First trimester maternal BMI is a positive predictor of cord blood c-peptide levels while maternal visfatin levels is a negative predictor of birth weight.
The role of first trimester maternal body mass index (BMI) and adipocytokines in cord blood c-peptide and birth weight in pregnancy was investigated. Seventy non-diabetic pregnant Caucasian women were recruited. Anthropometry and measurements of fasting adipocytokines (visfatin, leptin, adiponectin), insulin and glucose were performed in each of the three trimesters. At birth, birth weight and cord blood c-peptide, glucose, insulin, visfatin, leptin, adiponectin and IL6 in each neonate were measured. First trimester maternal BMI correlated positively with cord blood c-peptide (p=0.035, r=0.74) and negatively with cord blood visfatin (p=0.049, r=-0.67). First trimester HOMAR was negatively correlated with cord blood visfatin (p=0.037, r=-0.90) and negatively with cord blood leptin (p=0.031, r=0.90). First trimester maternal BMI was a positive predictor of cord blood c-peptide (p=0.007). First trimester maternal visfatin levels were negative predictors of birth weight (p=0.017). We conclude that first trimester maternal BMI and serum visfatin seem to be strongly associated with fetal insulin secretion and final birth weight, respectively, suggesting a role of early-pregnancy maternal adipose tissue in the pregnancy metabolic environment.


Preface to the Special Issue "Glutathione: Chemistry and Biochemistry".
This year we celebrate the 135th anniversary of the discovery of glutathione (L-γ-glutamyl-L-cysteinyl-glycine) [...].


Calcified renal artery aneurism embolization in a solitary kidney.
To review presentation, diagnosis and treatment of renal artery aneurysms, a very uncommon disease. We report the case of a male with a calcified renal artery aneurysm in a solitary kidney. Symptomatic effects may be hypertension, hematuria or flank pain. Arteriosclerosis and medial dysplasia are the most frequent causes and diagnosis is based on CT scan and angiography. The renal artery aneurysm is a disease with low prevalence and there is no clear protocol for management. The number of cases has increased over the last decades and endovasculrar treatment is a good therapeutic option.


Pubic osteomyelitis resulting in rectovaginal fistula in an adolescent female.
Pelvic osteomyelitis is a rare but serious condition that has the potential for systemic and muscular complications if left untreated. The diagnosis is difficult due to the relative rarity of the disease, the difficulty of localizing the site of the infection, and the tendency for the presentation to mimic other disease processes. A 13-year-old female who presented with complaint of severe right lower abdominal pain thought to be related to a hemorrhagic cyst but was found to have pubic osteomyelitis resulting in an abscess and vaginal fistula. Although rare, pelvic osteomyelitis should be included in the differential diagnosis of pelvic pain.


Head-shaking nystagmus in patients with unilateral peripheral vestibular lesions.
In certain patients with peripheral or central vestibular lesions, a transient nystagmus appears after shaking the head rapidly for 10 to 20 cycles. We recorded such a "head-shaking nystagmus" using the scleral eye coil in six subjects with unilateral peripheral vestibular lesions. Horizontal head shaking elicited horizontal nystagmus with slow phases that were initially directed toward the side of the lesion and upward. All subjects showed a prolonged, lower-amplitude reversal phase after the initial response following horizontal head shaking. The main features of these results can be explained by an analytic model that incorporates a central velocity-storage mechanism that perseverates vestibular inputs, Ewald's second law, and adaptation of primary vestibular afferent activity.


Interaction between Eimeria uzura infection and aflatoxicosis in Japanese quail (Coturnix coturnix japonica).
The clinical signs and gross lesions caused by Eimeria uzura (10(5) oocysts) in Japanese quail (Coturnix coturnix japonica) exhibited little or no influence in the face of intercurrent dietary aflatoxicosis (1 p.p.m. of aflatoxin B1 from Day 0 to 55). Similarly, no significant differences in the mucosal morphology of the intestine were evident histologically between the two groups of Japanese quail. The nervous signs of ataxia, leg weakness, incoordination of movement, torticollis and terminal opisthotonos were toxin-induced manifestations. In the aflatoxic quail, hypoplastic changes and selective depletion of lymphocytes were more prominent in the bursa of fabricius. Increased relative mean weights of liver, kidney, spleen, crop, proventriculus and gizzard were observed in birds due to aflatoxin sensitivity. The combination of E. uzura infection and aflatoxicosis in Japanese quail may cause significant weight loss, and increased oocyst production and reproductive potential.


Carotid IMT and Stiffness in the KiGGS 2 National Survey: Third-Generation Measurement, Quality Algorithms and Determinants of Completeness.
Carotid intima-media thickness (cIMT) and carotid stiffness (CS) are important markers of atherosclerotic risk in the young. We assessed a novel third-generation method for its applicability in large population-based epidemiologic studies to determine strengths, limitations, completeness and predictors of unsuccessful measurement. Four thousand seven hundred ninety-eight 14- to 31-y-old participants of the German KiGGS cohort, which is based on a nationally representative sample with 11-y follow-up, underwent B-mode ultrasound examinations of the left and right common carotid artery with semi-automatic edge detection and automatic electrocardiogram-gated real-time quality control based on a sophisticated snake algorithm and subpixel interpolation. Overall completeness was 98% for far wall cIMT and 89% for CS parameters. Plane-specific completeness varied from 92%-96% for far wall and from 64%-69% for near-wall cIMT. Obesity independently predicted unsuccessful cIMT and CS measurements with odds ratios of 12.67 (95% confidence interval: 5.50-29.19) and 7.30 (4.87-10.94) compared with non-overweight after adjustment for blood pressure, cholesterol, smoking, hazardous drinking, age, sex and sonographer. Inter- and intra-rater reliabilities of cIMT and CS parameters in a sample of 15 young adults were good or excellent. Third-generation cIMT and CS measurements in the young with semi-automatic edge-detection and automatic real-time quality control has been successfully standardized with high reliability and very high completeness in a national survey setting. This provides a strong methodological foundation for further validation of the predictive value of cIMT and CS for atherosclerotic risk in the young.


Synergistic antithrombotic effects of argatroban and ticlopidine in the rat venous thrombosis model.
Argatroban, a synthetic thrombin inhibitor, and ticlopidine, an anti-platelet agent, are major antithrombotic agents. We investigated the antithrombotic effects of a combination of argatroban and ticlopidine in the rat venous thrombosis model. Argatroban or ticlopidine inhibited thrombus formation in a dose-dependent manner; 50% inhibition (ED50) is obtained with 1.0 mg/kg/h (infusion) argatroban or 30 mg/kg (p.o.) ticlopidine. The combination of argatroban and ticlopidine inhibited thrombus formation in a dose-dependent manner; ED50 is obtained with 0.25 mg/kg/h argatroban plus 10 mg/kg ticlopidine and 0.5 mg/kg/h argatroban plus 3 mg/kg ticlopidine, whereas 0.5 mg/kg/h argatroban alone or 10 mg/kg ticlopidine alone had negligible effect (<20% inhibition). Isobole analysis showed that the antithrombotic effects of the combination of argatroban and ticlopidine involved synergism with potentiation. In contrast, the combination of argatroban and ticlopidine did not prolong the bleeding time synergistically. These data showed that the combination therapy of argatroban and ticlopidine should be clinically beneficial, but the different administration route may restrict the clinical usage.


Comparison the Marginal and Internal Fit of Metal Copings Cast from Wax Patterns Fabricated by CAD/CAM and Conventional Wax up Techniques.
Metal-ceramic crowns are most commonly used as the complete coverage restorations in clinical daily use. Disadvantages of conventional hand-made wax-patterns introduce some alternative ways by means of CAD/CAM technologies. This study compares the marginal and internal fit of copings cast from CAD/CAM and conventional fabricated wax-patterns. Twenty-four standardized brass dies were prepared and randomly divided into 2 groups according to the wax-patterns fabrication method (CAD/CAM technique and conventional method) (n=12). All the wax-patterns were fabricated in a standard fashion by means of contour, thickness and internal relief (M1-M12: representative of CAD/CAM group, C1-C12: representative of conventional group). CAD/CAM milling machine (Cori TEC 340i; imes-icore GmbH, Eiterfeld, Germany) was used to fabricate the CAD/CAM group wax-patterns. The copings cast from 24 wax-patterns were cemented to the corresponding dies. For all the coping-die assemblies cross-sectional technique was used to evaluate the marginal and internal fit at 15 points. The Student's t- test was used for statistical analysis (α=0.05). The overall mean (SD) for absolute marginal discrepancy (AMD) was 254.46 (25.10) um for CAD/CAM group and 88.08(10.67) um for conventional group (control). The overall mean of internal gap total (IGT) was 110.77(5.92) um for CAD/CAM group and 76.90 (10.17) um for conventional group. The Student's t-test revealed significant differences between 2 groups. Marginal and internal gaps were found to be significantly higher at all measured areas in CAD/CAM group than conventional group (p< 0.001). Within limitations of this study, conventional method of wax-pattern fabrication produced copings with significantly better marginal and internal fit than CAD/CAM (machine-milled) technique. All the factors for 2 groups were standardized except wax pattern fabrication technique, therefore, only the conventional group results in copings with clinically acceptable margins of less than 120um.


A 'High Risk' Lifestyle Pattern Is Associated with Metabolic Syndrome among Qatari Women of Reproductive Age: A Cross-Sectional National Study.
This study investigated the effect of lifestyle patterns, as a combination of diet, physical activity and smoking, on Metabolic Syndrome (MetS) among Qatari women of childbearing age (n = 418), a population group particularly vulnerable to the health sequela of this syndrome. Using data from the National WHO STEPwise survey conducted in Qatar in 2012, Principal Component Factor Analysis was performed to derive lifestyle patterns with survey variables related to the frequency of consumption of 13 foods/food groups, physical activity levels, and smoking status. MetS was diagnosed using ATPIII criteria. Three lifestyle patterns were identified: 'High Risk' pattern, characterized by intakes of fast foods, sweets and sugar sweetened beverages, in addition to lower levels of physical activity and higher smoking prevalence; 'Prudent' pattern, driven mainly by higher intakes of fruits, vegetables, fish, and whole grains; and 'Traditional' pattern which included beans, meat, dairy products, and a low prevalence of smoking. Among these three lifestyle patterns, only the 'High Risk' was associated with MetS, whereby subjects belonging to the third tertile of this pattern's score had 2.5 times the odds of MetS compared to those belonging to the first tertile. The findings of this study demonstrated the synergy among high risk behaviors among Qatari women in increasing the odds of MetS; the latter being a major risk factor for cardiovascular diseases.


