Augmented estimation for t-year survival with censored regression models.
Reliable and accurate risk prediction is fundamental for successful management of clinical conditions. Estimating comprehensive risk prediction models precisely, however, is a difficult task, especially when the outcome of interest is time to a rare event and the number of candidate predictors, p, is not very small. Another challenge in developing accurate risk models arises from potential model misspecification. Time-specific generalized linear models estimated with inverse censoring probability weighting are robust to model misspecification, but may be inefficient in the rare event setting. To improve the efficiency of such robust estimation procedures, various augmentation methods have been proposed in the literature. These procedures can also leverage auxiliary variables such as intermediate outcomes that are predictive of event risk. However, most existing methods do not perform well in the rare event setting, especially when p is not small. In this article, we propose a two-step, imputation-based augmentation procedure that can improve estimation efficiency and that is robust to model misspecification. We also develop regularized augmentation procedures for settings where p is not small, along with procedures to improve the estimation of individualized treatment effect in risk reduction. Numerical studies suggest that our proposed methods substantially outperform existing methods in efficiency gains. The proposed methods are applied to an AIDS clinical trial for treating HIV-infected patients.


Autocrine angiogenic vascular prosthesis with bone marrow transplantation.
Synthetic vascular prostheses are foreign bodies, so that blood coagulation can occur on their luminal surfaces, causing graft occlusion very frequently in prostheses of small diameter. A vascular prosthesis needs angiogenesis for endothelialization of the luminal surface, as endothelial cells have natural and permanent antithrombogenic properties. To induce capillary growth into the graft, we developed a method of transplanting bone marrow cells, which are primitive, strong enough to survive, and create blood cells, resulting in the inducement of capillary growth. In an animal experiment, marrow cells were infiltrated into the walls of long-fibril expanded polytetrafluoroethylene (ePTFE) vascular grafts. The grafts were implanted in the abdominal aortic position of 24 dogs autologously. Marrow cells survived and continued exogenous hemopoiesis for up to six months and were immunohistochemically reactive to basic fibroblast growth factor (bFGF). All the grafts older than three weeks had complete endothelialization and maintained their patency. Twenty grafts without bone marrow were implanted as controls. Endothelialization was present at anastomotic sites, but other areas were covered with fresh thrombi. Four out of seven control grafts were patent with endothelial cell lining at six months, but three were occluded and one of the four grafts was still covered with a thrombus layer. Bone marrow with its unique native properties produced autocrine angiogenicity in the graft.


Sensitive and convenient high-performance liquid chromatographic method for the determination of mitomycin C in human plasma.
An improved high-performance liquid chromatographic assay for the cytostatic drug mitomycin C in plasma is presented. The principal steps are precipitation of plasma proteins with acetonitrile, lyophilization of the supernatant and reversed-phase chromatography on a Hypersil ODS 5 microm column with 0.01 M NaH2PO4 buffer (pH 6.5)-methanol (70:30, v/v) in isocratic mode. At a flow-rate of 1.3 ml/min a column pressure of 180-220 bar resulted. Porfiromycin served as internal standard. UV detection was performed at 365 nm. Quantitation limit based on a coefficient of variation <10% in intra- and inter-day assay was 5 microg/l mitomycin C, detection limit based on a signal-to-noise ratio of 3 was 1 microg/l. Recovery was 100% and linearity was shown for the whole range of concentration (1-500 microg/l). None of the five drugs used during chemoembolisation interfered with the assay in vitro. The assay meets the requirements for pharmacokinetic studies of mitomycin C in patients as regards sensitivity and ease of use.


The roles of preB cell receptor in early B cell development and its signal transduction.
The preB cell receptor is expressed for a short period after mu heavy chain is produced, that is, at the large preB cell stage in B cell development. The severe impairment of B cell differentiation observed in mice deficient for the preB cell receptor clearly demonstrated the importance of the preB cell receptor in B cell development. Analyses of bone marrow precursor B cells in normal and B cell-deficient mutant mice indicated the preB cell receptor transduced signals to drive cell cycle and to induce allelic exclusion. The proliferation of the preB cell receptor-expressing cells leads to the selective expansion of cells which have succeeded in the productive rearrangement of mu heavy chain gene. This process builds up a preB cell pool large enough to generate sufficient numbers of mature B cells. The preB cell receptor appears to induce allelic exclusion by shutting off the expression of recombinase activation gene (RAG). In order to analyse the signal transduction pathway downstream of the preB cell receptor, we have developed a new system in which cross-linking of Ig beta expressed on bone marrow proB cells mimics the signalling through the preB cell receptor to induce differentiation from proB to small preB cells.


Early detection of premalignant lesions and oral cancer.
Cancers of the oral cavity account for approximately 3% of malignancies diagnosed annually in the United States. As with other upper aerodigestive tract cancers, 5-year survival rates for oral cavity cancers decrease with delayed diagnosis. Cancers of the oral cavity are thought to progress from premalignant/precancerous lesions, beginning as hyperplastic tissue and developing into invasive squamous cell carcinoma. Despite the general accessibility of the oral cavity during physical examination, many malignancies are not diagnosed until late stages of disease. To prevent malignant transformation of these oral precursor lesions, multiple screening and detection techniques have been developed to address this problem.


Ultrastructural changes in hatching-gland cells of pike embryos (Esox lucius L.) and evidence for their degeneration by apoptosis.
Around hatching, when the pike embryo sheds its acellular egg envelope, marked changes occur in the cellular covering of the embryo. This cellular covering consists of a peridermal layer and a monolayered presumptive epidermis. The periderm begins to disintegrate shortly before hatching and is sloughed off in the first posthatching period. The cellular covering produces hatching enzyme, the protease that partly dissolves the zona radiata interna of the acellular envelope. By means of the peroxidase-anti-peroxidase staining method with antibodies against hatching enzyme the cells producing this enzyme (hatching gland cells, HGCs) could be identified ultrastructurally. They are interspersed as single cells between the periderm and the presumptive epidermis. The secretory cycle of the HGC was studied. Hatching enzyme is released by an exocytotic secretory process in which multiple secretion into a "secretion vacuole" predominates. Exocytosis into surrounding intercellular spaces also occurs. These results show that the HGCs are merocrine glands. The HGC also has some "holocrine nature," however, in that only a single, massive release of its secretory product occurs. The death of the transitory HGCs in posthatching stages is characterized by condensation of the cell, formation of surface protuberances and splitting up into globular cell fragments. Eventually these fragments are ingested by epidermal cells and digested. These results lead to the conclusion that the pike HGCs degenerate by apoptosis, unlike true holocrine cells.


[The history of sterility in Antiquity. III. The anatomy and physiology of conception in the work of Soranos of Ephesus].
Soranos was highly regarded as the first and the most famous gynecologist in the antiquity. In point of fact, Soranos was not really a gynecologist but, he was the first to write a treatise about "gynecology". This work came down to us incomplete. In this study we analyse the conception's theories of Soranos.


Validation of the Chinese version of the COVID-19 Phobia Scale among Chinese college students.
Different languages and versions of the COVID-19 Phobia Scale (C19P-S) have been developed and tested in several countries. Chinese college students are a large vulnerable group and are susceptible to psychological problems during the COVID-19 pandemic. However, no studies had yet examined the reliability and validity of the C19P-S in China among college students group. This study aims to evaluate the COVID-19-related phobia of Chinese college students and examine the reliability and validity of this scale. A total of 1689 Chinese college students participated in this study from April 27 to May 7, 2022. They finished the online questionnaire including demographic information and C19P-S. Cronbach's alpha and split-half reliability were used to examine the internal consistency of the scale. Confirmatory factor analysis was further used to examine the scale's construct validity. Convergence validity was also confirmed. This scale in Chinese had high reliability and validity. The Cronbach's alpha and split-half reliability of the total scale were 0.960 and 0.935, respectively. The construct validity-related indicators of the total scale met the standards (RMSEA = 0.064, IFI = 0.907, TLI = 0.906, and CFI = 0.907). Regarding the subscales, the composite reliability (CR) and average variance extracted (AVE) also met the cutoff values (CR > 0.7 and AVE >0.5). Comparison between gender groups showed that total and subscale scores between male and female students differed significantly. The Chinese version of the C19P-S was appropriate for evaluating phobic symptoms among Chinese college students. Therefore, this tool could be used to evaluate the mental health of college students in the future.


IQGAP2 acts as an independent prognostic factor and is related to immunosuppression in DLBCL.
Almost one-third of patients with diffuse large B-cell lymphoma (DLBCL) cannot be cured with initial therapy and will eventually succumb to the disease. Further elaboration of prognostic markers of DLBCL will provide therapeutic targets. IQ motif-containing GTPase activating protein 2 (IQGAP2) acts as a tumour suppressor in hepatocellular, prostate, and gastric cancers. However, the role of IQGAP2 in DLBCL remains unclear. We collected mRNA expression data from 614 samples and the corresponding clinical information. The survival time of patients was compared between groups according to the mRNA expression level of IQGAP2. Survival analyses were performed in different subgroups when considering the effect of age, tumour stage, serum lactate dehydrogenase (LDH) concentration, performance status, and the number of extra nodal disease sites. The biological processes associated with IQGAP2-associated mRNAs were analysed to predict the function of IQGAP2. The correlation of IQGAP2 mRNA with immunosuppressive genes and leukocyte infiltration were analysed. The overall survival of patients with increased IQGAP2 mRNA levels was reduced even after aggressive treatment independent of age, tumour stage, serum LDH concentration, performance status, and the number of extra nodal disease sites. Furthermore, the biological processes of IQGAP2-associated mRNAs were mainly immune processes. IQGAP2 mRNA expression was correlated with the expression of immunosuppressive genes and leukocyte infiltration. IQGAP2 mRNA is an independent prognostic factor and is related to immunosuppression in DLBCL. This discovery may provide a promising target for further development of therapy.


EEG frontal lobe asymmetry as a function of sex, depression severity, and depression subtype.
To investigate possible contributors to the inconsistent association between frontal lobe asymmetry (FLA) and depression, EEG data were collected across five frontal sites, and examined for their associations with four subtypes of depression (Depressed mood, Anhedonia, Cognitive depression, Somatic depression). One hundred community volunteers (54 males, 46 females) aged at least 18 yr completed standardized scales for depression and anxiety, and gave EEG data under Eyes Open and Eyes Closed conditions. Results indicated that, although there was no significant correlation between the differences in EEG power across each of the five pairs of frontal sites and total depression scores, there were several meaningful correlations (accounting for at least 10% of the variance) between specific EEG site differences data and each of the four depression subtypes. There were also different patterns of association between FLA and the depression subtypes according to sex, and total depression severity. These findings help to explain the apparent inconsistency in previous FLA-depression results, and argue for a more nuanced approach to this hypothesis.


