Effect of protein-bound uraemic toxins on the thermodynamic characteristics of human albumin.
The ability of albumin to bind drugs and other lipophilic organic acids is decreased in chronic renal failure by the accumulation of albumin-bound uraemic toxins such as hippuric acid, indoxyl sulphate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF). This furan acid is the most highly bound and is not removed by haemodialysis. The inhibitory effects of these three uraemic toxins on the interaction of three marker ligands sodium octanoate (for medium chain fatty acids), salicylic acid and phenol red (bilirubin site/site I) with albumin have been investigated by differential scanning microcalorimetry and flow microcalorimetry. CMPF was the most potent inhibitor and its binding site coincided with that of bilirubin (site I). Indoxyl sulphate binds to the site for medium-chain fatty acids and tryptophan (site II) and hippuric acid, the weakest inhibitor, inhibited binding to the salicylic acid site.


Laparoscopic radical cystectomy for bladder cancer with prostatic and neurovascular sparing: initial experience.
This study presents our initial experience with laparoscopic radical cystectomy with preservation of the neurovascular bundles and partial prostate for the treatment of bladder cancer. Thirty-seven patients with bladder cancer were selected for the study between June 2007 and December 2009. The criteria for patient selection included prostate-specific antigen level below 4.0 ng/mL; negative involvement of the trigone and/or prostatic urethra; and no self-reported erectile dysfunction. The surgical procedure included laparoscopic prostate- and neurovascular bundles-sparing cystectomy with an ileal neobladder construction. Mean follow-up was 18 months. All patients underwent laparoscopic resection without requiring a traditional open procedure. The mean operation time was 215 min with a mean volume of intraoperative hemorrhage of 190 mL. After removal of the urinary catheter, all patients had a daytime urinary continence; six had a short period of nighttime urinary incontinence. Most patients reported a strong desire for sexual activity and were able to complete sexual intercourse without auxiliary measures at 3 months postoperatively. Grade-3 complications developed in 2 patients graded by the classification of Clavien system. One patient was diagnosed with pelvic recurrence 16 months postoperatively. The laparoscopic radical cystectomy with a partial prostate preservation offers the advantages of a high continence, minimal impairment of erectile function, and low recurrence rate.


Radiolead (210)Pb and (210)Po/(210)Pb activity ratios in calcium supplements and the assessment of their possible dose to consumers.
This paper presents the results of pioneer study of the most popular calcium supplements as a potential additional source of radiolead (210)Pb in human diet. The analyzed calcium pharmaceutics contained organic or inorganic calcium compounds; some came from natural sources as mussels' shells, fish extracts, or sedimentary rocks. The idea was to investigate the naturally occurring (210)Pb activity in different calcium supplements and calculate the annual effective radiation dose from radiolead (210)Pb decay in consumed calcium supplement. The results showed (210)Pb concentrations in natural origin calcium supplements (especially sedimentary rocks) were significantly higher. The highest (210)Pb activity concentrations were determined in mineral tablets made from dolomite - 2.97 ± 0.18 mBq g(-1), while the lowest was observed in organic calcium compounds - both calcium lactate - 0.08 ± 0.01 and 0.13 ± 0.01 mBq g(-1). The highest annual radiation dose from (210)Pb taken with 1 tablet of calcium supplement per day was calculated for soluble calcium lactate sample - 1.19 ± 0.03 µSv year(-1), while the highest annual radiation dose from (210)Pb taken daily with 1 g of pure Ca for dolomite - 5.57 ± 0.34 µSv year(-1).


[Determination of zearalenone in edible oils with SEC and LC-ESI-MS/MS].
A new method for the determination of zearalenone in edible oils with size exclusion chromatography (SEC) followed by LC-MS/MS as well as HPLC-FLD was developed and validated. By using the LC-MS/MS determination no further clean up step is necessary after the SEC. The correlation coefficient of 0.999 for the two detection systems is acceptable. In this research 77 edible oils were analyzed. The mean average value of 38 corn germ oils was 169 μg/kg, the maximum value amounted up to 921 μg/kg.