The effects of endurance exercise training on ambulatory blood pressure in normotensive older adults.
This study investigated the effects of 16-weeks of endurance exercise training (EET) on ambulatory blood pressure in older adults. Twenty-one men and women, 68.5 +/- 4.7 (mean +/- SD) years of age were randomly assigned to an exercise group (EG, n = 11) or to a control group (CG, n = 10). Subjects were normotensive (mean resting BP 132.0 +/- 8.6/80.1 +/- 6.6 mm Hg), free from overt cardiovascular or renal diseases, and were taking no vasoactive or diuretic medications. Maximal oxygen uptake (VO2max), body composition, resting BP, and 24-hr ambulatory systolic (ASBP) and diastolic (ADBP) blood pressures were measured in all subjects before and after the study period. The EG completed 16 weeks (3, 1-hour bouts/wk) of EET, progressing in intensity from 50% to 85% of maximal workload. The CG did not exercise. In the EG, although body composition and resting BP did not change (p > 0.05), VO2max increased by 14% (p = 0.001), mean 24-hr ASBP decreased 7.9 mm Hg (p = 0.0001), and mean 24-hr ADBP decreased 3.6 mm Hg (p = 0.002). In the CG, there were no significant changes in these variables (p > 0.05). These data suggest that EET can improve both aerobic fitness and "real-life" blood pressures in healthy older adults and may help inhibit increases in blood pressure associated with normal aging.


Basal Levels of CD18 Antigen Presenting Cells in Cow Milk Associate with Copy Number Variation of Fc Gamma Receptors.
Differentiation of cells by flow cytometry provides informative somatic cell counts (SCCs) that allow analyzing leukocyte population patterns in udder infections of different etiologies. Postulating that this approach also enhances the statistical power to detect genetic variants linked to cell levels in milk of healthy mammary glands, we used monoclonal antibodies anti-CD18, anti-CD4, anti--CD14, and anti-PMN to count cells presenting these surface antigens, and performed a genome-wide association study of these counts in 125 Israeli Holsteins genotyped using SNP BeadChips. We identified an informative haplotype of 15 SNPs in the centromeric end of BTA3 that was strongly associated with CD18 cells (p < 2.3 × 10-9). Within this region, examination of the network of genes interacting with ITGB2 (CD18) indicated an Fc-γ-receptor gene cluster, including FCGR2A (CD32). Sanger-sequence analysis of FCGR2s-linked exon 3 variation to CD18 counts. Meta-analysis of RNA-Seq data revealed a significant negative correlation (R = -0.51) between expression of CD32 and CD18 in milk. Assembly of DNA-Seq reads uncovered FCGR copy-number variation and a variant, designated V7, was abundant in dairy cattle, probably reflecting adaptation to selection pressure for low SCC in Holstein milk.


Cassava starch maltodextrinization/monomerization through thermopressurized aqueous phosphoric acid hydrolysis.
Kinetic conditions were established for the depolymerization of cassava starch for the production of maltodextrins and glucose syrups. Thin-layer chromatography and high-performance liquid chromatography analyses corroborated that the proper H3PO4 strength and thermopressurization range (e.g., 142-170 degrees C; 2.8-6.8 atm) can be successfully explored for such hydrolytic purposes of native starch granules. Because phosphoric acid can be advantageously maintained in the hydrolysate and generates, after controlled neutralization with ammonia, the strategic nutrient triplet for industrial fermentations (C, P, N), this pretreatment strategy can be easily recognized as a recommended technology for hydrolysis and upgrading of starch and other plant polysaccharides. Compared to the classic catalysts, the mandatory desalting step (chloride removal by expensive anion-exchange resin or sulfate precipitation as the calcium-insoluble salt) can be avoided. Furthermore, properly diluted phosphoric acid is well known as an allowable additive in several popular soft drinks such as colas since its acidic feeling in the mouth is compatible and synergistic with both natural and artificial sweeteners. Glycosyrups from phosphorolyzed cassava starch have also been upgraded to high-value single-cell protein such as the pigmented yeast biomass of Xanthophyllomyces dendrorhous (Phaffia rhodozyma), whose astaxanthin (diketo-dihydroxy-beta-carotene) content may reach 0.5-1.0 mg/g of dry yeast cell. This can be used as an ideal complement for animal feeding as well as a natural staining for both fish farming (meat) and poultry (eggs).


Vaccination of lambs against Taenia ovis infection using antigens collected during in vitro cultivation of larvae: passive protection via colostrum from vaccinated ewes and the duration of immunity from a single vaccination.
Fifty Merino-cross ewes were vaccinated approximately four weeks before parturition with antigens collected during in vitro cultivation of Taenia ovis larvae. A further 50 pregnant ewes were sham-vaccinated at the same time. When the first 20 lambs from each group of ewes were one to two weeks old they were placed, with the ewes, on an experimental paddock heavily contaminated with T ovis eggs. After six weeks the lambs were killed and their total carcase musculature and hearts examined for cysticerci. The results showed that the ewes vaccinated in late pregnancy had conferred a very high degree of transcolostral immunity upon their lambs against the T ovis challenge infection. Eighty T ovis-free Merino-cross weaner lambs, four months old, were divided into two groups of 40. One group was vaccinated with T ovis culture antigens and the other group was sham-vaccinated. At intervals of one, four, eight and 12 months after vaccination 10 lambs from each group were allowed to graze on the plot contaminated with T ovis eggs. After six weeks the lambs were killed and examined for cysticerci of T ovis. The results indicated that the single vaccination had stimulated a high level of immunity which persisted for at least 12 months.


Ultrasound-guided intrauterine device insertion: a step closer to painless insertion: a randomized control trial.
To reduce the pain and duration of the intrauterine device (IUD) insertion procedure through minimizing instrumentation and using trans-abdominal sonography (TAS). This randomized control trial was conducted in a university hospital and included 102 eligible females, fulfilling the inclusion criteria. They were randomly assigned into two groups via 1:1 computer-based randomization program; the trans-abdominal guided IUD insertion group (n = 51), and the traditional IUD insertion group (n = 51). The main outcomes were the pain experienced during the procedure as scored by the visual analogue score and the duration of the procedure. The trans-abdominal guided IUD insertion was found to be statistically superior to the traditional technique for IUD insertion regarding the pain scores (according to the Visual Analogue Scale, from 0 to 10) recorded by the candidates (2.4 ± 2.1 vs. 5.0 ± 1.7, p < .001) as well as the time (in seconds) taken for IUD insertion procedure (32.2 ± 14.8 vs. 77.7 ± 30.6, p < .001). Due to the decrease in pain and time taken for IUD insertion, the trans-abdominal guided technique can be used as a modified technique for IUD insertion. ClinicalTrials.gov Identifier: NCT02582268.


Enhanced expression of a cloned and sequenced Ciona intestinalis TNFalpha-like (CiTNF alpha) gene during the LPS-induced inflammatory response.
A tumor necrosis factor-alpha (TNFalpha)-like gene from Ciona intestinalis (CiTNF alpha-like) body wall challenged with bacterial lipopolysaccharide (LPS) was cloned and sequenced 4 h after LPS inoculation. An open reading frame of 936 bp encoding a propeptide of 312 amino acids (35.4 kDa) displaying a transmembrane domain from positions 7 to 29, a TACE cleavage site, and a mature peptide domain of 185 amino acids (20.9 kDa), was determined with a predicted isoelectric point of 9.4. The phylogenetic tree based on deduced amino acid sequences of invertebrate TNF-like protein and vertebrate TNFs supported the divergence between the ascidian and vertebrate TNF families, whereas D. melanogaster Eiger A and B TNF-like sequences were distinctly separated from the chordate TNFs. Thus, the ascidian TNFalpha-like cytokine was upregulated by in vivo LPS challenge supporting its pro-inflammatory role. In the pharynx, increased expression levels were found following analysis by real-time polymerase chain reaction, whereas in situ hybridization assay showed positive hemocytes both in the tissue and in circulating hemocytes. Finally, Western blot with monoclonal antibodies disclosed human TNFalpha epitopes in a 15-kDa protein component of the hemolymph serum and in a 43-kDa protein contained in the hemocyte lysate supernatant prepared in the presence of detergents. Both soluble and hemocyte-bound CiTNF alpha-like protein therefore appeared to be modulated by the LPS challenge.


Pushing the envelope: The who, what, when, and why of critical consciousness.
Deep-seated structural racism in the U.S. has been thrown into bold relief by the racially disproportionate impacts of COVID-19 and a series of highly visible police murders of Black Americans. Longstanding and intergenerational economic inequalities have been laid bare by the ensuing economic recession. This special issue's focus on how people critique, challenge, negotiate and change inequities is therefore particularly (and, unfortunately) relevant and timely. These three papers approach critical consciousness from three distinct angles. In this commentary, I will offer several points of praise for these three papers, along with a few suggestions on ways that the authors' lines of thinking could be extended or more nuanced. I will identify a few themes that cut across these three papers: (1) the importance of focusing on critical action, (2) how these papers advance our thinking on how, when, and for whom CC develops, with specific attention paid to the social identities, life phases, and events that impact CC, and (3) a deepening of our understanding of the antecedents and consequences of CC. In reviewing these three papers, I consider how each of them adds to the collective conversation about the ways that we might recognize, challenge, and work to change marginalizing systems and transform inequity to create a more just world.


Mercury capture into biogenic amorphous selenium nanospheres produced by mercury resistant Shewanella putrefaciens 200.
Shewanella putrefaciens 200, resistant to high concentration of Hg(II), was selected for co-removal of mercury and selenium from aqueous medium. Biogenic Hg(0) reduced from Hg(II) by S. putrefaciens 200 was captured into extracellular amorphous selenium nanospheres, resulting in the formation of stable HgSe nanoparticles. This bacterial reduction could be a new strategy for mercury removal from aquatic environments without secondary pollution of mercury methylation or Hg(0) volatilization.