Effects of endothelin ETA receptor antagonism with PD 156707 on hemodynamics and renal vascular resistance in rabbits.
The objective of this study was to determine the in vivo effectiveness of the selective endothelin ETA receptor antagonist PD 156707 (sodium 2-benzo[1,3]dioxol-5-yl-4-(4-methoxy-phenyl)-4-oxo-3-(3,4,5-trimet hoxy- benzyl)-but-2-enoate). Effectiveness was defined by the ability of the compound to block increases in renal vascular resistance and mean arterial blood pressure induced by an intravenous bolus of 0.3 nmol/kg of human endothelin-1 in pentobarbital anesthetized rabbits. Different groups of rabbits received hour long intravenous infusions of PD 156707 at doses of 0.003, 0.01, 0.03 or 0.3 mg/kg per h. During baseline conditions, mean arterial blood pressure, heart rate, renal blood flow, and renal vascular resistance were similar among the groups. The intravenous bolus of endothelin-1 significantly decreased mean arterial blood pressure (82 +/- 3 mmHg to 65 +/- 3 mmHg, P < 0.05) and increased renal vascular resistance (2.8 +/- 0.3 mmHg/ml per min to 9.2 +/- 1.1 mmHg/ml per min, P < 0.05) in untreated control animals. At doses of 0.3 and 0.03 mg/kg per h, PD 156707 virtually abolished endothelin-1 induced increases in renal vascular resistance, but did not affect the endothelin-1 induced decrease in mean arterial blood pressure. At 0.01 and 0.003 mg/kg per h, PD 156707 also inhibited endothelin-1 induced increases in renal vascular resistance but the effects were less striking, leading to the conclusion that the minimum effective intravenous dose of the compound in rabbits is in the range of 0.01-0.03 mg/kg per h. The results of this study demonstrate that PD 156707 is an extremely potent and highly selective endothelin ETA receptor antagonist. In addition, this study demonstrates the utility of renal vascular resistance as an in vivo bioassay for evaluating the selective vascular effects of endothelin receptor antagonists in this species.


Faraday waves on a nematic liquid crystal, and its coupling with Marangoni convection about the thermal phase transition.
Using a linear hydrodynamic theory, we demonstrate that Faraday waves occur in liquid crystalline fluids. The use of already experimentally known material parameters of a N-(4-methoxybenzylidene)-4-butylaniline liquid crystal allows us to confirm and realize the predictions of this theory. It provides the critical wave number and necessary driving acceleration at instability wave onset. Additionally, these observables experience an abrupt change originated by Marangoni convection due to the temperature gradient at the isotropic-nematic phase transition temperature. Correspondingly, the Marangoni number versus temperature also shows a sharp change in the transition temperature.


Orbital lymphoma mimicking optic nerve meningioma.
To describe two patients with orbital lymphoma mimicking optic nerve meningioma. Retrospective case review. Both patients presented in their sixth decade with gradually increasing proptosis and decreasing vision. Computerized tomography revealed homogeneous masses encasing the optic nerves, which in conjunction with the clinical presentations were felt to represent optic nerve meningiomas. Biopsy, however, led to a diagnosis of lymphoma of mucosal-associated lymphoid tissue origin in one and a well-differentiated non-Hodgkin's lymphoma in the other. Orbital lymphoma surrounding the optic nerve may mimic the clinical and radiological appearance of an optic nerve meningioma.


An in vitro chemosensitivity test for the screening of anti-cancer drugs in childhood leukemia.
We applied the MTT dye reduction assay to the anti-cancer drug sensitivity test using short-term microplate cultures. Blast cells were cultured with approximately 25 anti-cancer drugs for 4 days. After cultivation, MTT dye was placed in each well, and the formazans generated by living cells were dissolved in acidified isopropyl alcohol. The absorbance of each well was measured at a scanning microplate photometer. When we made the table of the cytotoxicity index (CI) that was classified into anti-cancer drugs and concentrations for each leukemic sample, it was possible to compare efficacy with different drugs and to select the effective ones. Retrospectively, the in vitro results were compared with the clinical responses of the 34 patients (26 of acute lymphocytic leukemia [ALL] and eight of acute nonlymphoblastic leukemia [ANLL]) who were treated by combination chemotherapy. The following results were obtained: true-positive rate, 78.1%; true-negative rate, 57.1%; and predictive accuracy, 74.4%. Therefore, the MTT assay-CI table might serve as a reliable tool for the selection of effective chemotherapy in patients with acute leukemia.


Sampling or intermittency in hand control system dynamics.
A hand control model is proposed. Investigation of the hand's intermittency synchronization shows it corresponds to an input-synchronized sampler rather than the clock-synchronized sampler more typical of engineering systems. A velocity control mechanism, similar to that in an eye tracking system is shown to be absent in the hand. A quantitative transfer function for predictable inputs serves further to define the hand's input adaptive characteristics. Stability margin adjustments of a linear reduced model enabled us to match the available quantitative data. The most exciting result of this study is the evidence for intermittency: a refractory period shown in the short pulse experiment, peaks in the frequency response experiments, and a saccadic sequence of steps in response to an open loop step input and to a closed loop ramp input.


Vibrational spectra study of fluorescent dendrimers built from the cyclotriphosphazene core with terminal dansyl and carbamate groups.
The FTIR and FT Raman spectra of the "Janus"-type dendrimers, possessing five carbamate groups on one side and five fluorescent dansyl derivatives on the other side, with amide G(1) and hydrazone G(2) central linkages were studied. These surface-block dendrimers are obtained by the coupling of two different dendrons. The FTIR and FT-Raman spectra of the zero generation dendrons, built from the hexafunctional cyclotriphosphazene core, with five dansyl terminal groups and one carbamate G(0v) and one oxybenzaldehyde function G(0v)' have been recorded. The structural optimization and normal mode analysis were performed for dendron G(0v)' on the basis of the density functional theory (DFT). The calculated geometrical parameters and harmonic vibrational frequencies are predicted in a good agreement with the experimental data. It was found that dendron molecule G(0v)' has a concave lens structure with planar -O-C(6)H(4)-CHO fragments and slightly non-planar cyclotriphosphazene core. The experimental IR and Raman spectra of dendron G(0v)' were interpreted by means of potential energy distributions. Relying on DFT calculations a complete vibrational assignment is proposed. The strong band 1597 cm(-1) show marked changes of the optical density in dependence of substituents in the aromatic ring. The frequencies of ν(N-H) bands in the IR spectra reveal the presence of the different types of H-bonds in the dendrimers.


Differentiating between reflex and spontaneous blinks using simultaneous recording of the orbicularis oculi electromyogram and the electro-oculogram in startle research.
The present study documents the differences between reflex and spontaneous blinks by recording the vertical electro-oculogram (EOG) along with the orbicularis oculi electromyogram (OO-EMG). EOG and OO-EMG were applied without fixation of the head in 15 freely moving children during an auditory startle experiment. Results revealed that the easily-recorded EOG shows the same relationships between orbicularis oculi contraction and velocity of lid movement in startle blinks as the head-constraining methods, e.g. the magnetic search coil, used in previous studies. The OO-EMG onset occurred before the EOG onset in most reflex blinks while no such pattern occurred for spontaneous blinks. In comparison with spontaneous blinks, reflex blinks showed a shorter duration between onset and peak and between onset and offset in OO-EMG and EOG. In addition, reflex blinks showed greater OO-EMG activity and smaller EOG-recorded lid movements compared with spontaneous blinks. Simultaneous recording of OO-EMG and EOG can distinguish reflex from spontaneous blinks and lid saccades in populations, e.g. children, that cannot tolerate head restraint and in experiments permitting or requiring movement.


Genetic analysis of patients with primary congenital glaucoma.
To determine the common gene mutation in patients with primary congenital glaucoma (PCG) in the Southeast region of Turkey via genetic analysis and to evaluate whether there were other gene mutations in these patients. A total of 25 patients with PCG were included in this study. We performed sequence analysis including all exons of cytochrome p450 1B1 (CYP1B1), myocilin (MYOC), forkhead box C1 (FOXC1), and paired-like homeodomain 2 (PITX2) genes of the obtained samples. Further, we analyzed the results using the Nextgen analysis program. The CYP1B1 gene mutation was detected in 20 (80%) of 25 patients, and FOXC1 gene mutation was detected in one (4%) patient. The mutation site of nine (45%) of the 20 CYP1B1 genes was found in the second exon. The pathogenic variant (p.Gly61Glu) was observed in 12 (60%) patients (in the first and second exons); the mutation type of six (50%) of these patients was homozygous. The mutation site of one patient with FOXC1 gene mutation was found to be in the first exon; its pathogenic variant was p.Met400lle. The mutation type in this gene was observed to be heterozygous. Lastly, there were no mutations in the MYOC, FOXC1, and PITX2 genes in combination with the CYP1B1 gene mutation. The most common cause of PCG in our region is the CYP1B1 gene mutation, and the most frequent pathogenic variant is c.182G > A (p.Gly61Glu). We also determined that the CYP1B1 gene mutation was alone and did not occur with other gene mutations (MYOC, FOXC1, and PITX2).


Phytochemical analysis of Daphne pontica L. stems with their pro-apoptotic properties against DU-145 and LNCaP prostate cancer cells.
Daphne pontica is an endemic plant grown wild in the North part of Iran, with anticancer activities. This study aims to analyze the phytochemistry and screen the cytotoxic activity of new bioactive compounds against a panel of cancer cells, in addition to proapototic properties against prostate cancer cells. Purification procedure was done using repeated column chromatographies by MPLC and HPLC systems. The structures were elucidated by the NMR and exact mass spectroscopy, stereochemistry by NOESY, and absolute configuration by electronic circular dichroism (ECD) spectra. Cytotoxicity was done against DU 145, LNCaP, HeLa, MCF-7, and MDA-MB 231 cells by standard MTT assay. An annexin V/PI assay was performed to measure the type of death following treatment with these compounds for 48 h, followed by the caspase-3 activity test. In this study, one new dilignan named lignopontin A (9), in addition to 13 known compounds including two phenolic acids (3, 5), one flavanone (6), one bis flavonoid (1), one cumarin glycoside (2), one mono (4) and two dicumarins (10, 11), two lignans (7, 8), and three daphnane diterpenoids (12-14) were isolated for the first time from D. pontica stems. Complete spectral data of compound 12, named as 6,7α-epoxy-5β-hydroxy-9,13,14-ortho-(4,2E)-pentadeca-2,4-diene-1-yl)-resiniferonol, and compound 14, named as 6,7α-epoxy-5β-hydroxy-9,3,14-ortho-(2,4E)-pentadeca-2,4-di-1-yl)-resiniferonol-12β-yl-acetate are reported for the first time. In the MTT assay of newly described compounds against a panel of cancer cells, compounds 9, 12, and 14 possessed moderate to potent cytotoxicity against prostate, breast, and cervical cancer cells in a dose-dependent manner. Flow cytometry analysis against prostate cancer cells indicated that the cytotoxicity of compounds 12 and 14 was due to their ability to induce apoptosis. In the case of compound 9, in Du 145 cells, cell death was mainly through apoptosis. In contrast, LNCaP cells showed both apoptosis and necrotic cell death, predominated by necrosis at the higher concentrations. Caspase-3 activity confirmed apoptosis observed in these compounds through the caspase pathway in prostate cancer cells. D. pontica is a new source of dimeric phenolic compounds, including bisflavonoids, phenylpropanoid-cumarin adduct, and dilignans, as well as daphnane diterpenoids with resiniferonol core with long-chain orthoester moieties. In cytotoxicity screening, compounds 9, 12, and 14 inhibited the growth of DU-145 and LNCaP cells in a dose-dependent manner with IC50 varied from 0.9 - 27.3 and 25.2 - 87.4 μM, respectively. Among them, 9 exhibited selective growth inhibition against DU 145 treated cells. LNCaP cells demonstrated the highest sensitivity to treatment with compound 12.