Mapping of cytochrome P450 2B4 substrate binding sites by photolabile probe 3-azidiamantane: identification of putative substrate access regions.
To investigate structure-function relationships of cytochromes P450 (CYP), 3-azidiamantane was employed for photoaffinity labeling of rabbit microsomal CYP2B4. Four diamantane labeled tryptic fragments were identified by mass spectrometry and sequencing: peptide I (Leu359-Lys373), peptide II (Leu30-Arg48), peptide III (Phe127-Arg140), and peptide IV (Arg434-Arg443). Their positions were projected into CYP2B4 model structures and compared with substrate binding sites, proposed by docking of diamantane. We identified novel binding regions outside the active site of CYP2B4. One of them, defined with diamantane modified Arg133, marks a possible entrance to the active site from the heme proximal face. In addition to crystal structures of CYP2B4 chimeras and molecular dynamics simulations, our data of photoaffinity labeling of the full CYP2B4 molecule provide further insight into functional and structural aspects of substrate binding.


An ultrasonic study of the thermotropic transition of dipalmitoyl phosphatidylcholine.
The acoustic absorption of sonicated and unsonicated suspensions of dipalmitoyl phosphatidylcholine has been studied as a function of temperature at frequencies between 0.6 and 4.0 MHz. The absorption at a fixed frequency passes through a maximum at a temperature which is dependent on the sample preparation and history and somewhat dependent on the frequency of observation, with sonicated vesicles exhibiting a temperature of maximum absorption 2--3 degrees C below that found for unsonicated dispersions. The temperature dependence of the absorption at fixed frequency suggests a cooperative process while the frequency dependence of the absorption at fixed temperature indicates that more than a single relaxation time is required to describe the acoustic absorption.


Psychometric evaluation of the hope, agency and opportunity (HAO); a brief measure of mental health recovery.
The development of safe and effective mental health services is a priority. This requires valid measures of personal recovery, yet these tools are not embedded in routine clinical practice. Brief "patient reported measures" are most likely to be acceptable to service-users and clinicians. The 4-item "Hope, Agency and Opportunity" (HAO) was co-produced to assess recovery outcomes and experience of mental health services. To evaluate the psychometric properties of the HAO. A clinical sample from secondary healthcare services and a non-clinical sample were assessed at baseline and two weeks, on measures of personal recovery. Factor analysis indicated goodness of fit for the HAO with both clinical and non-clinical samples. The measure demonstrated acceptable internal consistency, moderate to strong construct validity and substantial test-retest reliability over two weeks. The HAO demonstrates satisfactory psychometric properties. Co-production of the measure confers clinical credibility. The brevity of the tool means it can be incorporated into routine clinical practice to drive improvements in service quality.


The effect of CoolClot hemostatic agent on skin wound healing in rats.
Hemostatic agents can play a key role in controlling severe hemorrhage after trauma. Previously, some criteria have been defined for improving the quality of these products; one of them is that the hemostat causes no further tissue injury. CoolClot is a recently introduced hemostatic agent that its effects on wound healing have not yet been examined, which this study aims to address. Thirty-four adult male Sprague-Dawley rats were assigned randomly to two groups (n = 17): a study group where CoolClot hemostatic agent was applied on their wounds, and a control group whose wounds were washed only with sterile saline. The rats underwent dorsal full-thickness skin excisional wounds (20 mm diameter). On day 12 after wounding, seven rats were chosen in a random manner from each of the groups of study and control, and their skin biopsies from the wound sites were sent for histologic examination. Skin samples of the remaining rats in each group were taken on the 21st d after wound creation. Wound healing was also monitored photographically. In addition, wound surface temperature after wounding, and the application of CoolClot was recorded. There was no significant difference between the groups of study and control regarding the examined histopathologic parameters. The maximum increase in wound surface temperature was 1.56°C. One-time topical usage of CoolClot has no significant negative effect on the wound healing process. In addition, no significant increase in wound surface temperature will occur after the application of this agent.