Effectiveness and mode of action of whitening dentifrices on enamel extrinsic stains.
This study was conducted in order to investigate the mode of action and the whitening effect of whitening dentifrices. Two hundred fifty-six bovine enamel specimens (10 × 10 mm(2)) were prepared, partially stained, and assigned into eight groups (n = 32): six whitening dentifrices, one nonwhitening and deionized water (negative control), and further divided in two subgroups (n = 16), according to the test model: chemical (dentifrice slurry treatment only) or chemo-mechanical (slurry + toothbrushing). Specimens were treated with dentifrice slurries 2 ×/day for 1 min and toothbrushed or not, according to each model. In between dentifrice treatments, specimens were artificially stained for 5 h. This protocol was repeated for 5 days and enamel color changes (∆E) were measured after each day (days 1-5). The abrasive level of the dentifrices was determined following the ISO11609 guidelines. In the chemo-mechanical model, the whitening action of all dentifrices was observed after day 1, being higher than the negative control group (p < 0.05). In days 2-5, nonsignificant changes in color were observed for all groups (p > 0.05). Differences on ∆E among dentifrices were observed, and they seemed to correlate well with their abrasive level (r(2) = 0.80). In the chemical model, no significant differences were observed among groups (p > 0.05), with ∆E remaining constant throughout the study. Higher ∆E values were observed in the chemo-mechanical model compared to the chemical (p < 0.05). All tested dentifrices were effective in whitening stained enamel and their mode of action showed to be mainly mechanical (toothbrushing abrasion). The abrasive level of dentifrices seems to determine its whitening effectiveness.


Cytofluorometric DNA base determination for the investigation of heterochromatin and heterochromatin amplification.
The measurement of chromomycin A3/DAPI fluorescence ratios is shown to allow base content determinations in eu- and heterochromatic regions of interphase cell nuclei. The base content values obtained in chromocenters and euchromatin of Scilla sibirica agree with those measured earlier [12] on the band and non-band areas of the chromosomes of this species. In Sinapis alba three different heterochromatin types, with regard to base content, can be discerned. The heterochromatin amplification observed in the polyploid nuclei of Sinapis roots and hypocotyl involves either all three heterochromatin types, with little resulting change of the total nuclear base content, or only one or the other of them, with a measurable shift of the base content.


Characterization of the genomic RNA from a Rous sarcoma virus mutant temperature sensitive for cell transformation.
We have found that the LA23 t/s mutant of Rous sarcoma virus (phenotype Prague B), even when passaged repeatedly at high multiplicity of infection, does not give rise to transformation defective deletion mutants comparable to those derived from RSV. In view of this fact and of the high rate of production of this mutant at 41 degrees C, we have undertaken a detailed analysis of the genome of this virus by ordering all large T1 oligonucleotides and by determining their nucleotide sequences. The results indicate a high degree of mutation in the onc gene as compared to that of Pr-A or Pr-B.


The heterocyclic ruthenium(III) complex KP1019 (FFC14A) causes DNA damage and oxidative stress in colorectal tumor cells.
The Ru(III) complex salt KP1019 induced formation of H2O2 in colorectal tumor cells in a dose-dependent way. It also caused DNA-strand breaks if only weakly doubling tail length to 55.87+/-3.97 microm. Both effects were prevented by 5mM N-acetylcysteine (NAC) which also reduced cytotoxicity (IC(50) 55 vs 30 microM without NAC). Induction of apoptosis was shown by loss of mitochondrial membrane potential in 63.4+/-2.1% of the population and by caspase-dependent cleavage of poly-(ADP-ribose)-polymerase (PARP). Both effects were inhibited by NAC which reduced the population with depolarized mitochondrial membranes to 24.1+/-1.2% and prevented PARP-cleavage indicating a central role oxidative stress in KP1019-induced apoptosis.


A CpG oligonucleotide can protect mice from a low aerosol challenge dose of Burkholderia mallei.
Treatment with an oligodeoxynucleotide (ODN) containing CPG motifs (CpG ODN 7909) was found to protect BALB/c mice from lung infection or death after aerosol challenge with Burkholderia mallei. Protection was associated with enhanced levels of gamma interferon (IFN-gamma)-inducible protein 10, interleukin-12 (IL-12), IFN-gamma, and IL-6. Preexposure therapy with CpG ODNs may protect victims of a biological attack from glanders.


Herbivory and abiotic factors affect population dynamics of Arabidopsis thaliana in a sand dune area.
Population dynamics of the annual plant Arabidopsis thaliana (L.) Heynh. were studied in a natural habitat of this species on the coastal dunes of the Netherlands. The main objective was to elucidate factors controlling population dynamics and the relative importance of factors affecting final population density. Permanent plots were established and plants were mapped to obtain data on survival and reproductive performance of each individual, with special attention to herbivore damage. In experimental plots we studied how watering, addition of nutrients, artificial disturbance, and natural herbivores affected survival and growth. Mortality was low during autumn and early winter and high at the time of stem elongation, between February and April. A key factor analysis showed a high correlation between mortality from February to April and total mortality. The specialist weevils Ceutorhyncus atomus and C. contractus (Curculionidae) were identified as the major insect herbivores on A. thaliana, reducing seed production by more than 40 %. These herbivores acted in a plant size-dependent manner, attacking a greater fraction of the fruits on large plants. While mortality rates were not affected by density, fecundity decreased with density, although the effect was small. Adding water reduced mortality in rosette and flowering plant stages. Soil disturbance did not increase seed germination, but did have a significant positive effect on survival of rosette and flowering plants. Seed production of A. thaliana populations varied greatly between years, leading to population fluctuations, with a small role for density-dependent fecundity and plant size-dependent herbivory.


A bottom-up clustering approach to identify bus driving patterns and to develop bus driving cycles for Hong Kong.
Bus transport has been an important mode taking up a significant share of urban travel demand and thus the corresponding impacts on the environment are of great concerns. Use of driving cycles to evaluate the environmental impacts of buses has attracted much attention in recent years worldwide. The franchised bus service is currently playing important roles in the public transport system in Hong Kong; however, there is no driving cycle developed specifically for them. A set of bus driving cycle was therefore developed using a bottom-up approach where driving data on the bus network with mixed characteristics were collected. Using the Ward's method for clustering, the collected data were then categorized into three clusters representing distinct franchised bus route patterns in Hong Kong. Driving cycles were then developed for each route pattern including (i) congested urban routes with closely spaced bus stops and traffic junctions; (ii) inter-district routes containing a number of stop-and-go activities and a significant portion of smoother high speed driving; and (iii) early morning express routes and mid-night routes connecting remote residential areas and urban areas. These cycles highlighted the unique low-speed and aggressive driving characteristics of bus transport in Hong Kong with frequent stop-and-go activities. The findings from this study would definitely be helpful in assessing the exhaust emissions, fuel consumptions as well as energy consumptions of bus transport. The bottom-up clustering approach adopted in this study would also be useful in identifying specific driving patterns based on vehicle speed trip data with mixed driving characteristics. It is believed that this approach is especially suitable for assessing fixed route public transport modes with mixed driving characteristics.


Nucleotide insertion and bypass synthesis of pyrene- and BODIPY-modified oligonucleotides by DNA polymerases.
The chromophores pyrene and bordipyrromethenylbenzene directly linked to the 5-position of uridine are tolerated and recognized as thymine derivatives by DNA polymerases in primer extension experiments.


Comparison of fluorescent labels for oligosaccharides and introduction of a new postlabeling purification method.
Labeling of oligosaccharides with fluorescent dyes is the prerequisite for their sensitive analysis by high-performance liquid chromatography (HPLC). In this work, we present a fast new postlabeling cleanup procedure that requires no device other than the reaction vial itself. The procedure can be applied to essentially all labeling reagents. We also compare the performance of 15 different labels for N-glycan analysis in various analytical procedures. We took special care to prevent obscuring influences from incomplete derivatization and signal quenching by impurities. Procainamide emerged as more sensitive than anthranilic acid for normal-phase HPLC, but its chromatographic performance was not convincing. 2-aminopyridine was the label with the lowest retention on reversed-phase and graphitic carbon columns and, thus, appears to be most suitable for glycan fractionation by multidimensional HPLC. Most glycan derivatives performed better than native sugars in matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) and electrospray ionization-MS (ESI-MS), but the gain was small and hardly sufficient to compensate for sample loss during preparation.


Bifidobacterium breve Probiotic Compared to Lactobacillus casei Causes a Better Reduction in Demyelination and Oxidative Stress in Cuprizone-Induced Demyelination Model of Rat.
Despite the anatomical separation, strong evidence suggested a bidirectional association between gut microbiota and central nervous system. Cross-talk between gut microbiota and brain has an important role in the pathophysiology of neurodegenerative disorders and regenerative processes. However, choosing the appropriate probiotics and combination therapy of probiotics to provide a synergistic effect is very crucial. In the present study, we investigated the effect of Lactobacillus casei (L. casei) and Bifidobacterium breve (B. breve) on alternation performance, oxidant/antioxidant biomarkers, the extent of demyelination, and the expression level of HO-1, Nrf-2, Olig2, MBP, PDGFRα, and BDNF in cuprizone (CPZ)-induced demyelination model of rat corpus callosum. In order to induce this model, rats received oral administration of CPZ 0.6% w/w in corn oil for 28 days. Then, L. casei, B. breve, or their combinations were orally administrated for 28 days. Y maze test was performed to investigate the alternation performance. Oxidant/antioxidant biomarkers were determined by colorimetric methods. Extent of demyelination was investigated using FluoroMyelin staining. The genes' expression levels of antioxidant and myelin lineage cells were assessed by quantitative real time PCR. The results showed the probiotics supplementation significantly improve the alternation performance and antioxidant capacity in demyelinated corpus callosum. Interestingly, B. breve supplementation alleviated demyelination and oxidative stress levels more than the administration of L. casei alone or the combination of two probiotics. These observations suggest that B. breve could provide a supplementary strategy for the treatment of multiple sclerosis by increasing antioxidant capacity and remyelination.


Early identification of individuals at high risk for cerebral infarction after aneurysmal subarachnoid hemorrhage: the BEHAVIOR score.
Cerebral infarction (CI) is a crucial complication of aneurysmal subarachnoid hemorrhage (SAH) associated with poor clinical outcome. We aimed at developing an early risk score for CI based on clinical characteristics available at the onset of SAH. Out of a database containing 632 consecutive patients with SAH admitted to our institution from January 2005 to December 2012, computed tomography (CT) scans up to day 42 after ictus were evaluated for CIs. Different parameters from admission up to aneurysm treatment were collected with subsequent construction of a risk score. Seven clinical characteristics were independently associated with CI and included in the Risk score (BEHAVIOR Score, 0 to 11 points): Blood on CT scan according to Fisher grade ⩾3 (1 point), Elderly patients (age ⩾55 years, 1 point), Hunt&Hess grade ⩾4 (1 point), Acute hydrocephalus requiring external liquor drainage (1 point), Vasospasm on initial angiogram (3 points), Intracranial pressure elevation >20 mm Hg (3 points), and treatment of multiple aneurysms ('Overtreatment', 1 point). The BEHAVIOR score showed high diagnostic accuracy with respect to the absolute risk for CI (area under curve=0.806, P<0.0001) and prediction of poor clinical outcome at discharge (P<0.0001) and after 6 months (P=0.0002). Further validation in other SAH cohorts is recommended.