Combinations of self-reported rhinitis, conjunctivitis, and asthma predicts IgE sensitization in more than 25,000 Danes.
Allergic rhinitis (AR), allergic conjunctivitis (AC), and asthma composing multiple phenotypes and improved understanding of these phenotypes and their respective risk factors are needed. The objective of this study was to define the prevalence of AR, AC, and asthma and their association with allergen-specific immunoglobulin E (sIgE) sensitization in a large cohort of blood donors and identify risk factors. From the nationwide population-based Danish Blood Donor Study, 52,976 participants completed an electronic questionnaire including AR, AC, asthma, allergic predisposition, and childhood residence. Of these, 25,257 were additionally tested for sIgE to inhalation allergens (Phadiatop). The prevalence of sIgE sensitization, AR, AC, and asthma was 30%, 19%, 15%, and 9%, respectively. The youngest birth cohorts had the highest prevalence of sIgE sensitization and symptoms of asthma, AR, and AC, and for asthma, they apparently experienced symptoms at an earlier age. The sIgE sensitization was positively associated with male sex. The sIgE seroprevalence was higher in participants with both AR and AC (ARC) than in participants with either AR or AC. Allergic predisposition and sIgE sensitization increased the risk of the diseases, while farm upbringing was associated with reduced prevalence of ARC, however, only in sIgE sensitized participants. Birth year, childhood residence, sIgE sensitization, and allergic predisposition were associated with asthma, AR, and AC prevalence. Individuals with self-reported ARC represent a primarily sIgE-positive phenotype, while those with either AR or AC represent more diverse phenotypes.


Transcranial brain atlas for school-aged children and adolescents.
Both fNIRS optodes and TMS coils are placed on the scalp, while the targeted brain activities are inside the brain. An accurate cranio-cortical correspondence is crucial to the precise localization of the cortical area under imaging or stimulation (i.e. transcranial locating), as well as guiding the placement of optodes/coils (i.e. transcranial targeting). However, the existing normative cranio-cortical correspondence data used as transcranial references are predominantly derived from the adult population, and whether and how correspondence changes during childhood and adolescence is currently unclear. This study aimed to build the age-specific cranio-cortical correspondences for school-aged children and adolescents and investigate its differences to adults. Age-specific transcranial brain atlases (TBAs) were built with age groups: 6-8, 8-10, 10-12, 12-14, 14-16, and 16-18 years. We compared the performance in both transcranial locating and targeting when using the age-appropriate TBA versus the adult TBA (derived from adult population) for children. These atlases provide age-specific probabilistic cranio-cortical correspondence at a high resolution (average scalp spacing of 2.8 mm). Significant differences in cranio-cortical correspondence between children/adolescents and adults were found: the younger the child, the greater the differences. For children (aged 6-12 years), locating and targeting errors when using the adult TBA reached 10 mm or more in the bilateral temporal lobe and frontal lobe. In contrast, the age-matched TBA reduced these errors to 4-5 mm, an approximately 50% reduction in error. Our work provides an accurate and effective anatomical reference for studies in children and adolescents.


The excimer laser: gross, light microscopic and ultrastructural analysis of potential advantages for use in laser therapy of cardiovascular disease.
Excimer lasers are pulsed gas lasers that use a mixture of a rare gas and halogen as the active medium to generate pulses of short wavelength, high energy ultraviolet light. A krypton-fluoride gas mixture was used to achieve an excimer emission at a wavelength of 248 nm. A total of 30 atherosclerotic coronary artery segments were irradiated over a range of pulse energies (250 to 750 mJ), repetition rates (2 to 25 Hz), average powers (1.9 to 18.8 watts) and cumulative exposures (3 to 12 seconds). In no case was there gross, light microscopic or ultrastructural evidence of the pathologic injury typically associated with continuous wave laser irradiation of coronary artery segments. Similar results were achieved after excimer laser irradiation of 30 samples of myocardium. Excimer irradiation of calcified aortic valve leaflets accomplished focal debridement without pathologic tissue injury; when total debridement was attempted, however, gross charring was observed. The paucity of pathologic alterations observed after excimer irradiation of cardiovascular tissue may prove beneficial in precisely controlling laser ablation of pathologic tissue without injury to the surrounding normal tissue. Clinical application of excimer laser irradiation requires resolution of several issues, including the development of suitable fiber optics and laser coupling, evaluation of potential ultraviolet toxicity, and demonstration that ultraviolet light can be transmitted through a blood-filled system.


Effects of continuous positive airway pressure therapy on left ventricular performance in patients with severe obstructive sleep apnea.
We investigated myocardial performance concerning obstructive sleep apnea (OSA) severity and the benefits of continuous positive airway pressure (CPAP) therapy. In this randomized sham-controlled trial, 52 patients (mean age, 49 years; 92%, males; mean AHI, 59) with severe OSA were randomly assigned to receive either CPAP or sham treatment for 3 months. The severity of OSA was determined using the apnea/hypopnea index (AHI), oxygen desaturation index (ODI), percentage of sleep time below 90% oxygen saturation (T90), and average O2 saturation during sleep (mean SpO2). We compared the changes in myocardial work after 3 months of CPAP (n = 26) versus the sham group (n = 26) at rest and during an exercise stress test. Unlike AHI or ODI, indices of hypoxemia including T90 and mean SpO2 were significantly correlated with global constructive work, as defined by work of left ventricle (LV) that contributes to LV ejection during systole (T90, β = 0.393, p = 0.012; mean SpO2, β = 0.331, p = 0.048), and global wasted work (GWW), as defined by work of LV that does not contribute to LV ejection (T90, β = 0.363, p = 0.015; mean SpO2, β = - 0.370, p = 0.019). After 3 months, GWW decreased (80.0 ± 49.2 to 60.8 ± 26.3, p = 0.009) and global work efficiency increased (94.0 ± 4.5 to 95.7 ± 2.0, p = 0.008) in the CPAP group compared to those in the sham group. At the 3-month follow-up exercise stress echocardiography, worsening of GWW during exercise was significantly decreased in the CPAP group compared to that in the sham group (p = 0.045 at 50 W). Hypoxemia indices were closely associated with myocardial performance in patients with severe OSA. CPAP treatment for 3 months improved left ventricular myocardial performance by decreasing wasted work and increasing work efficacy compared to the sham treatment.


The impact of advanced age-related macular degeneration on the National Eye Institute's Visual Function Questionnaire-25.
To assess visual function among patients diagnosed with age-related macular degeneration (AMD) by stage of disease and laterality. This is a cross-sectional cohort study of 739 AMD patients and their responses to the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) at time of study enrolment. Patients with AMD were categorized into Early/Intermediate AMD and three groups of advanced AMD: (i) neovascular AMD (NV), (ii) geographic atrophy (GA) and (iii) Both Advanced forms. These three advanced stages were further stratified into unilateral or bilateral advanced disease. Mean composite scores and subscale scores for 12 different areas were based on a 100-point scale with the lowest and highest possible scores set at 0 and 100, respectively. Scores for the advanced AMD groups were compared with Early/Intermediate AMD using general linear modelling. A total of 739 AMD patients (294 Early/Intermediate, 115 GA, 168 NVAMD and 162 Both Advanced) were included in the analysis. Mean composite scores were highest among Early/Intermediate patients (89.9), followed by patients diagnosed with unilateral disease in the Both Advanced (88.0) and NV (86.1) groups. Mean composite scores were similar for bilateral NV (82.9) and unilateral GA (81.7), and mean scores were lowest for the bilateral GA (71.3) and bilateral Both Advanced (68.5) groups. In general, this pattern persisted across the twelve subscales as well. Subscale scores ranged from a low of 35.1 for driving among bilateral Both Advanced patients to a high of 99.2 for colour vision among patients with unilateral Both Advanced. Overall, patients with unilateral advanced disease consistently had higher mean scores than their bilateral counterparts. The largest difference was 19.5 composite score points between the unilateral and bilateral Both Advanced groups, there was a difference of 10.4 points between the GA groups, and a relatively small difference of 3.2 points between the NV groups. We found large differences in visual function as reported from the VFQ-25 across the different types of advanced stage AMD groups and number of eyes affected with advanced AMD. These findings demonstrate the importance of accounting for the type and number of eyes affected by advanced stage AMD.


X-ray irradiation accelerates senescence in hippocampal neural stem/progenitor cells via caspase-1 activation.
Despite the effectiveness in controlling the progression of brain tumors, cranial irradiation often causes neuropsychological deficits in cancer survivors. Inflammation is considered a major cause of tissue injury from irradiation. The caspase-1 activation complexes (inflammasomes) can facilitate caspase-1 and IL-1β processing, which amplifies the inflammatory response. In the present study we examined whether caspase-1 activation contributes to irradiation-induced damage to neural stem and progenitor cells (NSPCs). We found that X-ray irradiation induced activation of caspase-1 in NSPCs in vitro and in vivo. Next, using a caspase-1 inhibitor (Ac-YVAD-CMK) to block caspase-1 activation in vitro and in vivo, we further demonstrated that X-ray irradiation may inhibit proliferation, induce senescence of NSPCs through caspase-1 activation. Together, our results suggest that caspase-1 activation is involved in irradiation-induced damage to NSPCs.