Humanization of Camelid Single-Domain Antibodies.
Humanization of therapeutic antibodies derived from animal immunizations is often required to minimize immunogenicity risks in humans, which can cause potentially harmful and serious side effects and reduce antibody efficacy. Humanization is typically applied to conventional monoclonal antibodies derived in rodents as well as single-domain antibodies isolated from camelids and sharks (VHHs and VNARs). A streamlined protocol is described here for sequence humanization of camelid VHHs, which represent a promising biotherapeutic format with many desirable attributes. From human framework selection and complementarity-determining region grafting strategies to empirical scoring for prioritization of back-mutations, step-by-step instructions, and templates are provided along with bioinformatics resources to assist each step of the humanization process. Alternative approaches, warnings, and caveats are also presented.


Effects of superior mesenteric and coeliac ganglionectomy on peptide-producing cells of the small intestinal mucosa in the Hanford mini pig. II. Immunohistochemical study.
Superior mesenteric and coeliac ganglionectomy was performed in 5 Hanford mini pigs and cholecystokinin (CCK)-immunoreactive I-cells, neurotensin (NT)-immunoreactive N-cells, glucagon (Glu)-immunoreactive L-cells, glicentin (Glic)-immunoreactive L-cells and somatostatin (Som)-immunoreactive D-cells were quantitatively evaluated in the duodenum, the upper, middle and lower jejunum and the ileum before, 3 weeks and 6 months after ganglionectomy. Three additional animals served as controls. After ganglionectomy, I-cell numbers increase by 110% in the upper jejunum and duodenum; N-cells increase by 86% in the lower jejunum. Glu- and Glic-immunoreactive L-cells decrease slightly in the jejunum. In contrast, D-cells decrease in all sections of the small intestine by 44-76% (P less than 0.05 and P less than 0.001). All the examined entero-endocrine cells, except the D-cells in the duodenum and upper jejunum, develop hypertrophy after ganglionectomy. No changes either in number or size are found in the ganglia and neurons of the myenteric plexus. From these and the recently described increase in villus height and absorptive cells and absorptive cell enzymes after ganglionectomy (Holle, G.E. et al. Effects of superior mesenteric and coeliac ganglionectomy on the mucosa of the small intestine in the Hanford mini pig. I. Histological and enzymhistochemical study, J. Auton. Nerv. Syst., 26 (1988) 135-145), we conclude that the extrinsic nervous system takes suppressive influence on structure and probably function of the small intestinal mucosa by modifying its cellular organization.


Nursing Reports: Annual Report Card 2020.
The choices authors make about where to submit their papers are complicated but are typically based on the Journal's prestige [...].


Patterns of projections from the pontine nuclei and the nucleus reticularis tegmenti pontis to the posterior vermis in the rhesus monkey: a study using retrograde tracers.
In an attempt to estimate the relative importance of the various afferent systems impinging on the oculomotor regions of the posterior cerebellar vermis of rhesus monkeys in quantitative terms, we made small injections of the retrograde tracers fast blue, fluorogold, and cholera toxin into different parts of a region of the posterior vermis, spanning lobuli VI through VIII. We found that the vast majority of cells retrogradely labeled by injections of lobulus VII and its vicinity lay in the pontine nuclei (PN), the nucleus reticularis tegmenti pontis (NRTP), and subnuclei a and b of the medial accessory olive. The remaining retrogradely labeled cells were distributed among a number of other brainstem nuclei or regions including the paramedian pontine reticular formation (PPRF). A quantitative analysis showed that the projection from the NRTP to the posterior vermis was focused on lobulus VII. While the projection from the PN as a whole demonstrated a preference for the more caudal parts of the posterior vermis, a closer look at the different regions of the PN revealed that cells located in the dorsal parts of the PN showed the same preference for lobulus VII as cells in the NRTP. The dorsal PN are a major gateway for cortical input to the cerebellum, related to visual processing and visually guided eye movements. Conversely, the NRTP, likewise involved in visually guided eye movements, is much more dependent on subcortical afferents. The observed convergence of input derived from the dorsal PN and the NRTP in oculomotor lobulus VII therefore suggests that a major function of this part of the vermis might be the integration of cortical and subcortical signals important for visually guided eye movements.