Eleutheroside E from pre-treatment of Acanthopanax senticosus (Rupr.etMaxim.) Harms ameliorates high-altitude-induced heart injury by regulating NLRP3 inflammasome-mediated pyroptosis via NLRP3/caspase-1 pathway.
Eleutheroside E, a major natural bioactive compound in Acanthopanax senticosus (Rupr.etMaxim.) Harms, possesses anti-oxidative, anti-fatigue, anti-inflammatory, anti-bacterial and immunoregulatory effects. High-altitude hypobaric hypoxia affects blood flow and oxygen utilisation, resulting in severe heart injury that cannot be reversed, thereby eventually causing or exacerbating high-altitude heart disease and heart failure. The purpose of this study was to determine the cardioprotective effects of eleutheroside E against high-altitude-induced heart injury (HAHI), and to study the mechanisms by which this happens. A hypobaric hypoxia chamber was used in the study to simulate hypobaric hypoxia at the high altitude of 6000 m. 42 male rats were randomly assigned to 6 equal groups and pre-treated with saline, eleutheroside E 100 mg/kg, eleutheroside E 50 mg/kg, or nigericin 4 mg/kg. Eleutheroside E exhibited significant dose-dependent effects on a rat model of HAHI by suppressing inflammation and pyroptosis. Eleutheroside E downregulated the expressions of brain natriuretic peptide (BNP), creatine kinase isoenzymes (CK-MB) and lactic dehydrogenase (LDH). Moreover, The ECG also showed eleutheroside E improved the changes in QT interval, corrected QT interval, QRS interval and heart rate. Eleutheroside E remarkably suppressed the expressions of NLRP3/caspase-1-related proteins and pro-inflammatory factors in heart tissue of the model rats. Nigericin, known as an agonist of NLRP3 inflammasome-mediated pyroptosis, reversed the effects of eleutheroside E. Eleutheroside E prevented HAHI and inhibited inflammation and pyroptosis via the NLRP3/caspase-1 signalling pathway. Taken together, eleutheroside E is a prospective, effective, safe and inexpensive agent that can be used to treat HAHI.


General method for the analysis of pharmaceutical dosage forms by high-performance liquid chromatography.
A reliable and simple method for the routine analysis of pharmaceutical dosage forms by high-performance liquid chromatography using a C18 Bondapak reversed-phase column with a binary solvent system consisting of acetonitrile and 0.05 M potassium dihydrogen phosphate has been developed. Standardised extraction procedures for drugs in various dosage forms have been developed and successfully applied to a wide range of current pharmaceutical formulations.


The role of estrogen receptor subtypes on hepatic neutrophil accumulation following trauma-hemorrhage: direct modulation of CINC-1 production by Kupffer cells.
Although 17beta-estradiol (E2) administration following trauma-hemorrhage (T-H) reduces liver injury by decreasing neutrophil accumulation via estrogen receptor (ER)-alpha, it remains unclear whether cytokine-induced neutrophil chemoattractant (CINC)-1 production by Kupffer cells (KC) is directly modulated by ER-alpha under such condition. Male rats underwent laparotomy and hemorrhagic shock (40 mmHg for 90 min), followed by resuscitation with four times the shed blood volume in the form of Ringer's lactate. ER-alpha agonist propyl pyrazole triol (PPT; 5 microg/kg), ER-beta agonist diarylpropionitrile (DPN; 5 microg/kg), E2 (50 microg/kg), or vehicle (10% DMSO) was administered subcutaneously during resuscitation; rats were sacrificed 24h thereafter. KC were isolated and cultured with ER agonists to examine if they directly affect CINC-1 production. T-H increased plasma alanine aminotransferase (ALT; hepatic injury) and hepatic myeloperoxidase (MPO) activity. E2, PPT and DPN administration reduced increased ALT; however, PPT was more effective than DPN. PPT and E2, but not DPN significantly attenuated increased hepatic MPO activity and CINC-1 levels. PPT addition in vitro (10(-7) and 10(-6)M) significantly reduced KC CINC-1 production. In summary, the salutary effects of E2 against hepatic injury are mediated predominantly via ER-alpha which directly modulates KC CINC-1 production and hepatic neutrophil accumulation following T-H.


Cyclooxygenase 2 expression in chronic pancreatitis: correlation with stage of the disease and diabetes mellitus.
Fibrotic replacement of the exocrine pancreatic parenchyma and infiltration of inflammatory cells are the main characteristics of chronic pancreatitis (CP). Inflammation involves prostaglandin production in numerous inflammatory and noninflammatory cells, and cyclooxygenase 2 (COX-2) is the dominant regulator of prostaglandin synthesis. In the present study, we analyzed the expression of COX-2, the key enzyme for prostaglandin synthesis in pancreatic tissues, and evaluated its relation to exocrine and endocrine tissue alterations in CP. Pancreatic tissue specimens from 27 patients undergoing pancreatic head resection for CP were included in the study. Pancreatic tissues from 14 organ donors served as controls. The tissue specimens were analyzed histopathologically and for COX-2 immunoreactivity. In normal pancreatic tissue samples, COX-2 immunoreactivity was restricted to islet cells. In contrast, in early-stage CP, islets as well as ductal cells showed intense COX-2 immunoreactivity. In advanced-stage CP, ductal cells were still strongly positive for COX-2, yet islets displayed a variable COX-2 staining pattern which was associated with the distribution of insulin-positive cells and with the clinical diabetes mellitus status of the patient. Thus, patients with normal or latent diabetes mellitus status showed COX-2 immunoreactivity, whereas in diabetic patients the COX-2 immunoreactivity was decreased or absent in pancreatic islets. The presence of COX-2 in ductal cells of early and advanced CP, the relationship between COX-2 and insulin expression in the islets, and the diabetes mellitus status of CP patients suggest that this enzyme plays a role in the pathogenesis of exocrine and endocrine damage in CP.


Gastrointestinal health care resource utilization with chronic use of COX-2-specific inhibitors versus traditional NSAIDs.
Cyclooxygenase 2 (COX-2)-specific inhibitors (coxibs) decrease gastrointestinal (GI) events in controlled trials, but results in clinical practice are unknown. We assessed GI-related resource use and costs in patients switching from chronic nonsteroidal anti-inflammatory drug (NSAID) therapy to chronic coxib therapy and in patients starting chronic NSAID therapy vs. chronic coxib therapy in a U.S. administrative claims database of >8 million lives. "Switchers" (n = 2246) were assessed in the 12-month periods before and after switching from chronic NSAID therapy to coxib therapy. "New NSAID" (n = 25,989) and "new coxib" (n = 2125) groups were assessed for the 12-month periods before and after the initial prescription. Proportions of patients with GI resource use (odds ratio [OR] adjusted for relevant covariates) and costs were compared. The adjusted OR for any GI resource use (coxib vs. NSAID period) among switchers was 0.86 (0.74-0.99). The decrease was due to less GI cotherapy (OR = 0.82 [0.69-0.97]). Costs were not significantly lower after switching to coxibs (mean difference, -$19; 95% CI: -$139, $55), although after adding NSAID/coxib costs, the total cost in the coxib period was significantly higher (mean increase, $377; $271, $488). Adjusted OR for GI resource use for new-coxib vs. new-NSAID was 1.04 (0.92-1.16), but GI costs were significantly lower in new-NSAID patients. Patients switching from chronic NSAID therapy to chronic coxib therapy had a slight decrease in the proportion using GI-related resources but not in GI costs. When NSAID/coxib drug costs were included, costs were significantly less with NSAIDs than with coxibs. The potential GI-related cost savings suggested in coxib clinical trials may not be fully realized in "real-world" settings.


Alien or Native? How to Distinguish Feces of Fallow and Roe Deer Using Central Poland as a Case Study.
The method of pellet group count is commonly used for estimating population trends of ungulates; however, in the case of species of similar body size, the misidentification rate can be high. Our aim was to find a metrical threshold between pellet groups of roe deer (native species) and fallow deer (alien species) to be applied during fieldwork. The study was conducted in spring 2020 and 2021 in central Poland (lowlands) in areas were only roe or fallow deer occurred. We measured the number of feces in the group, the length and width of five randomly selected feces from each pellet group and the length/width ratio. Roe deer pellets were shorter, narrower and less elongated than those of fallow deer; yet, length was found to be the best discriminant. The most accurate threshold was 1.2 cm, i.e., 12-15% of pellets were over/below this value. The mean number of pellets in a group was lower for roe deer (39.6, SE = 1.6) than for fallow deer (64.5, SE = 1.5). A value of 50-52 pellets best differentiated between the two species. To conclude, combining these two measurements could be an objective method to distinguish between pellet groups of the two species.


Posterior polymorphous dystrophy of the cornea. An ultrastructural study.
A corneal button excised from a 2-month-old infant with congenital posterior polymorphous dystrophy of the cornea, a rare disease affecting Descemet's membrane and endothelium, was examined by electron microscopy. We observed irregularly arranged, sometimes multilayered cells with marked epithelial features, lining the posterior surface of the cornea in place of the endothelium, and Descemet's membrane with focal alterations sometimes involving all of its layers. We interpreted these abnormal cells as epithelial-like cells. As these findings were in a very young patient, which is unusual, we concluded that the onset of the disease may take place in the early period of intrauterine life, corresponding to the beginning of Descemet's membrane production.


Sounding It Out: Auditory Stimulation and Overnight Memory Processing.
Auditory stimulation is a technique that can enhance neural oscillations linked to overnight memory consolidation. In this review, we evaluate the impacts of auditory stimulation on the neural oscillations of sleep and associated memory processes in a variety of populations. Cortical EEG recordings of slow-wave sleep (SWS) are characterised by two cardinal oscillations: slow oscillations (SOs) and sleep spindles. Auditory stimulation delivered in SWS enhances SOs and phase-coupled spindle activity in healthy children and adults, children with ADHD, adults with mild cognitive impairment and patients with major depression. Under certain conditions, auditory stimulation bolsters the benefits of SWS for memory consolidation, although further work is required to fully understand the factors affecting stimulation-related memory gains. Recent work has turned to rapid eye movement (REM) sleep, demonstrating that auditory stimulation can be used to manipulate REM sleep theta oscillations. Auditory stimulation enhances oscillations linked to overnight memory processing and shows promise as a technique for enhancing the memory benefits of sleep.