Kidney mitochondrial respiration in protein- and energy-malnourished rats.
Several lines of evidence show a close association between plasma membrane Na,K-ATPase and mitochondrial respiration. Extending the observation in human erythrocyte membrane (6), Na,K-ATPase activity has been shown to be elevated in kidney microsomal preparations from protein- and energy-malnourished rats (10). Kidney mitochondrial respiration was studied in these rats under various conditions of assay. Sucrose was used as a modifier of mitochondrial morphology and volume to study its effect on these mitochondria. Mitochondrial state 3 respiration was increased by 35% in protein-deficient rats (P less than 0.02). Vmax(ADP) of state 3 respiration was increased by about 47% in protein- as well as energy-restricted rats. Mitochondria from protein- and energy-deficient rats were more tightly coupled as compared to those from control group. Km apparent for (ADP) and (Pi) were elevated in protein- and energy-malnourished rats. The magnitude of increase was much more in energy-deficient rats. Morphological differences between the mitochondria from two dietary manipulations were reflected in differences in the responses of state 3 respiration, Km(ADP), state 4 respiration, and respiratory control ratios to changing sucrose concentrations. This increase in mitochondrial respiration parallels the increased Na,K-ATPase activity in these rats. Increased Km (ADP and Pi) for mitochondrial respiration are perhaps in response to increased availability of these metabolites in the cytosol. The sucrose effect, in addition, distinguishes the morphological differences in mitochondrial membrane due to protein or energy deficiencies. In conclusion, these results, to a great extent, support an association between the activity of Na,K-ATPase and mitochondrial respiration. The study of mechanism(s) which could contribute to the enhancement of mitochondrial respiration will be of general importance to the understanding of regulation of mitochondrial oxidative phosphorylation, and is of particular interest to us.


Boron isotopes in boninites document rapid changes in slab inputs during subduction initiation.
How subduction-related magmatism starts at convergent plate margins is still poorly understood. Here we show that boron isotope variations in early-formed boninites from the Izu-Bonin arc, combined with radiogenic isotopes and elemental ratios document rapid (~0.5 to 1 Myr) changes in the sources and makeup of slab inputs as subduction begins. Heterogeneous hornblende-granulite facies melts from ocean crust gabbros ± basalts fluxed early melting to generate low silica boninites. Hydrous fluids from slab sediments and basalts later fluxed the low silica boninites mantle source to produce high silica boninites. Our results suggest that initially the uppermost parts of the slab were accreted near the nascent trench, perhaps related to early low-angle subduction. The rapid changes in slab inputs recorded in the boninites entail a steepening subduction angle and cooling of the plate interface, allowing for subduction of slab sediment and basalt, and generating hydrous fluids at lower slab temperatures.


Solid state NMR study of sodium thiocyanate/poly(ethylene oxide) electrolytes.
1H-, 13C-, 23Na-solid state NMR measurements have been used to characterise the morphology and the dynamics of several NaSCN-PEO mixtures. Selective 13C-MAS experiments allowed to determine the composition of the (PEO)nNaSCN samples in terms of the different phases present, as well as the real stoichiometry of the crystalline complex. 1H- and 13C-spin-lattice relaxation times provided estimates of the dimensions of the different domains and gave information on the dynamics of the polymer chains. 23Na-MAS spectra and 2D nutation experiments allowed to individuate the presence of different environments for the sodium cations on the basis of their quadrupolar interactions.


Comparative analysis of the clinical characteristics and outcomes of patients with Wilms tumor in the United Kingdom and Japan.
Wilms tumor (WT) demonstrates epidemiological differences by world region and ethnicity. To enhance understanding of these differences, we retrospectively analyzed clinical trial data sets from the UK and Japan over a 20-year period. We used data from three consecutive clinical trials in the UK and a single study in Japan that enrolled patients diagnosed during 1996-2015, to compare clinical characteristics and outcomes between countries. During 1996-2015, 1395 patients in the UK and 537 in Japan were included. Japanese patients have a significantly younger median age at diagnosis than those in the UK (28 months vs 39 months). The proportion of patients with stage IV, large tumors, and anaplastic histology appears to be higher in the UK than in Japan (18% vs 11%, 62% vs 49%, 8% vs 3%, respectively). During 2005-2015, 77 hospitals treated WT in Japan compared with only 20 hospitals in the UK. Five-year overall survival of patients with WT was over 90% in both countries, but five-year event-free survival of patients with stage IV was significantly lower in Japan than in the UK (50.0% vs 76.2%, P = 0.001). Differences in age of onset, tumor size at diagnosis, and histology may reflect differences in the genetic background of patients with WT between countries, but population-based phenotype-genotype data are lacking. The difference in survival probability for stage IV patients may be due to different diagnostic criteria or different treatment strategies. Prospective, international clinical studies including genomic analyses are needed to confirm these findings and improve clinical practice.


Chamaecyparis obtusa (Siebold & Zucc.) Endl. leaf extracts prevent inflammatory responses via inhibition of the JAK/STAT axis in RAW264.7 cells.
Chamaecyparis obtusa (Siebold & Zucc.) Endl. (C. obtusa) has been used as folk medicine in East Asia and has been reported to alleviate inflammatory diseases. However, the detailed mechanisms for the anti-inflammatory effects of C. obtusa remain unclear. Although the anti-inflammatory mechanisms of natural products have been studied for decades, it is still important to identify the potential anti-inflammatory effects of natural sources. In this study, we investigated the anti-inflammatory effects and underlying mechanism of C. obtusa leaf extracts. The cell viability was determined by MTT and crystal violet staining. NO production in the supernatant was measured using Griess reagent. The cell lysates were analyzed by immunoblotting and RT-qPCR. Secreted cytokines were analyzed using ELISA kit and cytokine array kit. mRNA expression from the GSE9632 database set. Z-scores were calculated for each gene and visualized by heat map. Among the extracts of C. obtusa obtained with different extraction methods, the 99% ethanol leaf extract (CO99EL) strongly inhibited lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and Janus kinase/signaling transducer and activator of transcription (JAK/STAT) phosphorylation in RAW264.7 cells. In addition, CO99EL strongly inhibited LPS-induced interleukin (IL)-1β, IL-6, IL-27, and C-C motif chemokine ligand (CCL)-1 production and directly inhibited LPS-induced JAK/STAT phosphorylation in RAW264.7 cells. These findings demonstrate that CO99EL significantly prevents LPS-induced macrophage activation by inhibiting the JAK/STAT axis. Therefore, we suggest the use of C. obtusa extracts as therapeutic approach for inflammatory diseases.


Magnetic relaxation dispersion probe.
The magnetic field dependence of nuclear spin-lattice relaxation rates provides a powerful approach to characterizing intra and intermolecular dynamics. NMR spectrometers that provide extensive magnetic relaxation dispersion profiles may switch magnetic field strengths rapidly by either moving the sample or by changing the current in an electromagnet. If the sample is moved, the polarization and detection fields may be very high, which provides both high sensitivity and resolution. This report summarizes the design of a pneumatic sample transport system for glass sample containers that may be used in either a dual magnet spectrometer or in a single magnet system that exploits the fringe field as the secondary magnetic field.


Spatiotemporal Insights Into RNA-Organelle Interactions in Neurons.
Neurons exhibit spatial compartmentalization of gene expression where localization of messenger RNAs (mRNAs) to distal processes allows for site-specific distribution of proteins through local translation. Recently, there have been reports of coordination between mRNA transport with vesicular and organellar trafficking. In this review, we will highlight the latest literature on axonal and dendritic local protein synthesis with links to mRNA-organelle cotransport followed by emerging technologies necessary to study these phenomena. Recent high-resolution imaging studies have led to insights into the dynamics of RNA-organelle interactions, and we can now peer into these intricate interactions within subcellular compartments of neurons.


Surgical ablation for atrial fibrillation: impact of Diabetes Mellitus type 2.
Diabetes mellitus (DM) type 2 is an independent risk factor for atrial fibrillation (AF). Surgical ablation or "maze procedure" is an option for patients with AF undergoing concomitant or isolated cardiac surgery. The aim of this study was to evaluate the impact of DM type 2 on early and long-term outcomes of patients following surgical AF ablation. We performed an observational cohort study in Israel's largest tertiary care center. All data of patients who underwent surgical AF ablation, between 2006 and 2021 were extracted from our departmental database. Patients were divided into Group I (non-diabetic patients) and Group II (DM type 2 patients). We compared the two groups with respect to freedom from recurrent atrial arrhythmia, and mortality rate. The study population included 606 patients. Group I (non-DM patients), consisting of 484 patients, and Group II (DM type 2 patients), comprised 122 patients. Patients with DM were older, had more hypertension and incidence of cerebrovascular accident (CVA)/transient ischemic attack (TIA), higher EuroSCORE (p < .05 for all), and a longer bypass time-130 ± 40 vs. 122 ± 36 min (p = 0.028). The mean follow-up duration was 39.0 ± 22.7 months. Freedom from atrial fibrillation was similar between the non-DM and DM type 2 groups after a 1-year follow-up, 414 (88.2%) vs. 101 (87.1%) (p = 0.511), after a 3-year follow-up, 360 (86.3%) vs. 84 (79.9%) (p = 0.290) and after a 5-year follow-up, 226 (74.1%) vs. 55 (71.5%) (p = 0.622) respectively. Furthermore, 1- and 3-year mortality was similar between non-DM and DM type 2 groups, 2.5% vs. 4.9%, (p = 0.226) and 5.6% vs. 10.5% (p = 0.076) respectively. 5-year mortality was higher in Group II (DM type 2 patients) compared with Group I (non-DM patients), 11.1% vs. 23.4% (p = 0.009). Surgical ablation had a high success rate, with freedom from recurrent atrial arrhythmia at 1- 3- and 5- years follow-up in both the DM type 2 and non-DM groups. Furthermore,1- and 3-year mortality after surgical ablation was also similar in both groups. However, 5-year mortality was higher in the DM type 2 group.


Corrigendum to "Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications".
[This corrects the article DOI: 10.1155/2021/9996193.].