Fetal growth restriction but not preterm birth is a risk factor for severe hypospadias.
Hypospadias has multifactorial causes and occurs at a high frequency among very low-birthweight infants. Placental insufficiency is hypothesized to be one cause of hypospadias; that is, decreased human chorionic gonadotropin (hCG) secretion caused by placental insufficiency is suspected to result in abnormal male external genitalia, but there is little direct evidence to support this. The aim of this study was therefore to identify the features of hypospadias and to clarify the male genital abnormalities caused by fetal growth restriction (FGR). We reviewed the clinical data of boys who underwent hypospadias repair between 2005 and 2011 at Kyoto University Hospital. Twenty boys were included in this study. Fifteen (75%) of the subjects were preterm or low-birthweight infants. Thirteen (65%) had FGR, 60% of whom had severe hypospadias regardless of gestational age. In addition, 92% of the FGR infants also had other genital anomalies, such as cryptorchidism, bifid scrotum, or micropenis. In contrast, only 14% and 43% of the non-FGR infants had severe hypospadias or genital anomalies other than hypospadias, respectively. Placental histopathology was available in eight FGR infants, in seven of whom it was suggestive of blood flow deficiency such as infarction and single umbilical artery. Infants with FGR have a high incidence of hypospadias. FGR caused by placental dysfunction, but not low birthweight, is a risk factor for severe hypospadias associated with multiple genital anomalies.


[Proliferation of hamster embryo fibroblast cultures infected with the herpes simplex virus].
In the HEF system in logarythmic and stationary phases of the culture growth the type-2 herpes simplex virus serves as a stimulator of proliferative processes in the cell (there is an increase of the labelled cells index, mitotic index and the intensity of labelling). The capacity of herpes virus not to suppress the cell DNA synthesis, as infestious viruses do, but to stimulate poliferative abilities of the cell indicates a presumable potential oncogenicity of this virus.


Bacterial synthesis of N-hydroxycinnamoyl phenethylamines and tyramines.
Hydroxycinnamic acids (HCAs) including cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid, are C6-C3 phenolic compounds that are synthesized via the phenylpropanoid pathway. HCAs serve as precursors for the synthesis of lignins, flavonoids, anthocyanins, stilbenes and other phenolic compounds. HCAs can also be conjugated with diverse compounds including quinic acid, hydroxyl acids, and amines. Hydroxycinnamoyl (HC) amine conjugates such as N-HC tyramines and N-HC phenethylamines have been considered as potential starting materials to develop antiviral and anticancer drugs. We synthesized N-HC tyramines and N-HC phenethylamines using three different approaches in Escherichia coli. Five N-HC phenethylamines and eight N-HC tyramines were synthesized by feeding HCAs and phenethylamine or tyramine to E. coli harboring 4CL (encoding 4-coumarate CoA:ligase) and either SHT (encoding phenethylamine N-HC transferase) or THT (encoding tyramine N-HC transferase). Also, N-(p-coumaroyl) phenethylamine and N-(p-coumaroyl) tyramine were synthesized from p-coumaric acid using E. coli harboring an additional gene, PDC (encoding phenylalanine decarboxylase) or TDC (encoding tyrosine decarboxylase). Finally, we synthesized N-(p-coumaroyl) phenethylamine and N-(p-coumaroyl) tyramine from glucose by reconstructing the metabolic pathways for their synthesis in E. coli. Productivity was maximized by optimizing the cell concentration and incubation temperature. We reconstructed the metabolic pathways for synthesis of N-HC tyramines and N-HC phenethylamines by expressing several genes including 4CL, TST or SHT, PDC or TDC, and TAL (encoding tyrosine ammonia lyase) and engineering the shikimate metabolic pathway to increase endogenous tyrosine concentration in E. coli. Approximately 101.9 mg/L N-(p-coumaroyl) phenethylamine and 495.4 mg/L N-(p-coumaroyl) tyramine were synthesized from p-coumaric acid. Furthermore, 152.5 mg/L N-(p-coumaroyl) phenethylamine and 94.7 mg/L N-(p-coumaroyl) tyramine were synthesized from glucose.