Concentrations of drugs determined in blood samples collected from suspected drugged drivers in England and Wales.
This communication reports the blood concentrations of alcohol and drugs from 376 cases of alleged driving under the influence of drugs analysed at the Forensic Science Service Chorley and London laboratories between February 2010 and March 2011. The samples were analysed for alcohol, amphetamine, benzodiazepines, cocaine, MDMA, opiates, γ-hydroxybutyrate (GHB), ketamine, methadone and methylmethcathinone (the 4-isomer of which is known as mephedrone). The results were interpreted with respect to the number and type of drugs of abuse detected and the concentrations measured. Alcohol was quantified in 113 cases (30%), and of these a level in excess of the prescribed UK limit for driving of 80 mg% was present in 90 cases. In 80 cases, only the concentration of alcohol was measured, the concentrations of both drugs and alcohol were measured in 33 cases. In the remaining 263 cases, only the concentrations of relevant drugs of abuse were measured. The most common drug of abuse quantified was cocaine which was detected in 92 cases, either as the active drug or as its major metabolite benzoylecgonine, followed by diazepam which was quantified in 76 cases. Concentrations of some new drugs, and drugs rarely reported in driving under the influence cases are also presented.


Cross-calibration of Lunar DPX-IQ and DPX dual-energy x-ray densitometers for bone mineral measurements in women: effect of body anthropometry.
When dual-energy X-ray absorptiometry (DXA) instruments are replaced, it is essential to determine if systematic differences in measurements occur. As a part of the Kuopio Osteoporosis Risk Factor and Prevention study (N=14,220), a group of women, aged 36 to 69 yr underwent anteroposterior lumbar spine L2 to L4 (n=89) and proximal femur scans (n=88) by the Lunar DPX and DPX-IQ, respectively, during the same visit. A high linear association (r from 0.944 to 0.989, p<0.001) between the two scanners was established for lumbar spine and proximal femur bone mineral density (BMD). The average DPX values for BMD were 1.1% and 2.0% higher than those of DPX-IQ for the lumbar spine (p<0.001) and Ward's triangle (p=0.001), respectively. Femoral neck BMD values by the DPX were 1.4% lower (p<0.001) compared to DPX-IQ. The difference between trochanter BMD results (0.1%) was not significant (p=0.809). In the femoral neck and trochanter, but not in the lumbar spine or Ward's triangle, the differences in BMD values of the two machines were found to depend on body mass index. After linear formulas based on simple and multivariate linear regression analyses were calculated, the differences were negligible, enabling objective comparison of longitudinal measurements.


Giant right atrial aneurysm associated with persistent left cranial vena cava in a cat.
A 10-month-old female spayed Scottish Fold was referred to cardiology for incidental radiographic cardiomegaly. Echocardiography was suspicious for a right atrial or right auricular aneurysm. The differential diagnosis also included peritoneal-pericardial diaphragmatic hernia, mass lesion (cyst, granuloma, or neoplasia), or cardiac malformation. A giant right atrial aneurysm associated with a persistent left cranial vena cava was subsequently confirmed with computed tomography.


Clinical and pathologic factors of prognostic significance in penile squamous cell carcinoma in a North American population.
To analyze, in a clinicopathologic correlation study, a small population of primarily white men with invasive squamous cell carcinoma of the penis for potential prognostic predictors. Penile squamous cell carcinoma is an uncommon cancer in North America. It has a wide spectrum of clinical behavior and an understudied pathogenesis. The data from 43 patients with invasive squamous cell carcinoma of the penis were studied retrospectively. Extensive chart reviews were conducted, glass slides were reviewed, and tissue microarrays were constructed for analysis of immunohistochemical stains p16(INK4a), p53, and Ki-67. Univariate and multivariate logistic regression analyses were performed to elucidate any clinical or pathologic factors that would predict overall survival. The mean age at diagnosis was 63 years. Most cases (63%) were invasive squamous cell carcinoma, not otherwise specified, and presented as pathologic stage T1 or T2 tumors. Of the 43 patients, 23% died of their disease; 53% of the cases stained for p16(INK4a). Higher pathologic tumor stage and a lack of p16(INK4a) staining were independent predictors of worse overall survival (P = .014) and cancer-specific survival (P = .010). Our results have shown that 53% of the invasive penile squamous cell carcinoma cases in this population were associated with human papillomavirus, using p16(INK4a) as a surrogate marker of human papillomavirus infection. These patients had a statistically significant survival advantage, independent of other prognostic factors.


Autophagy and the invisible line between life and death.
For a considerable time cell death has been considered to represent mutually exclusive states with cell death modalities that are governed by their inherent and unique mode of action involving specific molecular entities and have therefore been studied primarily in isolation. It is now, however, becoming increasingly clear that these modalities are regulated by similar pathways and share a number of initiator and effector molecules that control both cell death as well as cell survival mechanisms, demanding a newly aligned and integrative approach of cell death assessment. Frequently cell death is triggered through a dual action that incorporates signaling events associated with more than one death modality. Apoptosis and necrosis regularly co-operate in a tightly balanced interplay that involves autophagy to serve context dependently either as a pro-survival or a pro-death mechanism. In this review we will assess current cell death modalities and their molecular overlap with the goal of clarifying the controversial role of autophagy in the cell death response. By dissecting the key molecular pathways and their positioning within a network of regulatory signalling hubs and checkpoints we discuss a distinct approach that integrates autophagy with a resultant cell death manifestation. In doing so, former classifications of cell death modalities fade and reveal the intricate molecular proportions and complexities of the cell death response that may contribute towards an enhanced means of cell death control.


Trends and outcomes of children, adolescents, and adults hospitalized with inherited metabolic disorders: A population-based cohort study.
Inherited metabolic disorders (IMDs) comprise a heterogeneous class of genetic disorders characterized by impaired biochemical functions in metabolism. However, incidences and outcomes of patients hospitalized with IMDs are largely unknown. We conducted a population-based cohort study using nationwide in-hospital claims data in Switzerland from 2012 to 2020. We assessed incidence rates of hospitalizations and hospital-associated outcomes, stratified in five age groups (0-9, 10-19, 20-39, 40-59, and 60-90 years) and three types of IMDs (peptide, amine and amino acid metabolism disorders [AD], carbohydrate metabolism disorders [CD], fatty acid, and ketone body metabolism disorders [FD]). A total of 7293 hospitalizations with IMD were identified, of which 3638 had AD, 3153 CD, and 502 FD. Incidence rates for hospitalizations per 100 000 person-years were highest under the age of 10 years across all types of IMDs (8.69 for AD, 5.73 for CD, 3.71 for FD) and decreased thereafter. In patients with AD and CD, hospitalization rates increased again in adults aged 60-90 years (7.28 for AD, 7.25 for CD), while they remained low in patients with FD (0.31). Compared to inpatients without IMD, adult IMD patients had a higher burden of hospital-associated adverse outcomes including an increased risk of in-hospital mortality, intensive care unit admission, mechanical ventilation, and longer length of hospital or intensive care unit stay. Incremental risk of 30-day, 1-year, and 2-year hospital readmission was highest among children and adolescents with IMD.


Teriparatide Therapy Reduces Serum Phosphate and Intima-Media Thickness at the Carotid Wall Artery in Patients with Osteoporosis.
Although cross-sectional and longitudinal studies report a relationship between osteoporosis and cardiovascular disorders (known as the bone-cardiovascular axis), the benefits of osteoporosis treatment on atherosclerosis are largely unclear. Teriparatide is a bone-forming agent that increases urinary phosphate excretion. Because elevated serum phosphate is associated with the development of atherosclerosis, the purpose of our study was to examine the relationship among lumbar spine bone mineral density (LS-BMD), intima-media thickness at the carotid artery (CA-IMT), and phosphate metabolism in response to daily teriparatide therapy. Osteoporotic patients (n = 28) with low LS-BMD (T-score < -2.5) and/or at least one vertebral fracture were treated with teriparatide (20 μg/day) for 12 months. Metabolic bone markers, LS-BMD, and CA-IMT were measured over the course of treatment. The LS-BMD significantly increased by 0.046 ± 0.038 g/cm(2) over the 12-month period (P < 0.001). CA-IMT decreased from 0.701 mm (interquartile range: 0.655-0.774 mm) at baseline to 0.525 mm (0.477-0.670 mm) at 12 months (P < 0.05); however, CA-IMT change was not significantly associated with LS-BMD change. Serum phosphate decreased after 1 month of teriparatide administration, and the change in serum phosphate at 1 months was associated with the change in CA-IMT at 12 months (ρ = 0.431, P = 0.025). Teriparatide improved LS-BMD and CA-IMT, suggesting the existence of the bone-cardiovascular axis. The association between serum phosphate and CA-IMT suggests that the teriparatide decreased CA-IMT in part by reducing serum phosphate, a well-known vascular toxin, in addition to the improvement of bone-cardiovascular axis.


The use of unideterminant fragments of ferredoxin in the genetic mapping of determinant specificity of the immune response.
The ferredoxin (Fd) molecule is a small non-mammalian immunogenic protein containing 55 amino acid residues with only two major antigenic determinants located with the NH2-terminal heptapeptide and the COOH-terminal pentapeptide. Selective enzyme cleavages of Fd with either trypsin or carboxypeptidase A result in the inactivation of the antigenic determinants by the removal of a tripeptide at the NH2-terminal and two amino acid residues at the COOH-terminal, effectively leaving 52 and 53 amino acid fragments respectively, each containing a single antigenic determinant. Fd digested with both enzymes yielded a 50 amino acid peptide with both determinants inactivated. Purity of these digests was assessed using monoclonal antibodies in standard and antigen-blocking ELISAs. The doubly digested peptide had virtually no reactivity with anti-Fd sera, reconfirming that the central cysteine-rich region is serologically silent. It was found that the sum of the reactivities of the N- and C-determinant-bearing peptides as equal to that of the native Fd and that the ratio of the reactivities could be used to assess determinant selectivity in the response to Fd in congenic recombinant strains of mice. This method was used in mapping the determinant selectivity in the antibody response to the MHC of mice to the left of the I-B subregion. Use of the B10.HTT strain indicated that separate genes mapping to the same subregion code for the magnitude of the antibody response and the determinant selectivity of the response.


The reticular formation of lampreys (Petromyzonidae)--a target area for exohypothalamic vasotocinergic fibres.
The octapeptide vasotocin, which is formed in the classical neurosecretory nuclei of lampreys (Petromyzonidae), is transported, bound to the carrier protein neurophysin, not only to the neurohypophysis but also to various other regions of the brain via exohypothalamic fibres. A target area of this exohypothalamic vasotocinergic system is, in the brook lamprey (Lampetra planeri Bloch), a relatively well circumscribed area in the isthmus region of the rhombencephalic tegmentum motoricum, which is called area lateralis tegmenti. In this area, which belongs to the reticular formation, the vasotocinergic fibres form synaptic contacts with nerve cell perikarya and processes. The vesicles contained in the fibres were identified, ultrahistochemically, as neurophysin vesicles. They correspond to the neurophysin vesicles observed in the neurohypophysis of the same species. The functional significance of the vasotocinergic supply to portions of the reticular formation in lampreys is open to discussion.