Dental Outcomes After Medicaid Insurance Coverage Expansion Under the Affordable Care Act.
Dental coverage for adults is a state option in Medicaid, and despite significant gains in coverage after the Medicaid expansion under the Affordable Care Act (ACA), dental outcomes among adults in expansion states remain unexplored. To explore the association of state coverage of dental benefits through Medicaid expansion with clinical dental outcomes. This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey from 2009 to 2018. Included participants were low-income adults aged 19 to 64 years with income up to 138% of the federal poverty level. The study used a difference-in-differences analysis to compare changes from before to after ACA expansion in expansion states vs in control states. Changes were examined in the full sample and separately in states that did and did not provide Medicaid adult dental benefits. We defined a state as providing Medicaid adult dental benefits if it covered services beyond emergency dental benefits in 2014. Data were analyzed from November 2020 to March 2021. Medicaid expansion under the ACA. Rates of health coverage, having a dental visit, affordability of dental care in the past year, poor oral health, and teeth flossing were obtained from self-reported data. Mean number of missing teeth and prevalence of untreated decayed teeth, filled teeth, and functional dentition were obtained from clinical examination data. Among 7637 low-income adults, the mean (SD) age was 37.8 (13.4) years and 4153 (weighted percentage, 54.5 %) were women. At baseline, 1732 low-income adults in nonexpansion states compared with 2520 low-income adults in expansion states were more likely, as shown by weighted percentage, to be Black (473 individuals [21.0%] vs 508 individuals [15.1%]) and US born (1281 individuals [76.7%] vs 1613 individuals [69.6%]). In the full sample, Medicaid expansion, compared with nonexpansion, was associated with an increased rate of seeing a dentist in the prior year (12.4 percentage points; 95% CI 4.6 to 20.2 percentage points; P = .003). In expansion states that provided dental benefits, compared with nonexpansion states that provided dental benefits, the expansion was associated with increases in rates of Medicaid coverage (8.2 percentage points; 95%CI 0.5 to 15.8 percentage points; P = .04) and having seen a dentist in the previous year (11.4 percentage points, 95% CI, 3.7 to 19.1 percentage points; P = .006) and decreases in the uninsured rate (-12.6 percentage points, 95% CI -18.9 to -6.4 percentage points; P < .001) and prevalence of untreated decayed teeth (-16.8 percentage points; 95% CI, -25.5 to -8.0 percentage points; P = .001). In states without Medicaid dental benefits, the expansion was associated with an increase in the mean number of missing teeth (1.3 teeth; 95% CI 0.1 to 2.5 percentage points; P = .04) and a decrease in the prevalence of functional dentition (-8.7 percentage points; 95% CI, -14.1 to -3.3 percentage points; P = .003) compared with nonexpansion states. This study found that the combination of Medicaid expansion and coverage of Medicaid dental benefits was associated with improved oral health among low-income adults.


Fluorometric techniques for the detection of nitric oxide and metabolites.
Recently fluorometric techniques have been developed to determine NO and S-nitrosothiols with improved sensitivity over spectrophotometric techniques based on similar chemistry. This unit contains protocols for detection and quantification of NO from chemical reactions and from cellular systems, and of S-nitrosothiols in chemical, biochemical, and cellular experiments.


Pelvic floor biometry in asymptomatic primiparous women compared with nulliparous women: a single-center study in Southern China.
This study aimed to investigate pelvic floor biometry of asymptomatic primiparous women compared with nulliparous women by using four-dimensional transperineal ultrasound (4D TPUS). From July 2015 to February 2017, 722 women were enrolled and divided into the nulliparous group (n = 292), the vaginal delivery group (n = 272), and the elective cesarean section group (n = 158). The ultrasound parameters of 4D TPUS were compared among the groups. The vaginal delivery group had a significantly greater bladder neck descent (η2 = 0.04), retrovesical angles on Valsalva maneuver (η2 = 0.01), urethral rotation (η2 = 0.01), levator hiatus area on Valsalva maneuver (η2 = 0.02), urethral inclination angle (η2 = 0.02), and funneling of the proximal urethra (η2 = 0.11) than the other two groups. Comparison of the two modes of delivery (vaginal delivery and cesarean section) also showed significant differences in the above-mentioned ultrasound parameters. There are significant differences in pelvic floor biometry between asymptomatic primiparous women and nulliparous women, as well as between women with vaginal delivery and those with elective cesarean section.


A major root-associated acid phosphatase in Arabidopsis, AtPAP10, is regulated by both local and systemic signals under phosphate starvation.
The induction and secretion of acid phosphatases (APases) is a universal response of plants to phosphate (Pi) starvation. AtPAP10 (Arabidopsis purple acid phosphatase 10) is a major Pi starvation-induced APase that is associated with the root surface in Arabidopsis. So far, the roles of local and systemic signalling in regulating root-associated AtPAP10 activity remain largely unknown. In this work, we show that a decrease of local, external Pi availability is sufficient to induce AtPAP10 transcription in roots in the presence of sucrose, a systemic signal from shoots, whereas the magnitude of the induction is affected by the Pi status of the whole plant. Once the AtPAP10 mRNAs are synthesized in roots, subsequent accumulation of AtPAP10 proteins in root cells and increase in AtPAP10 activity on the root surface are mainly controlled by local signalling. Previously, ethylene has been demonstrated to be a positive regulator of AtPAP10 activity. In this study, we provide evidence that under Pi deficiency ethylene mainly modulates enzymatic activity of AtPAP10 on the root surface, but not AtPAP10 transcription and protein accumulation, suggesting that it functions as a local signal. Furthermore, our work indicates that the effect of ethylene on the induction of root-associated AtPAP10 activity depends on sucrose, but that the effect of sucrose does not depend on ethylene. These results reveal new insights into the distinct roles of local and systemic signalling in the regulation of root-associated AtPAP10 activity under Pi starvation.


Positive correlation between PEDF expression levels and macrophage density in the human prostate.
In this study, we investigated the capacity of pigment epithelium-derived factor (PEDF) to modulate the recruitment and the differentiation of monocytes/macrophages both in vitro and in human prostate. Using Boyden chambers, we assessed PEDF effect on the migration of monocytes and chemically activated RAW 264.7 macrophages. Normal, prostatitis, and prostate cancer specimens were retrospectively selected and examined by immunohistochemistry for PEDF expression and infiltration of immune CD68 + macrophagic cells. PEDF expression and macrophage density were then correlated with each other and clinicopathological parameters. M1 and M2 differentiation markers were quantified by qRT-PCR, Western blotting, and ELISA. In chemotaxis, PEDF induced the migration of monocytes/macrophages. In immunohistochemistry, macrophages were markedly increased in prostatitis and malignant compared to normal tissues. PEDF was expressed at variable levels in the stroma and epithelium. PEDF mRNA was down-regulated in both prostate cancer and prostatitis compared to normal tissues. In correlation studies, macrophage density and PEDF expression were respectively positively and negatively associated with prostate size. Most importantly, PEDF expression positively correlated with macrophage density. Finally, PEDF stimulated the expression of iNOS, IL12, and TNFα; and inhibited IL10 and arginase 1 in mouse and human macrophages confirming a M1-type differentiation. Our data demonstrate that PEDF acts directly on monocytes/macrophages by inducing their migration and differentiation into M1-type cells. These findings suggest a possible role of macrophages in PEDF anti-tumor properties and may support further development of PEDF-based anti-cancer therapy.


A vasa-like gene in zebrafish identifies putative primordial germ cells.
The vasa gene is essential for germline formation in Drosophila. Vasa-related genes have been isolated from several organisms including nematode, frog and mammals. In order to gain insight into the early events in vertebrate germline development, zebrafish was chosen as a model. Two zebrafish vasa-related genes were isolated, pl10a and vlg. The pl10a gene was shown to be widely expressed during embryogenesis. The vlg gene and vasa belong to the same subfamily of RNA helicase encoding genes. Putative maternal vlg transcripts were detected shortly after fertilization and from the blastula stage onwards, expression was restricted to migratory cells most likely to be primordial germ cells.


A reversible defect in natural killer T cell function characterizes the progression of premalignant to malignant multiple myeloma.
We studied the function of antitumor T and natural killer T (NKT) cells from the blood and tumor bed in 23 patients with premalignant gammopathy, nonprogressive myeloma, or progressive multiple myeloma. We show that antitumor killer T cells can be detected in patients with both progressive or nonprogressive myeloma. V alpha 24+V beta 11+ invariant NKT cells are detectable in the blood and tumor bed of all cohorts. However, freshly isolated NKT cells from both the blood and tumor bed of patients with progressive disease, but not nonprogressive myeloma or premalignant gammopathy, have a marked deficiency of ligand-dependent interferon-gamma production. This functional defect can be overcome in vitro using dendritic cells pulsed with the NKT ligand, alpha-galactosylceramide (alpha-GalCer). Fresh myeloma cells express CD1d, and can be efficiently killed by autologous NKT cells. We hypothesize that presentation of tumor derived glycolipids by myeloma cells leads to NKT dysfunction in vivo. These data demonstrate that clinical progression in patients with monoclonal gammopathies is associated with an acquired but potentially reversible defect in NKT cell function and support the possibility that these innate lymphocytes play a role in controlling the malignant growth of this incurable B cell tumor in patients.


Association between stroke and psychosis across four nationally representative psychiatric epidemiological studies.
Both stroke and psychosis are independently associated with high levels of disability. However, psychosis in the context of stroke has been under-researched. To date, there are no general population studies on their joint prevalence and association. To estimate the joint prevalence of stroke and psychosis and their statistical association using nationally representative psychiatric epidemiology studies from two high-income countries (the UK and the USA) and two middle-income countries (Chile and Colombia) and, subsequently, in a combined-countries data-set. Prevalences were calculated with 95% confidence intervals. Statistical associations between stroke and psychosis and between stroke and psychotic symptoms were tested using regression models. Overall estimates were calculated using an individual participant level meta-analysis on the combined-countries data-set. The analysis is available online as a computational notebook. The overall prevalence of probable psychosis in stroke was 3.81% (95% CI 2.34-5.82) and that of stroke in probable psychosis was 3.15% (95% CI 1.94-4.83). The odds ratio of the adjusted association between stroke and probable psychosis was 3.32 (95% CI 2.05-5.38). On the individual symptom level, paranoia, hallucinated voices and thought passivity delusion were associated with stroke in the unadjusted and adjusted analyses. Rates of association between psychosis and stroke suggest there is likely to be a high clinical need group who are under-researched and may be poorly served by existing services.


[Different types of sexual cycles in male European vipers].
Sexual cycles in European male vipers can be divided into two types, Spermatocytogenesis occurs in summer, spermiogenesis and mating in spring in three species. Three other species show more or less continuous spermatogenetic activity, but spermiogenesis occurs mostly in late summer and mating in both autumn and spring.


Nucleotide sequence of 16-kilobase pairs of DNA 5' to the human epsilon-globin gene.
We have determined the nucleotide sequence of a 16-kilobase pair (kb) region of DNA on the 5' side of the human embryonic globin gene (epsilon). This sequence, when combined with previously published sequences, gives an uninterrupted sequence of 21 kb extending from approximately 19.5 kb upstream of the epsilon-globin gene to 0.3 kb 3' to its poly(A)-addition site. Computer-assisted analysis of this DNA reveals no large regions of self-homology but it shows the presence of seven members of the Alu family of repeated DNA, two very short members of the Kpn family of repeated DNA, one unusual direct repeat of 39 base pairs, and two potential stem and loop structures. The overall frequencies of mono- and dinucleotides within the 21 kb approximate those found in the total human genome but the distribution of (G + C)-rich regions signal many sequences of interest. The occurrences of some of the polynucleotides and polydinucleotides also differ appreciably from randomness, and the region contains several large stretches of these simple sequences. We found no evidence of strand asymmetry in the region. Homology between the nucleotide sequences of the human epsilon- and G gamma-globin genes extends only 100 base pairs 5' to the genes. One region, about 10 kb upstream of the gene, shows an apparent clustering of unusual sequence features. We discuss our sequence data in relation to the studies by others of DNAase hypersensitive sites and 5' transcription endpoints in this part of the beta-globin gene cluster.


