was associated with a 2-4-fold enhancement of accumulation of ODC mRNA.


Investigation of Tumor Cell Behaviors on a Vascular Microenvironment-Mimicking Microfluidic Chip.
The extravasation of tumor cells is a key event in tumor metastasis. However, the mechanism underlying tumor cell extravasation remains unknown, mainly hindered by obstacles from the lack of complexity of biological tissues in conventional cell culture, and the costliness and ethical issues of in vivo experiments. Thus, a cheap, time and labor saving, and most of all, vascular microenvironment-mimicking research model is desirable. Herein, we report a microfluidic chip-based tumor extravasation research model which is capable of simultaneously simulating both mechanical and biochemical microenvironments of human vascular systems and analyzing their synergistic effects on the tumor extravasation. Under different mechanical conditions of the vascular system, the tumor cells (HeLa cells) had the highest viability and adhesion activity in the microenvironment of the capillary. The integrity of endothelial cells (ECs) monolayer was destroyed by tumor necrosis factor-α (TNF-α) in a hemodynamic background, which facilitated the tumor cell adhesion, this situation was recovered by the administration of platinum nanoparticles (Pt-NPs). This model bridges the gap between cell culture and animal experiments and is a promising platform for studying tumor behaviors in the vascular system.


Indanyloxyacetic acid-sensitive chloride channels from outer membranes of skeletal muscle.
In mature mammalian muscle, the chloride conductance of the membrane is an important factor in the regulation of excitability. Up to now, no ligand was available for the biochemical characterization of muscle chloride channels. In order to localize and characterize these channels, we have used indanyloxyacetic acid (IAA)-94, a ligand previously used for epithelial Cl- channels (Landry, D. W., Reitman, M., Cragoe, E. J., Jr., and Al-Awqati, Q. (1987) J. Gen. Physiol. 90, 779-798; Landry, D. W., Akabas, M. H., Redhead, C., Edelman, A., Cragoe, E. J., Jr., and Al-Awqati, Q. (1989) Science 244, 1469-1472). IAA induced myotonic responses when microinjected into mature mouse muscle fibers, indicating a blockade of Cl- channels from the cytoplasmic side. Membrane vesicles were prepared from rabbit skeletal muscle and separated by sucrose gradient centrifugation. Fractions obtained (in the order of increasing density) were sarcolemma (SL), T-tubules (TT), sarcoplasmatic reticulum (SR), and triads and mitochondria (TR/M). The fraction enriched for SL was characterized by high specific binding capacity for [3H]saxitoxin (Na+ channel), whereas TT-rich fractions bound [3H]PN 200-110 (dihydropyridine receptor) with high specific activity. Upon patch-clamping of lipid supplemented vesicles, IAA-sensitive Cl- channels were found in the SL fraction but not in the SR. Highest specific activities in electrical diffusion potential sensitive 36Cl transport and [3H]IAA-94 binding were found in the SL. SL vesicles were solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1- propanesulfonate and subjected to IAA-Sepharose affinity chromatography. Specifically bound protein was eluted with 100 microM IAA-94 and either analyzed by SDS-gel electrophoresis or reconstituted into phospholipid vesicles. The eluate contained four polypeptides (specifically bound, mapp 110-120 and 60 kDa; unspecifically bound mapp 67 and 50 kDa) and was highly enriched for IAA-sensitive chloride channels as shown by patch-clamping after reconstitution. The IAA-sensitive 100/280-picosiemens chloride channels of the sarcolemma are likely to be responsible for its major chloride conductance and thereby for the stabilization of resting potential.


Prespecialist perceptions of three-dimensional heart models in anatomical education.
This article aims to discuss the use of three-dimensional (3D) printed models of vascular variation cases as an educational tool for undergraduate and postgraduate anatomy students. This advanced study involved ten anatomy assistants who were provided with five distinct cases of congenital cardiovascular variations, each accompanied by a computed tomography angiography (CT-A) and 1:1 solid model format. The residents were asked to generate perceptions for both formats and then compare these perceptions based on identifying the variation, defining the structural features, and evaluating relevant educational perspectives. The vascular origin measurement values compared to the statistically evaluated real values of the related cases showed that models were 1:1 identical copies. Qualitative assessment feedback from five stations supported the usefulness of 3D models as educational tools for organ anatomy, simulation of variational structures, and overall medical education and anatomy training. Models showcasing different anatomical variations such as aortic arch with Type 2 pattern, a right-sided aortic arch with Type 2 pattern, an aberrant right subclavian artery, arteria lusoria in thorax, and a left coronary artery originating from pulmonary trunk in an Alcapa type pattern allow for better analysis due to their complex anatomies, thus optimizing the study of variation-specific anatomy. The perception level in the 3D model contained higher points in all of the nine parameters, namely identification of cardiovascular variations, defining the vessel with anomaly, aortic arch branch count and appearance order, feasibility of using it in peers and student education. 3D models received a score 9.1 points, while CT-A images were rated at 4.8 out of 10. 3D printed anatomical models of variational cardiovascular anatomy serve as essential components of anatomy training and postgraduate clinical perception by granting demonstrative feedback and a superior comprehension of the visuospatial relationship between the anatomical structures.