The role of trust in COVID-19 vaccine hesitancy and acceptance among Black and White Americans.
Mass vaccination has been identified as the easiest way to combat the deadly spread of the coronavirus (COVID-19) disease, yet many Americans are still hesitant to be vaccinated. To understand motivations behind why someone is vaccine hesitant, we conceptualized a theoretical model in which demographic variables are positively associated with four types of trust (i.e., trust in institutions, physicians, non-discrimination, and social media). These trust variables, in turn, are positively associated with the outcome variable of vaccine acceptance. A multi-group structural equation modeling analysis of survey data from 1008 U.S. adults suggested that trust in institutions and physicians were important for both White and Black Americans in whether they were vaccine accepting or hesitant, while trust in non-discrimination was important for Black Americans and trust in social media was important for White Americans. Implications of the findings and how they can inform future vaccine campaigns are discussed.


The personality and health of King Henry VIII (1491-1547).
The projection of Henry VIII in the first half of his reign, which began in 1509, is of a magnificent and accomplished 'imperial prince', the possessor of superb physical health. In 1528, when aged 37, he showed a marked change in personality due, it is here argued, to depressive illness, from which he recovered by the mid-1530s. Such ill health has not been recognized previously and it engenders a need for a reassessment of his character and actions during these years of illness. He did not suffer from syphilis and the well-known leg ulcers were less incapacitating than has been described in the past. This truly enormous and overweight man was 55 years old when he died in 1547 in chronic heart failure.


Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: A systematic analysis of the literature.
Monoclonal antibodies against programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) are effective therapies in patients with non-small cell lung cancer (NSCLC). Herein, the authors performed a systematic review investigating differences in the toxicities of PD-1 and PD-L1 inhibitors. An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC. A formal systematic analysis was conducted with Comprehensive Meta-Analysis software (version 2.2). Clinical and demographic characteristics, response, and toxicity data were compared between both groups. A total of 23 studies reported between 2013 and 2016 were eligible for analysis. The total number of patients evaluated for toxicities was 3284 patients in the PD-1 group and 2460 patients in the PD-L1 group. The baseline patient characteristics of the 2 groups were similar, although there was a trend toward increased squamous histology in the group treated with PD-L1 (32% vs 25%; P = .6). There was no difference in response rate noted between PD-1 (19%) and PD-L1 (18.6%) inhibitors (P = .17). The incidence of overall adverse events (AEs) was comparable between the PD-1 and PD-L1 inhibitors (64% [95% confidence interval (95% CI), 63%-66%] vs 66% [95% CI, 65%-69%]; P = .8). Fatigue was the most frequently reported AE with both classes of drugs. Patients treated with PD-1 inhibitors were found to have a slightly increased rate of immune-related AEs (16% [95% CI, 14%-17%] vs 11% [95% CI, 10%-13%]; P = .07) and pneumonitis (4% [95% CI, 3%-5%] vs 2% [95% CI, 1%-3%]; P = .01) compared with patients who received PD-L1 inhibitors. In this systematic review involving 5744 patients with NSCLC, the toxicity and efficacy profiles of PD-1 and PD-L1 inhibitors appear to be similar. Cancer 2018;124:271-7. © 2017 American Cancer Society.


Regulation of antibody responses by rheumatoid factor. I. Polyclonal activation of human B cells by rheumatoid factor-containing preparations from seropositive plasma.
Rheumatoid factor (RF)-containing IgM preparations isolated from the plasma of two seropositive patients were able to increase the number of Ig-secreting cells in normal human peripheral blood lymphocyte cultures. This polyclonal B cell activation was optimal in the presence of both T cells and monocytes. A relationship was established between the activator and RF in these preparations based on the ability of both to bind to insolubilized human IgG. The presence of the activator also coincided with the presence of large, RF-containing Ig complexes. These data suggest that RF contributes to the formation of B cell-stimulating immune complexes--a phenomenon with possible negative consequences in disease states characterized by these complexes.


In vitro effects of chlorpromazine on microtubules and the Golgi complex in embryonic chick spinal ganglion cells: an electron microscopic study.
Spinal ganglia from 11-day-old chick embryos were incubated in media containing chlorpromazine (CPZ), lidocaine or D-amphetamine and subsequently examined by transmission electron microscopy. CPZ and lidocaine both caused a structural modification of the neuroblasts similar to that induced by the microtubular-disrupting drugs colchicine and vinblastine. That is, there was a partial disappearance of cytoplasmic microtubules with a concomitant increase in the number of microfilaments and the dictyosomes of the Golgi complex changed, with the number of narrow cisternae decreasing and the number of associated vacuoles increasing. Moreover, the dictyosomes were more distinctly separated from each other than in control ganglia. D-Amphetamine did not give rise to any clear changes in either the microtubular system or the Golgi complex and, furthermore, opposed the colchicine-like effects of CPZ. On the basis of these results it is suggested that the subcellular mechanism of action of CPZ involves the cytoplasmic microtubular system and thus secondarily leads to structural and functional alterations in the Golgi complex, viz., in the case of nerve cells, a disturbance in the production and packaging of material destined for the axon terminals.


High-Pressure Electrospray Ionization Yields Supercharged Protein Complexes from Native Solutions While Preserving Noncovalent Interactions.
Increasing charge state of protein complexes from native solutions while preserving noncovalent interactions in native mass spectrometry (MS) offers great opportunity to gain deeper insights into gas-phase protein structures. Several previous studies have disclosed the possibility of high pressure in supercharging small proteins, whereas its capability to supercharge large protein assemblies under native conditions and how it might affect protein structures remain open questions. Herein, we demonstrated that the high-pressure-induced supercharging strategy affords unique advantages of supercharging protein complexes with the highest charge state surpassing the Rayleigh limit (ZR) and concurrently preserving native-like topology. By examining 32 proteins and protein complexes with molecular weights (MWs) ranging from 8.58 to 801 kDa, we demonstrated that the increased average charge states of macromolecular ions have a strong dependence on the surface areas of native protein conformations and MWs. Factors that might contribute to the high-pressure-induced supercharging capability toward macromolecular ions were discussed. Furthermore, using collision cross section (CCS) variation as a function of charge state, we investigate the effects of gas pressure and charge states on gas-phase structures of proteins and protein complexes. Smaller proteins have the largest CCS variations once supercharged, while macromolecular protein complexes are less affected. The results revealed that both surface density of charge and charged surface basic residues contribute to the observed CCS-charge disciplines for all the macromolecules investigated. Taken together, the results presented here indicate that increasing gas pressure in the ion source affords a rapid, simple, and controlled supercharging method, offering the potency of facilitating further applications of native top-down MS analysis with improved transmission, fragmentation, and detection efficiency.


Otoacoustic emissions in ears with hearing loss.
Fifty ears of 37 patients demonstrating several common types of hearing impairment were examined for the presence of spontaneous and evoked otoacoustic emissions to investigate the relationship of acoustic emissions to hearing pathology. Of the 50 ears, 44 exhibited various degrees of sensorineural hearing loss. Evoked otoacoustic emissions to clicks were detected in 34 of 35 sensorineural hearing loss ears with a subjective click threshold less than 55 dB SPL (25 dB nHL). None of nine ears with sensorineural hearing impairment and a subjective click threshold greater than 55 dB SPL demonstrated click-evoked emissions. Spectral analyses revealed that the constituent frequency components of evoked emissions were always within the frequency range where audiometric thresholds were less than 35 dB HL, and in the majority (94%) of cases, thresholds were less than 25 dB HL. In ears with relatively well-preserved hearing within the frequency range of click or 1.5-kHz toneburst stimuli, the basic features of evoked emissions were similar to those described for normal ears. Similarly, for ears demonstrating spontaneous otoacoustic emissions, estimated audiometric thresholds at the emitted frequencies were always less than 20 dB HL. The influence of the type of otologic pathology on acoustic emissions was studied in a subset of ears exhibiting typical high-frequency hearing losses. Ears with a noise-induced impairment showed a significant reduction in the incidence of both spontaneous emissions and spectral peaks in evoked emissions that was not evident in ears with similar patterns of hearing loss caused by other factors.


Anatomical analysis of the cause of skin necrosis of the great toe after transplantation of the great toe nail flap.
Necrosis of skin on the medial side of the great toe has been a significant complication of the great toe nail flap. To investigate the reason for this, a study of the blood supply of the medial side of the great toe was carried out on 55 feet with the injection of red latex into the arteries and on 13 vascular cast specimens. It was found that, after the blood vessels from the plantar and dorsal sides of the great toe are severed during the operation, the skin of the medial side of the great toe is mainly supplied by the medial vascular network at the head of the first metatarsal bone. It is clear that the blood supply from this network may sometimes be insufficient to nourish the skin. It is suggested that the operative incision should be changed so as to increase the blood supply to the medial vascular network which may decrease the incidence of skin necrosis.


Chloroplast nitrite uptake is enhanced in Arabidopsis PII mutants.
In higher plants, the PII protein is a nuclear-encoded plastid protein that regulates the activity of a key enzyme of arginine biosynthesis. We have previously observed that Arabidopsis PII mutants are more sensitive to nitrite toxicity. Using intact chloroplasts isolated from Arabidopsis leaves and (15)N-labelled nitrite we show that a light-dependent nitrite uptake into chloroplasts is increased in PII knock-out mutants when compared to the wild-type. This leads to a higher incorporation of (15)N into ammonium and amino acids in the mutant chloroplasts. However, the uptake differences do not depend on GS/GOGAT activities. Our observations suggest that PII is involved in the regulation of nitrite uptake into higher plant chloroplasts.