[Analysis of cellular components in immunocompetent organs treated with ionizing radiations].
The nucleic acid and protein content has been evaluated in lymphoid cells from the thymus and the Bursa of Fabricius of chicks exposed to different doses of radiation. A different response to radiation damage of the two cell populations is suggested by these analysis when compared with ultrastructural data.


Inhibitory potencies of trimipramine and its main metabolites at human monoamine and organic cation transporters.
The antidepressant trimipramine shows an atypical pharmacological profile and its mechanism of action is still obscure. The present study investigated whether trimipramine and three of its metabolites interact with targets of other antidepressants, namely, the human monoamine transporters for noradrenaline (hNAT), serotonin (hSERT), and dopamine (hDAT), and with the human organic cation transporters (hOCT1, hOCT2, and hOCT3) which are expressed in the brain and are known to be involved in the uptake of monoamines. HEK293 cells heterologously expressing the abovementioned transporters were used to determine the inhibition of [(3)H]MPP(+) uptake by trimipramine and its main metabolites. At concentrations up to 30 μM, all transporters, except hOCT3, were inhibited by all examined substances. With IC(50) values between 2 and 10 μM, trimipramine inhibited hSERT, hNAT, hOCT1, and hOCT2, whereas clearly higher concentrations were needed for half-maximal inhibition of hDAT. Desmethyl-trimipramine showed about the same potencies as trimipramine, whereas 2-hydroxy-trimipramine was less potent at hNAT, hSERT, and hOCT1. Trimipramine-N-oxide preferentially inhibited hSERT. Neither trimipramine nor its metabolites are highly potent inhibitors of the examined monoamine transporters. However, since at a steady state the sum of the concentrations of the parent compound and its active metabolites is almost two times higher than the plasma concentration of trimipramine and since it is known that tricyclic antidepressants accumulate in the brain (up to tenfold), at least partial inhibition by trimipramine and its metabolites of hSERT and hNAT (but not of hOCT3) may contribute to the antidepressant action of trimipramine.


The effects of maternally administered magnesium sulfate on the neonate.
The effects of parenterally administered magnesium sulfate on maternal and neonatal calcium and magnesium metabolism in nonasphyxiated, term pregnancies complicated by pregnancy-induced hypertension were studied prospectively. In addition, the neurobehavioral effects of neonatal hypermagnesemia were investigated by means of a neonatal assessment scale that specifically measures reflex activity and both passive and active muscle tone. Maternal magnesium sulfate infusion was associated with maternal and neonatal hypermagnesemia when compared with that of control subjects (1.8 +/- 0.10 to 3.6 +/- 0.5 mg/dl, p less than 0.001, and 1.75 +/- 0.2 to 3.6 +/- 0.5 mg/dl, p less than 0.005, respectively). Maternal serum calcium levels fell with magnesium therapy (9.3 +/- 0.18 to 7.9 +/- 0.1 mg/dl, p less than 0.001), while neonatal calcium levels were unaffected (10.8 +/- 0.44 to 10.5 +/- 0.38 mg/dl, p less than 0.05). Neurological status examinations in the neonate were similar in both the control and treatment groups. In addition, neurological performance of the neonate did not correlate with cord magnesium levels or to the total dose of magnesium administered.


Advanced in silico validation framework for three-dimensional traction force microscopy and application to an in vitro model of sprouting angiogenesis.
In the last decade, cellular forces in three-dimensional hydrogels that mimic the extracellular matrix have been calculated by means of Traction Force Microscopy (TFM). However, characterizing the accuracy limits of a traction recovery method is critical to avoid obscuring physiological information due to traction recovery errors. So far, 3D TFM algorithms have only been validated using simplified cell geometries, bypassing image processing steps or arbitrarily simulating focal adhesions. Moreover, it is still uncertain which of the two common traction recovery methods, i.e., forward and inverse, is more robust against the inherent challenges of 3D TFM. In this work, we established an advanced in silico validation framework that is applicable to any 3D TFM experimental setup and that can be used to correctly couple the experimental and computational aspects of 3D TFM. Advancements relate to the simultaneous incorporation of complex cell geometries, simulation of microscopy images of varying bead densities and different focal adhesion sizes and distributions. By measuring the traction recovery error with respect to ground truth solutions, we found that while highest traction recovery errors occur for cases with sparse and small focal adhesions, our implementation of the inverse method improves two-fold the accuracy with respect to the forward method (average error of 23% vs. 50%). This advantage was further supported by recovering cellular tractions around angiogenic sprouts in an in vitro model of angiogenesis. The inverse method recovered higher traction peaks and a clearer pulling pattern at the sprout protrusion tips than the forward method. STATEMENT OF SIGNIFICANCE: Biomaterial performance is often studied by quantifying cell-matrix mechanical interactions by means of Traction Force Microscopy (TFM). However, 3D TFM algorithms are often validated in simplified scenarios, which do not allow to fully assess errors that could obscure physiological information. Here, we established an advanced in silico validation framework that mimics real TFM experimental conditions and that characterizes the expected errors of a 3D TFM workflow. We apply this framework to demonstrate the enhanced accuracy of a novel inverse traction recovery method that is illustrated in the context of an in vitro model of sprouting angiogenesis. Together, our study shows the importance of a proper traction recovery method to minimise errors and the need for an advanced framework to assess those errors.


Cement removal in revision hip arthroplasty. Experience with bone cement added to the cavity in 20 cases.
A new technique for cement removal is presented where bone cement is added to the cavity after removal of a femoral component. The old and new segments of cement are then removed together by using a threaded extractor. In 16 of 20 patients, the method was successful; the entire cement mass was extracted in 35 (25-50) min without complications or bone loss. In 4 of the patients, the technique had to be combined with traditional methods for cement removal.


Load effects of thigh wearable resistance on angular and linear kinematics and kinetics during non-motorised treadmill sprint-running.
The aim of this study was to investigate the load effects of thigh attached wearable resistance (WR) on linear and angular kinematics and linear kinetics during sprint-running. Fourteen recreational active subjects performed a series of maximal sprints with and without WR of 1%, 2%, and 3% body mass (BM) in a randomised order. Sprints were performed on a non-motorised treadmill that collected velocity, and linear step kinematics and kinetics. Angular kinematics of the thigh were collected from an inertial measurement unit attached to the left thigh. Trivial decreases were found in peak velocity with all WR loads (-0.9 to -.2.4%, effect size [ES] 0.09-0.17, p > .05). The WR conditions resulted in significantly decreased average step frequency (-2.0% to -3.0%, ES = 0.35-0.44, p < .05) with loads of ≥2% BM, whereas average step length was statistically unchanged (1.9-2.8%, ES = 0.20-0.33). Average angular displacement was significantly decreased (-7.0% to -10.3%, ES = 0.88-1.10, p = 0.00-0.03) with loads of ≥2% BM. Average angular flexion velocity (-10.2%, ES = 1.07, p = .02) and extension velocity (-12.0%, ES = 0.85, p = .01) were significantly decreased with 3% BM. Trivial to small ES changes (p > .05) were found in the linear kinetic measures of interest. Thigh WR provides a sprint-specific rotational form of resistance resulting in greater changes to angular kinematics than linear properties of sprint-running. For practitioners who wish to target thigh angular kinematics and step frequency without decreasing step length, thigh WR of ≥2% BM offers a sprint-specific resistance training tool.


Factors associated with viral RNA shedding and evaluation of potential viral infectivity at returning to school in influenza outpatients after treatment with baloxavir marboxil and neuraminidase inhibitors during 2013/2014-2019/2020 seasons in Japan: an observational study.
This study assessed the differences in daily virus reduction and the residual infectivity after the recommended home stay period in Japan in patients infected with influenza and treated with baloxavir (BA), laninamivir (LA), oseltamivir (OS), and zanamivir (ZA). We conducted an observational study on children and adults at 13 outpatient clinics in 11 prefectures in Japan during seven influenza seasons from 2013/2014 to 2019/2020. Virus samples were collected twice from influenza rapid test-positive patients at the first and second visit 4-5 days after the start of treatment. The viral RNA shedding was quantified using quantitative RT-PCR. Neuraminidase (NA) and polymerase acidic (PA) variant viruses that reduce susceptibility to NA inhibitors and BA, respectively, were screened using RT-PCR and genetic sequencing. Daily estimated viral reduction was evaluated using univariate and multivariate analyses for the factors such as age, treatment, vaccination status, or the emergence of PA or NA variants. The potential infectivity of the viral RNA shedding at the second visit samples was determined using the Receiver Operator Curve based on the positivity of virus isolation. Among 518 patients, 465 (80.0%) and 116 (20.0%) were infected with influenza A (189 with BA, 58 with LA, 181 with OS, 37 with ZA) and influenza B (39 with BA, 10 with LA, 52 with OS, 15 with ZA). The emergence of 21 PA variants in influenza A was detected after BA treatment, but NA variants were not detected after NAIs treatment. Multiple linear regression analysis showed that the daily viral RNA shedding reduction in patients was slower in the two NAIs (OS and LA) than in BA, influenza B infection, aged 0-5 years, or the emergence of PA variants. The residual viral RNA shedding potentially infectious was detected in approximately 10-30% of the patients aged 6-18 years after five days of onset. Viral clearance differed by age, type of influenza, choice of treatment, and susceptibility to BA. Additionally, the recommended homestay period in Japan seemed insufficient, but reduced viral spread to some extent since most school-age patients became non-infectious after 5 days of onset.