(7-Ile) angiotensin III: a relatively selective antagonist of angiotensin steroidogenesis.
The effects of (7Ile) angiotensin III (AIII) and (1-Sar-8-Ile) angiotensin II (AII) on the pressor and steroidogenic effects of angiotensin were compared in conscious rats. (1-Sar-8-Ile) AII (500 ng/kg/min) equally inhibited the pressor responses of AII, AIII and (des-1-Asp) AI by 99% (P less than 0.0001) while (7-Ile) AIII (500 ng/kg/min) was without effect. The steroidogenic effects of AII, AIII and (des-1-Asp) AI (300 ng/kg/min) were inhibited by (1-Sar-8-Ile) AII by 83%, 69% and 50%, respectively, whereas (7-Ile) AIII inhibited their steroidogenic effects by 35%, 62% and 25%. respectively. In contrast, ACTH or potassium stimulated aldosterone release was not altered by either antagonist. In sodium depleted rats, (7-Ile) AII reduced the elevated serum aldosterone levels by 64% without altering the blood pressure, while (1-Sar-8-Ile) AII lowered the blood pressure without altering the concentration of aldosterone present in the serum. Thus, (7-Ile) AIII is relatively selective in its ability to antagonize the adrenal actions of endogenous and exogenous angiontensins when compared to the pressor actions of these peptides. Furthermore, these angiotensin antagonists appear to be useful as pharmacologic tools in assessing the characteristics of the angiotensin receptors in a particular tissue.


[The first experience of transporting a patient with severe respiratory failure in conditions of extracorporeal membrane oxygenation].
This publication is the first case report, in the Russian Federation aircraft evacuation of a patient with severe respiratory failure due to pneumonia of viral and bacterial etiology with the use of extracorporeal membrane oxygenation. The use of this method helped to stabilize the patient's condition and safely carry out transportation to a specialized medical institution for further treatment.


[Scanning electron microscopic study of the changes of the luminal surface of rat thyroid epithelial cells following exposure to cold for 6 to 48 hours (author's transl)].
Scanning electron microscopic observations of thyroid follicle cells of rats exposed to 4 degrees C for 6 to 48 hours were found to show an increased number of apical microvilli in comparison to those of controls kept at 22 degrees C. These ultrastructural differences--which were statistically significant 48 hours after start of the experiments--are related to stimulation of thyroid gland activity by exposure to cold.


TPpred-ATMV: therapeutic peptide prediction by adaptive multi-view tensor learning model.
Therapeutic peptide prediction is important for the discovery of efficient therapeutic peptides and drug development. Researchers have developed several computational methods to identify different therapeutic peptide types. However, these computational methods focus on identifying some specific types of therapeutic peptides, failing to predict the comprehensive types of therapeutic peptides. Moreover, it is still challenging to utilize different properties to predict the therapeutic peptides. In this study, an adaptive multi-view based on the tensor learning framework TPpred-ATMV is proposed for predicting different types of therapeutic peptides. TPpred-ATMV constructs the class and probability information based on various sequence features. We constructed the latent subspace among the multi-view features and constructed an auto-weighted multi-view tensor learning model to utilize the high correlation based on the multi-view features. Experimental results showed that the TPpred-ATMV is better than or highly comparable with the other state-of-the-art methods for predicting eight types of therapeutic peptides. The code of TPpred-ATMV is accessed at: https://github.com/cokeyk/TPpred-ATMV. Supplementary data are available at Bioinformatics online.


Systematic misidentification of toes in normal adults.
This note reports a previously unreported phenomenon: when subjects are asked to indicate subjective correspondence between fingers and toes, there is a remarkably systematic miscorrespondence, consistent across subjects. No satisfactory explanation for these findings has been found.


Conjugation of mono and di-GalNAc sugars enhances the potency of antisense oligonucleotides via ASGR mediated delivery to hepatocytes.
Antisense oligonucleotides (ASOs) conjugated to trivalent GalNAc ligands show 10-fold enhanced potency for suppressing gene targets expressed in hepatocytes. Trivalent GalNAc is a high affinity ligand for the asialoglycoprotein receptor (ASGR)-a C-type lectin expressed almost exclusively on hepatocytes in the liver. In this communication, we show that conjugation of two and even one GalNAc sugar to single stranded chemically modified ASOs can enhance potency 5-10 fold in mice. Evaluation of the mono- and di-GalNAc ASO conjugates in an ASGR binding assay suggested that chemical features of the ASO enhance binding to the receptor and provide a rationale for the enhanced potency.


The effect of exercise and motor interventions on physical activity and motor outcomes during and after medical intervention for children and adolescents with acute lymphoblastic leukemia: A systematic review.
Children with acute lymphoblastic leukemia (ALL) experience detrimental effects on motor function during and after chemotherapy. The objective of this systematic review was to evaluate the effect of exercise and motor interventions on physical activity and motor outcomes of children with ALL during and after chemotherapy. Ten databases were searched. Nineteen studies were included: 11 randomized clinical trials (RCT), 2 controlled clinical trials (CCT), and 6 cohort studies. Participants included 508 children with ALL. Between-group results from RCTs and CCTs supported that exercise and motor intervention improved: fatigue during acute chemotherapy; physical activity, range of motion (ROM), strength, bone mineral density, aerobic capacity, and fatigue during maintenance chemotherapy; functional mobility, ROM, strength, and aerobic capacity during post-treatment survivorship; and participation, physical activity, ROM, strength, and coordination during multiple-phase interventions. Low quality evidence supports the efficacy of motor and exercise interventions for children and adolescents with ALL.


Direct MOCVD Growth of Iron Oxide on Three-Dimensional Nickel Foam as Electrode for the Oxygen Evolution Reaction.
Iron oxide thin films were grown directly on three-dimensional nickel foam via metalorganic chemical vapor deposition (MOCVD) in the temperature range of 250-450 °C using Fe(CO)5 as precursor. Iron oxide (α-Fe2 O3 ) films were formed at low substrate temperatures (250-350 °C), whereas the additional growth of an underlying NiO film occurred at substrate temperatures above 350 °C. The electrochemical activities of the as-formed binder-free and noble metal-free electrodes were tested for the oxygen evolution reaction (OER) in alkaline media. An overpotential reduced by 250 mV at a current density of 50 mA cm-2 and a lower Tafel slope of 55 mV dec-1 compared to bare nickel foam were found for the best-performing electrocatalyst, while the long-term stability of the as-formed electrodes was proven by chronopotentiometry. The surface morphology of the iron oxide films was characterized by scanning electron microscopy, whereas the crystallographic phase as well as the elemental composition were determined by X-ray diffraction, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and time-of-flight secondary ion mass spectrometry in the pre- and the post-catalytic state.


TFPI2 suppresses the interaction of TGF-β2 pathway regulators to promote endothelial-mesenchymal transition in diabetic nephropathy.
Endothelial-mesenchymal transition (EndMT) is an important source of myofibroblasts, but also contributes to the progression of diabetic nephropathy (DN). By several differential gene expression analyses from the Gene Expression Omnibus (GEO) database, the tissue factor pathway inhibitor 2 (TFPI2) gene, known as a tumor suppressor, was shown to be dysregulated in DN; however, the potential role and regulatory mechanism of TFPI2 in DN are unclear. Here, we found abnormal upregulation of TFPI2 in the renal cortex of diabetic mice, accompanied by impaired renal function. We also injected a single dose of adeno-associated virus (AAV)2 carrying shRNA targeting TFPI2 intravenously into these mice and found that knockdown of TFPI2 improved renal function and reduced renal fibrosis and cell apoptosis in experimental DN. Furthermore, hyperglycemia-induced EndMT was inhibited in the absence of TFPI2, as evidenced by increased expression of endothelial markers (VE-cadherin and CD31) and decreased expression of mesenchymal markers (α-SMA, desmin, and FSP-1). To further explore the mechanism in vitro, human renal glomerular endothelial cells (hRGECs) were incubated in the presence of high glucose or transforming growth factor beta (TGF-β)2. TFPI2 deficiency inhibited high glucose-induced cell apoptosis and TGF-β2-induced EndMT in hRGECs, while overexpression of TFPI2 had the opposite effects. Importantly, TGF-β2 is a crucial driver of EndMT, and we found that TFPI2 promoted TGF-β2/Smad signaling activation by interferring the interaction of TGF-β pathway regulators (SMURF2 with SMAD7). Our results show that TFPI2 regulates EndMT and the TGF-β2 signaling pathway and is a potential promoter of DN pathogenesis.


Lathyrus sativus diamine oxidase reduces Clostridium difficile toxin A-induced toxicity in Caco-2 cells by rescuing RhoA-GTPase and inhibiting pp38-MAPK/NF-κB/HIF-1α activation.
Clostridium difficile toxin A (TcdA) impairs the intestinal epithelial barrier, increasing the mucosa permeability and triggering a robust inflammatory response. Lathyrus sativus diamino oxidase (LSAO) is a nutraceutical compound successfully used in various gastrointestinal dysfunctions. Here, we evaluated the LSAO (0.004-0.4 μM) ability to counter TcdA-induced (30 ng/mL) toxicity and damage in Caco-2 cells, investigating its possible mechanism of action. LSAO has improved the transepithelial electrical resistance (TEER) score and increased cell viability in TcdA-treated cells, significantly rescuing the protein expression of Ras homolog family members, A-GTPase (RhoA-GTPase), occludin, and zonula occludens-1 (ZO-1). LSAO has also exhibited an anti-apoptotic effect by inhibiting the TcdA-induced expression of Bcl-2-associated X protein (Bax), p50 nuclear factor-kappa-B (p50), p65nuclear factor-kappa-B (p65), and hypoxia-inducible transcription factor-1 alpha (HIF-1α), and the release of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) in the cell milieu. Our data showed that LSAO exerts a protective effect on TcdA-induced toxicity in Caco-2 cells, placing itself as an interesting nutraceutical to supplement the current treatment of the Clostridium difficile infections.


Toll-like receptor 4 selective inhibition in medullar microenvironment alters multiple myeloma cell growth.
Bone marrow (BM) mesenchymal stromal cells (MSCs) are abnormal in multiple myeloma (MM) and play a critical role by promoting growth, survival, and drug resistance of MM cells. We observed higher Toll-like receptor 4 (TLR4) gene expression in MM MSCs than in MSCs from healthy donors. At the clinical level, we highlighted that TLR4 expression in MM MSCs evolves in parallel with the disease stage. Thus, we reasoned that the TLR4 axis is pivotal in MM by increasing the protumor activity of MSCs. Challenging primary MSCs with TLR4 agonists increased the expression of CD54 and interleukin-6 (IL-6), 2 factors directly implicated in MM MSC-MM cell crosstalk. Then, we evaluated the therapeutic efficacy of a TLR4 antagonist combined or not with conventional treatment in vitro with MSC-MM cell coculture and in vivo with the Vk*MYC mouse model. Selective inhibition of TLR4 specifically reduced the MM MSC ability to support the growth of MM cells in an IL-6-dependent manner and delayed the development of MM in the Vk*MYC mouse model by altering the early disease phase in vivo. For the first time, we demonstrate that specific targeting of the pathological BM microenvironment via TLR4 signaling could be an innovative approach to alter MM pathology development.


Polymorphisms in the interleukin-10, tumor necrosis factor-alpha, and transforming growth factor-beta1 genes in chronic hepatitis C patients treated with interferon and ribavirin.
In hepatitis C infection, the production of inappropriate cytokine levels appears to contribute to viral persistence and to affect the response to antiviral therapy. Additionally, polymorphisms in the cytokine genes may affect the production of the cytokines. In this study, we determined the frequency of the genotypes associated with polymorphisms of the interleukin-10 and tumor necrosis factor-alpha gene promoters, and transforming growth factor-beta 1 gene leader sequence, and investigated their association with clinical features and the response to interferon-alpha and ribavirin therapy in chronic hepatitis C infection. Genomic DNA from 80 patients and 37 racially matched healthy controls was studied by polymerase chain reaction and direct automated sequencing. The interleukin-10 -1082 G/G genotype was identified more frequently in patients than in controls (P=0.048). The transforming-growth factor-beta 1 +29 (codon 10) C/C genotype was associated with resistance to the therapy (P=0.029). After adjusting for potential confounding variables, patients exhibiting the C/C genotype were less likely to respond to treatment than patients with the T/T or T/C genotypes. These results suggest that inheritance of the interleukin-10 -1082 G/G and the transforming growth factor-beta 1 +29 C/C genotypes, which appear to affect the cytokine production, may be associated with susceptibility to chronic hepatitis C infection and resistance to combined antiviral therapy.


How do Ca2+ ions pass through the sarcoplasmic reticulum membrane.
We propose an overview of the mechanism of Ca2+ transport through the sarcoplasmic reticulum membrane via the Ca(2+)-ATPase. We describe cytoplasmic calcium binding, calcium occlusion in the membrane and lumenal calcium dissociation. A channel-like structure is discussed and related to structural data on the membranous domain of the Ca(2+)-ATPase.


Peer group-based online intervention program to empower families raising children with disabilities: protocol for a feasibility study using non-randomized waitlist-controlled trial.
Families raising children with disabilities assume risks to their health and lives. Therefore, it is necessary to support these families to improve family empowerment, which is the ability of these families to control their own lives and to promote the collaborative raising of children with disabilities. This is the first online intervention program focusing on the empowerment of families raising children with disabilities who live at home in Japan. The program consists of four online peer-based group sessions. Moreover, the families engage in several activities in stages wherein they discover their own issues, find measures to resolve them, and take action, while visualizing interfamily relationships, including social resources, and the status of their family life, with facilitators and other peer members. This study is a non-randomized, waitlist-controlled trial. It compares the results of the intervention group (early group) and the waitlist-controlled group (delayed group). The participants are allocated to the early or delayed group in the order of their applications. The main outcome is family empowerment. Other outcomes are the caregiver burden, self-reported capability to use social resources, self-compassion, and the quality of life (QOL) of primary caregivers. The timeline of the online outcome evaluation is as follows: the initial evaluation (Time 1 [T1]) is conducted before the start of the first early group program, and post-intervention evaluation (Time 2 [T2]) is conducted immediately (within 1 week) after the early group completes all four sessions (4 weeks) of the program. Follow-up evaluation (Time 3 [T3]) is conducted 4 weeks after the post-intervention evaluation. This timing is the same in the delayed group, but the delayed group will attend the program after a 4-week waiting period, compared to the early group. The intention is to evaluate whether the provision of the program developed in this study and the evaluation test design are feasible and to verify the efficacy of this program. The UMIN Clinical Trials Registry (UMIN000044172), registration date: May 19, 2021.


Uncoupling of Vascular Endothelial Growth Factor (VEGF) and Inducible Nitric Oxide Synthase (iNOS) in Gingival Tissue of Type 2 Diabetic Patients.
In this study, we investigate the relation between vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) in periodontal disease of diabetic and non-diabetic individuals. We evaluated immunohistochemical VEGF and iNOS expressions in gingival biopsies from healthy individuals (no chronic periodontitis (CP)), patients with periodontitis alone (CP), patients with diabetes alone (DM) and diabetic patients with chronic periodontitis (DM + CP). We found a significant positive correlation between VEGF and iNOS expression in non-diabetic groups, but not in diabetic ones. Periodontal clinical parameters were not found to be significantly correlated with the inflammatory markers in no-CP, CP, and DM groups, whereas in DM + CP, positive and significant correlations were found between all the considered periodontal parameters and epithelial VEGF and endothelial iNOS. The uncoupling of VEGF and iNOS expression in diabetic individuals could allow a greater involvement of the markers in the inflammatory process of periodontitis.


Vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg viruses.
Considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against Ebola and Marburg viruses. A vaccine based on recombinant vesicular stomatitis virus (VSV) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. While filoviruses are not thought to be transmitted by aerosol in nature the inhalation route is among the most likely portals of entry in the setting of a bioterrorist event. At present, all candidate filoviral vaccines have been evaluated against parenteral challenges but none have been tested against an aerosol exposure. Here, we evaluated our recombinant VSV-based Zaire ebolavirus (ZEBOV) and Marburg virus (MARV) vaccines against aerosol challenge in cynomolgus macaques. All monkeys vaccinated with a VSV vector expressing the glycoprotein of ZEBOV were completely protected against an aerosol exposure of ZEBOV. Likewise, all monkeys vaccinated with a VSV vector expressing the glycoprotein of MARV were completely protected against an aerosol exposure of MARV. All control animals challenged by the aerosol route with either ZEBOV or MARV succumbed. Interestingly, disease in control animals appeared to progress slower than previously seen in macaques exposed to comparable doses by intramuscular injection.


Successful induction of clinically competent dendritic cells from granulocyte colony-stimulating factor-mobilized monocytes for cancer vaccine therapy.
Recent studies have suggested that dendritic cell (DC)-based immunotherapy is one promising approach for the treatment of cancer. We previously studied the clinical toxicity, feasibility, and efficacy of cancer vaccine therapy with peptide-pulsed DCs. In that study, we used granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood monocytes as a cell source of DCs. However, previous investigations have suggested that G-CSF-mobilized peripheral blood monocytes produce reduced levels of proinflammatory cytokines such as interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha. These T helper (Th)-1-type cytokines are thought to promote antitumor immune response. In this study, we assessed the functional abilities of DCs generated from G-CSF-mobilized monocytes obtained from 13 patients with CEA-positive advanced solid cancers. Peripheral blood mononuclear cells were obtained from leukapheresis products collected before and after systemic administration of G-CSF (subcutaneous administration of high-dose [5-10 microg/kg] human recombinant G-CSF for five consecutive days). In vitro cytokine production profiles after stimulation with lipopolysaccharide (LPS) were compared between monocytes with and without G-CSF mobilization. DCs generated from monocytes were also examined with respect to cytokine production and the capacity to induce peptide-specific T cell responses. Administration of G-CSF was found to efficiently mobilize peripheral blood monocytes. Although G-CSF-mobilized monocytes (G/Mo) less effectively produced Th-1-type cytokines than control monocytes (C/Mo), DCs generated from G/Mo restored the same level of IL-12 production as that seen in DCs generated from C/Mo. T cell induction assay using recall antigen peptide and phenotypic analyses also demonstrated that DCs generated from G/Mo retained characteristics identical to those generated from C/Mo. Our results suggest that G-CSF mobilization can be used to collect monocytes as a cell source for the generation of DCs for cancer immunotherapy. DCs generated in this fashion were pulsed with HLA-A24-restricted CEA epitope peptide and administered to patients safely; immunological responses were induced in some patients.


Langendorff-Isolated Rat Heart after Acute Experimental Myocardial Infarction.
A comparative analysis of functioning of Langendorff-isolated heart from intact rats, sham-operated rats, and rats with a model of myocardial infarction one day after ligation of the left coronary artery was carried out. No significant differences in inotropic and chronotropic functions of the heart were found in the groups of intact and sham-operated animals. In the group of rats with the myocardial infarction model, an increase in HR and a decrease in the maximum contraction and relaxation rates and left-ventricular developed pressure were shown in comparison with the groups of intact and sham-operated animals. At the same time, in the group of sham-operated animals, a decrease in coronary flow and temporal parameters of contraction was observed.


Toxicity of Silver Nanoparticles in the Presence of Zinc Oxide Nanoparticles Differs for Acute and Chronic Exposures in Zebrafish.
We assessed the acute toxicity effects (96 h) of silver nanoparticles (Ag NPs) and zinc oxide nanoparticles (ZnO NPs) and chronic (28 d) exposure to Ag NPs, including in combination with ZnO NPs. In the chronic studies, we further assessed the toxicokinetics and bioaccumulation of Ag and the resulting histopathological effects in the gill, intestine, and liver of zebrafish. Co-exposures with ZnO NPs reduced the toxicity of Ag NPs for acute (lethality) but enhanced the toxicity effects (tissue histopathology) for chronic exposures. The histological lesions for both NPs exposures in the gill included necrosis and fusion of lamellae, for the intestine necrosis and degeneration, and in the liver, mainly necrosis. The severity of the histological lesions induced by the Ag NPs was related to the amount of accumulated Ag in the zebrafish organs. The Ag accumulation in different organs was higher in the presence of ZnO NPs in the order of the gill > intestine > liver. Depuration kinetics illustrated the lowest half-life for Ag occurred in the gill and for the combined exposure of Ag with ZnO NPs. Our findings illustrate that in addition to tissue, time, and exposure concentration dependencies, the Ag NPs toxicity can also be influenced by the co-exposure to other NPs (here ZnO NPs), emphasizing the need for more combination exposure effects studies for NPs to more fully understand their potential environmental health risks.


Electroluminescent display visual stimulator - a new method for visual evoked potential studies.
A new atomic layer epitaxy electroluminescent display visual stimulator for visual evoked potential studies is described. The display has several advantages over TV monitor stimulators, slide and projector stimulators and LED stimulators. The display is versatile, various patterns, letters or even words may be generated. The display has short rise and decay times, a high and stable luminosity.


Radiology-pathology conference: malignant solitary fibrous tumor of the seminal vesicle.
Mesenchymal neoplasms are rarely encountered in the seminal vesicle. Only four cases of the seminal vesicle solitary fibrous tumor have been reported in English literature, all of which were benign in nature. We are describing the clinicoradiological and pathological features of a locally aggressive malignant solitary fibrous tumor arising from the seminal vesicle, which posed the therapeutic challenge for the surgical management in a 52-year-old male patient. To our knowledge, this is the first reported case of the malignant solitary fibrous tumor arising from the seminal vesicle.