Enhancement of the responses of human colon adenocarcinoma cells to X-irradiation and cis-platinum by N-methylformamide (NMF).
The ability of the maturational agent N-methylformamide (NMF) to modify the response of exponentially growing clone A human colon adenocarcinoma cells to x-irradiation, cis-platinum (cis-DDP), or x-irradiation combined with cis-platinum was studied using an in vitro clonogenic assay. When clone A tumor cells were adaptively grown in medium containing 1% NMF (V/V) for 3 passages prior to experiments, a significantly increased sensitivity to x-irradiation as compared to non-NMF treated cells was found. This increased sensitivity was most marked in the low dose region of the survival curve (as indicated by a large increase in the alpha constant in the linear-quadratic equation), and is similar to the increased radiosensitivity observed after treatment of these tumor cells with N,N-dimethylformamide (DMF). Growth in NMF medium also sensitized these cells to the cytotoxic effects of a 1 hr treatment with cis-DDP at 37 degrees C. A dose enhancement factor of about 1.8 was found at the 10% level of survival for the NMF adapted and cis-DDP treated cells as compared to control cells. Clone A cells were treated either immediately prior to or immediately after x-irradiation with a single low dose of cis-DDP (1.5 microgram/ml, 1 hour at 37 degrees C) after adaptation to growth in NMF containing medium, and the modification of the X ray survival curve was compared to cells not exposed to NMF and to NMF-treated cells also treated with cis-DDP. For the non-NMF treated cells, the low dose cis-DDP treatment produced no change in the survival parameters of the X ray survival curve. However, the NMF adapted cells exhibited an additional decrement in cell survival, indicating that the effect of NMF on radiation on cis-DDP cell killing was additive in nature when all 3 agents were combined in this protocol. Also, there was no difference between the sequences of cis-DDP (1 hr, 37 degrees C) + X rays versus X rays + cis-DDP (1 hr, 37 degrees C). These data indicate that combinations of differentiation inducing agents, together with chemotherapeutic agents and X rays, may be a promising avenue of investigation in developing strategies for cancer treatment.


Bisphenol A induced toxicity in blood cells of freshwater fish Channa punctatus after acute exposure.
The widespread use of bisphenol A (BPA) has led to its ubiquity in the natural environment. It is extensively incorporated into different industrial products and is associated with deleterious health effects on both public and wildlife. The current trial was conducted to determine the toxic potential of bisphenol A using various parameters viz haematological, biochemical, and cytological in freshwater fish Channa punctatus. For this purpose, fish were exposed to 1.81 mg/l (1/4 of LC50) and 3.81 mg/l (1/2 of LC50) of BPA along with positive (acetone) and negative controls (water) for 96 h. The blood samples were collected at 24, 48, 72, and 96 h post-exposure. Compared to the control group, fish after acute exposure to BPA showed a significant decrease in HB content, number of red blood cells, PCV values whereas a significant increase in WBCs count was recorded with an increase in the exposure period. Besides, oxidative stress (determined as malondialdehyde content) increased as BPA concentration increased. Further, the activity of different antioxidant enzymes like catalase, and superoxide dismutase decreased significantly after treatment. Results also showed significantly increased frequency of morphological alterations, nuclear changes, and increased DNA damage potential of BPA in red blood cells. Further structural analysis of erythrocytes in maximally damaged group using Scanning Electron Microscopy was performed. The study concludes that BPA exhibits genotoxic activity and oxidative stress could be one of the mechanisms leading to genetic toxicity.


Toothbrushing frequency and gastric and upper aerodigestive tract cancer risk: A meta-analysis.
Results of epidemiological studies evaluating the association between toothbrushing and gastric and upper aerodigestive tract (UADT) cancer risk showed inconsistent results. The purpose of this study was to evaluate the association between toothbrushing and gastric and UADT cancer risk and quantify the dose-response association between them. We searched the PubMed, EMBASE and Cochrane Library databases to identify relevant studies on toothbrushing and gastric and UADT cancer risk. Statistical analyses were performed using STATA 12.0 software. A total of 30 studies of involving 1 194 017 participants met eligibility criteria and were included in the meta-analysis. Meta-analysis using a random-effect model showed that the high frequency of toothbrushing was associated with significantly reduced risk of gastric and UADT cancers (OR: 0.55, 95% CI 0.46-0.64, P < .05). Our dose-response analysis presented that every increased toothbrushing per day might reduce oral cavity cancer risk by 6%, pharyngeal cancer risk by 11%, laryngeal cancer risk by 3%, oesophageal cancer risk by 6% and gastric cancer risk by 4%. This meta-analysis suggested the negative relationship between frequency of toothbrushing and risk of gastric and UADT cancers. Toothbrushing may be a protective factor for gastric and UADT cancers. However, this association must be further validated through large prospective studies.


Toxicokinetics and toxicodynamics of ochratoxin A, an update.
Ochratoxin A (OTA) is a mycotoxin produced by fungi of two genera: Penicillium and Aspergillus. OTA has been shown to be nephrotoxic, hepatotoxic, teratogenic and immunotoxic to several species of animals and to cause kidney and liver tumours in mice and rats. Because of differences in the physiology of animal species, wide variations are seen in the toxicokinetic patterns of absorption, distribution and elimination of the toxin. Biotransformation of OTA has not been entirely elucidated. At present, data regarding OTA metabolism are controversial. Several metabolites have been characterized in vitro and/or in vivo, whereas other metabolites remain to be characterized. Several major mechanisms have been shown as involved in the toxicity of OTA: inhibition of protein synthesis, promotion of membrane peroxidation, disruption of calcium homeostasis, inhibition of mitochondrial respiration and DNA damage. The contribution of metabolites in OTA genotoxicity and carcinogenicity is still unclear. The genotoxic status of OTA is still controversial because contradictory results were obtained in various microbial and mammalian tests, notably regarding the formation of DNA adducts. More recent studies are focused on the OTA ability to disturb cellular signalling and regulation, to modulate physiological signals and thereby to influence cells viability and proliferation. The present paper offers an update on these different issues. In addition since humans and animals are likely to be simultaneously exposed to several mycotoxins, especially through their diet, the little information available on the combined effects of OTA and other mycotoxins has also been reviewed.


The role of G protein-coupled estrogen receptor 1 on neurological disorders.
G protein-coupled estrogen receptor 1 (GPER) is a membrane-associated estrogen receptor (ER) associated with rapid estrogen-mediated effects. Over recent years GPER emerged has a potential therapeutic target to induce neuroprotection, avoiding the side effects elicited by the activation of classical ERs. The putative neuroprotection triggered by GPER selective activation was demonstrated in mood disorders, Alzheimer's disease or Parkinson's disease of male and female in vivo rodent models. In others, like ischemic stroke, the results are contradictory and currently there is no consensus on the role played by this receptor. However, it seems clear that sex is a biological variable that may impact the results. The major objective of this review is to provide an overview about the physiological effects of GPER in the brain and its putative contribution in neurodegenerative disorders, discussing the data about the signaling pathways involved, as well as, the diverse effects observed.


Selective transfer of calcium from an acidic compartment to the mitochondrion of Trypanosoma brucei. Measurements with targeted aequorins.
Organelle compartments are used by cells as reservoirs of exchangeable Ca2+ and as Ca2+ buffers. The following study uses recombinant aequorins (CYT-AEQ and MT-AEQ) to measure the dynamics of Ca2+ flux between organelles in procyclic forms of the pathogenic protozoan, Trypanosoma brucei. Emphasis is placed on the exchange between an acidic Ca2+ reservoir and the mitochondrion. The mammalian mitochondrial targeting sequence was functional in trypanosomes as determined by immunoblots, immunolocalizations, and the observation that MT-AEQ was in a compartment whose Ca2+ uptake was inhibited 82% with carbonyl cyanide p-trifluoromethoxyphenylhydrazone and KCN. The resting level of free calcium ion concentration in the mitochondrion ([Ca2+]mit) was slightly higher than that in the cytoplasm ([Ca2+]cyt) (400 +/- 50 nM and 290 +/- 40 nM, respectively). Melittin (125 nM) disrupted Ca2+ homeostasis by inducing Ca2+ influx across the plasma membrane. [Ca2+]cyt became slightly elevated to 410 +/- 100 nM, whereas [Ca2+]mit was selectively increased approximately 12-fold, with a broad peak at 4.8 +/- 1.9 microM. At the peak, the mitochondrion contained approximately three times more free Ca2+ than the cytosol. However, mitochondrial retention of the Ca2+ was transient. Similar selective transport into the mitochondrion was observed when Ca2+ efflux from an acidic compartment was induced with monensin (2 microg/ml) in the presence of 5 mM EGTA. [Ca2+]cyt was transiently elevated to 400 +/- 50 nM, whereas [Ca2+]mit was elevated to 3.3+/-1.3 microM. When cells were treated sequentially with monensin (2 microg/ml) and then melittin (200 nM), mitochondrial Ca2+ transport was normal. However, [Ca2+]cyt became elevated to a level that was 1.4-fold higher than with melittin alone. Overall, these data demonstrate that the trypanosome mitochondrion is not a reservoir of exchangeable Ca2+ in the resting cell. However, Ca2+ is selectively channeled to the mitochondrion from the plasma membrane or acidic Ca2+ storage compartment. Additionally, the acidic compartment contributes to maintenance of Ca2+ homeostasis in response to melittin.


[Chronic bronchitis and respiratory capacity of the lungs in miners from a specific coal mine].
In the group of 3317 miners of one coal mine, who were employed for over 8 years, the prevalence of chronic bronchitis (ch.b.) and lung ventilation disorders was analysed. The frequency of ch.b. in the subjects under study was almost twice as high as in the general male population in Poland and significantly more frequent in miners with pneumoconiosis than in those without pneumoconiosis. Simple pneumoconiosis and ch.b. contributed to decreased ventilatory capacity of the lung.


The relationship between the Neuro-Quality of Life Depression and Anxiety Measures and the Personality Assessment Inventory in persons with epilepsy.
To investigate the associations between the Neuro-Quality of Life (NQOL) Depression and Anxiety measures with an objective emotional inventory (Personality Assessment Inventory; PAI), and demonstrate the clinical utility of the NQOL as screening measures for depression and anxiety in persons with epilepsy (PWE). PWE (N=72) were concurrently administered the NQOL Depression and Anxiety measures and the PAI. Pearson product moment correlations were used to determine the relationships between the NQOL measures and the respective PAI scales (i.e., depression, anxiety). One-way ANOVAs were conducted comparing NQOL scores between patients with elevated levels of depression and anxiety (T-score≥65 on the PAI) to profiles that were within normal limits. Using sensitivity and specificity analyses, optimal cut-scores on the NQOL measures were determined. Participants were primarily Caucasian (89%), female (60%), and ~35 years old. The NQOL Depression measure was significantly correlated with the PAI Depression total score (r=.747; p<0.001) and its subscales (p's<0.001). Similarly, the NQOL Anxiety measure was significantly correlated with the PAI Anxiety total score (r=.750; p<0.001) and its subscales (p's<0.001). Compared to profiles that were within normal limits, individuals with elevated depressive symptoms on the PAI had significantly higher NQOL Depression scores (F(1,71)=48.2, p<0.001, d=1.6). Similarly, those who endorsed elevated anxiety on the PAI had significantly higher NQOL Anxiety scores (F(1,71)=32.2, p<0.001, d=1.5). Cut-off scores of 19 on the NQOL Depression and 24 on the NQOL Anxiety measures adequately detected depression (sensitivity=0.67; specificity=0.93; PPV=0.91; NPV=0.74) and anxiety symptoms (sensitivity=0.77; specificity=0.82; PPV=0.81; NPV=0.78) in PWE. The NQOL Depression and Anxiety measures evidenced strong associations with the PAI Depression and Anxiety scales and may be effective in detecting depressive and anxiety symptoms in PWE using the provided cut-scores.


Psychophysiology-informed (multimodal) imaging.
Electroencephalography (EEG) and magnetic resonance imaging are two popular methodologies for brain research. While EEG has a high temporal resolution, yet a low spatial resolution, MRI has the complete opposite, a high spatial resolution, yet a low temporal resolution. Obviously therefore, researchers have been searching for ways combining the two methodologies, for more than two decades. However, there are many issues that have to be solved before the methodologies can be successfully and, more importantly reliably, combined. Here, we give an overview of these issues, and present strategies that have been used over the past two decades to overcome them. We start with a general description of EEG and (f)MRI methodology, then present the difficulties involved in combining both methodologies, and lastly present and discuss the most popular strategies that have been used over the past two decades to solve these problems. We conclude that in spite of the many issues, the two methodologies can be combined successfully, provided that the correct procedures are followed.


Entropic shrinkage of an oxide glass.
Entropic elasticity, a property typical of rubbers and well known in organic polymers with appropriate network structures, is not known to occur in oxide glasses. Here, we report the occurrence of entropic elasticity in phosphate-glass fibres with highly anisotropic structures, drawn by mechanical elongation from supercooled liquids. We observed a large lengthwise shrinkage of ~35% for phosphate glasses with an enhanced one-dimensional structure, as well as a distinct endotherm on reheating them up to temperatures between that of the glass transition temperature and the softening temperature. Our results strongly suggest the possibility of designing oxide glasses with a rubbery nature at high temperatures.


Identification of new marker genes from plant single-cell RNA-seq data using interpretable machine learning methods.
An essential step in the analysis of single-cell RNA sequencing data is to classify cells into specific cell types using marker genes. In this study, we have developed a machine learning pipeline called single-cell predictive marker (SPmarker) to identify novel cell-type marker genes in the Arabidopsis root. Unlike traditional approaches, our method uses interpretable machine learning models to select marker genes. We have demonstrated that our method can: assign cell types based on cells that were labelled using published methods; project cell types identified by trajectory analysis from one data set to other data sets; and assign cell types based on internal GFP markers. Using SPmarker, we have identified hundreds of new marker genes that were not identified before. As compared to known marker genes, the new marker genes have more orthologous genes identifiable in the corresponding rice single-cell clusters. The new root hair marker genes also include 172 genes with orthologs expressed in root hair cells in five non-Arabidopsis species, which expands the number of marker genes for this cell type by 35-154%. Our results represent a new approach to identifying cell-type marker genes from scRNA-seq data and pave the way for cross-species mapping of scRNA-seq data in plants.


Binding site analysis of potential protease inhibitors of COVID-19 using AutoDock.
Recent outbreak of COVID-19 caused by SARS-CoV-2 in December 2019 raised global health concerns. Re-purposing the available protease inhibitor drugs for immediate use in treatment in SARS-CoV-2 infections could improve the currently available clinical management. The current study, aims to predict theoretical structure for protease of COVID-19 and to explore further whether this protein can serve as a target for protease inhibitor drugs such as remdesivir, nelfinavir, lopinavir, ritonavir and α-ketoamide. While the 3D structure of protease was predicted using SWISS MODEL server, molecular interaction studies between protein and ligands were performed using AutoDock software. The predicted protease model was reasonably good based on reports generated by different validation servers. The study further revealed that all the protease inhibitor drugs got docked with negative dock energy onto the target protein. Molecular interaction studies showed that protease structure had multiple active site residues for remdesivir, while for remaining ligands the structure had only one active site residue each. From the output of multiple sequence alignment, it is evident that ligand binding sites were conserved. The current in silico study thus, provides structural insights about the protease of COVID-19 and also its molecular interactions with some of the known protease inhibitors.


Facile synthesis of PbWO4: applications in photoluminescence and photocatalytic degradation of organic dyes under visible light.
Stolzite polymorph of PbWO4 catalyst was prepared by the facile room temperature precipitation method. Structural parameters were refined by the Rietveld analysis using powder X-ray data. PbWO4 was crystallized in the scheelite-type tetragonal structure with space group I41/a (No. 88). Field emission scanning electron microscopy revealed leaf like morphology. Photoluminescence spectra exhibit broad blue emission (425 nm) under the excitation of 356 nm. The photocatalytic degradation of Methylene blue, Rhodamine B and Methyl orange dyes were measured under visible illumination. The 100% dye degradation was observed for MB and RhB dyes within 60 and 105 min. The rate constant was found to be in the decreasing order of MB>RhB>MO which followed the 1st order kinetic mechanism. Therefore, PbWO4 can be a potential candidate for blue component in white LEDs and also acts as a catalyst for the treatment of toxic and non-biodegradable organic pollutants in water.


Granulocyte-macrophage progenitor cells in term and preterm neonates.
In groups of adults, and term and preterm neonates, we determined: the blood concentration, the proliferative rate, and the variety of progeny of committed granulocyte-macrophage progenitor cells (CFU-GM). In five of eight term neonates and in all premature infants, a potentially significant limitation of neutrophil production was detected. Unlike the slowly proliferating CFU-GM present in the blood of healthy adult subjects (7% thymidine suicide, range 0% to 32%), the circulating CFU-GM in the premature subjects were proliferating at a near maximal rate (55%, range 40% to 75%, P less than 0.001). Because CFU-GM proliferation is nearly maximal in the baseline, noninfected state, neonates may have restricted ability to increase neutrophil production from CFU-GM during times of increased neutrophil need, such as during bacterial infection. Such inability may predispose neonates to exhaustion of the neutrophil supply during bacterial infection.


Mediation of the actions of insulin and insulin-like growth factor-1 on preimplantation mouse embryos in vitro.
Previous studies showed that both insulin and insulin-like growth factor-1 (IGF-1) stimulate metabolism and growth of preimplantation embryos. Because the effects of insulin occur with very low doses, it was suggested that its effects were mediated by its own receptors. However, the effects of IGF-1 occurred at higher doses, suggestive of cross reaction with the insulin receptor but still in the range for mediation via its own receptor. The aim of this study was to investigate the mediation of the metabolic and growth effects of insulin and IGF-1 using a specific insulin receptor antagonist. The antagonistic B-10 Fab fragment (B-10f) completely blocked stimulation of protein synthesis by both insulin and IGF-1, indicating that the insulin receptor mediates this action of both hormones. Alternately, only insulin's stimulation of inner cell mass mitogenesis and morphological development was inhibited by the B-10 Fab fragment. This showed that growth stimulation by insulin and IGF-1 was mediated via different receptors, insulin through its own receptor and IGF-1 through some other receptor. However, mediation via the IGF-2 receptor is not excluded since IGF-1 stimulates compaction when there is evidence for only the presence of the IGF-2 receptor. In summary, insulin or IGF-1 at physiological concentrations stimulates preimplantation mouse embryos, suggesting an important role for both these growth factors in early development.


Inhibition of the chemokine (C-C motif) ligand 2/chemokine (C-C motif) receptor 2 pathway attenuates hyperglycaemia and inflammation in a mouse model of hepatic steatosis and lipoatrophy.
Using a mouse model of lipoatrophic diabetes, we hypothesised that the chemokine (C-C motif) ligand 2 (CCL2)/chemokine (C-C motif) receptor 2 (CCR2) pathway contributes to hepatic macrophage accumulation and insulin resistance through induction of a chronic inflammatory state. Metabolic variables of insulin resistance and inflammation were characterised in wild-type and lipoatrophic A-ZIP/F-1 transgenic (AZIP-Tg) mice. The AZIP-Tg mice were then treated with a CCR2 antagonist (RS504393, 2 mg kg(-1) day(-1)) or vehicle for 28 days via a subcutaneous mini-osmotic pump to examine the role of the CCL2/CCR2 pathway in lipoatrophic diabetes. The lipoatrophic AZIP-Tg mice were diabetic with high fasting glucose and serum insulin concentrations compared with littermate controls. The livers of AZIP-Tg mice were more than threefold enlarged and exhibited increased triacylglycerol content. CCL2 levels were highly elevated in both liver and serum of the AZIP-Tg mice compared with controls. In addition, the circulating CCL2 concentration was associated with increased macrophage accumulation and inflammation as documented by upregulation of Cd68 gene and Tnf-alpha [also known as Tnf] gene in livers from the AZIP-Tg mice. Treatment of the lipoatrophic AZIP-Tg mice with the CCR2 antagonist ameliorated the hyperglycaemia, hyperinsulinaemia and hepatomegaly in conjunction with a reduction in liver inflammation. These findings demonstrate a significant role of the CCL2/CCR2 pathway in lipoatrophy-induced diabetes and provide clear evidence that metabolic improvements resulting from the inhibition of this inflammatory pathway are not adipose tissue-dependent.


The clinical applicability of the Self-Appraisal of Illness Questionnaire (SAIQ) to chronic schizophrenic patients in Taiwan.
Over the last decade, several self-report instruments to assess insight of illness from schizophrenic patients' perspectives have been administered. The main purpose of this study was to ascertain the reliability and validity of the Taiwanese version of the Self-Appraisal of Illness Questionnaire (SAIQ) in a chronic schizophrenic sample in Taiwan. This scale is a self-administered instrument designed to evaluate attitudes toward mental illness among patients receiving treatment. In the current cross-sectional study, 104 patients who met DSM-IV criteria for schizophrenic disorders were recruited and independently interviewed. The psychometric properties of the translated SAIQ were determined, including internal consistency, test-retest reliability, and construct validity. In addition, we analyzed psychosocial and clinical characteristics as correlates of the Taiwanese version of the SAIQ. Overall, the Taiwanese version of the SAIQ was found to be internally consistent and reliable over time. This translated scale comprised a three-factor solution with factors corresponding to worry, the need for treatment, and presence/outcome subscales. The results also indicated that the three subscales and its total score were significantly associated with both the research-rated insight scale and psychopathology and mood state. This culture-specific study shows that the Taiwanese version of the SAIQ is a simple and reliable scale for use.


Verruciform xanthoma coexisting with oral discoid lupus erythematosus.
We describe an unusual case of verruciform xanthoma on the lingual surface of the gum that coexisted with oral discoid lupus erythematosus.