Changes in a sensorimotor network, occipital network, and psychomotor speed within three months after focal surgical injury in pediatric patients with intracranial space-occupying lesions.
Studies on cognition and brain networks after various forms of brain injury mainly involve traumatic brain injury, neurological disease, tumours, and mental disease. There are few related studies on surgical injury and even fewer pediatric studies. This study aimed to preliminarily explore the cognitive and brain network changes in children with focal, unilateral, well-bounded intracranial space-occupying lesions (ISOLs) in the short term period after surgery. We enrolled 15 patients (6-14 years old) with ISOLs admitted to the Department of Pediatric Neurosurgery of the Beijing Tiantan Hospital between July 2020 and August 2021. Cognitive assessment and resting-state functional magnetic resonance imaging (rs-fMRI) were performed. Regional homogeneity (Reho), seed-based analysis (SBA) and graph theory analysis (GTA) were performed. Paired T-test was used for statistical analysis of cognitive assessment and rs-fMRI. Gaussian random-field theory correction (voxel p-value < 0.001, cluster p-value < 0.05) was used for Reho and SBA. False discovery rate correction (corrected p value < 0.05) for GTA. Our results showed that psychomotor speed decreased within three months after surgery. Further, rs-fMRI data analysis suggested that sensorimotor and occipital network activation decreased with low information transmission efficiency. We prudently concluded that the changes in cognitive function and brain network within three months after surgery may be similar to ageing and that the brain is vulnerable during this period.


Nitric oxide metabolites are not reduced in exhaled breath condensate of patients with primary ciliary dyskinesia.
To investigate whether nitric oxide (NO) metabolites would be reduced in children affected by primary ciliary dyskinesia (PCD). Single-center observational study. Fifteen children with PCD (seven boys; mean [+/- SEM] age, 10.3 +/- 0.7 years; mean FEV(1), 73 +/- 2.1% predicted) were recruited along with 14 healthy age-matched subjects (seven boys; mean age, 11.5 +/- 0.4 years; mean FEV(1), 103 +/- 5% predicted). We assessed the levels of nitrite (NO(2)(-)), NO(2)(-)/NO(3)(-) (NO(2)(-)/NO(3)(-)), and S-nitrosothiol in exhaled breath condensate, exhaled NO, and nasal NO from children with PCD compared to those in healthy children. The mean exhaled and nasal NO levels were markedly decreased in children with PCD compared to those without PCD (3.2 +/- 0.2 vs 8.5 +/- 0.9 parts per billion [ppb], respectively [p < 0.0001]; 59.6 +/- 12.2 vs 505.5 +/- 66.8 ppb, respectively [p < 0.001]). Despite the lower levels of exhaled NO in children with PCD, no differences were found in the mean levels of NO(2)(-) (2.9 +/- 0.4 vs 3.5 +/- 0.3 microM, respectively), NO(2)(-)/NO(3)(-) (35.2 +/- 5.0 vs 34.3 +/- 4.5 microM, respectively), or S-nitrosothiol (1.0 +/- 0.2 vs 0.6 +/- 0.1 microM, respectively) between children with PCD and healthy subjects. These findings suggest that NO synthase activity may not be decreased as much as might be expected on the basis of low exhaled and nasal NO levels.


Geographic Variation in Organ Size in a Toad (Duttaphrynus melanostictus).
Adaptive evolution is the process by which organisms change their morphological, physiological and biochemical characteristics to adapt to different environments during long-term natural selection. Especially, researching variation in organ size can provide important insights into morphological adaptation in amphibians. In this study, we comparatively studied differences in organ sizes (heart, lungs, liver, gallbladder, kidneys, spleen, digestive tract, testes and brain) among five geographical populations of the Asian common toad Duttaphrynus melanostictus. Our results revealed significant variations in the size of these nine specific organs among the populations. Notably, we observed a significant positive correlation between the relative size of the testes and latitude and/or altitude. However, no correlation was found between the relative size of the heart and the length of the digestive tract with altitude across populations, respectively, contradicting Hesse's rule and the digestion theory. These findings suggest that our study does not provide substantial theoretical support for the adaptive evolution of organ size in this particular toad species, but rather contributes to the understanding of the evolution and adaptations of species' different environmental conditions. Further research is warranted to delve deeper into the factors influencing organ size in amphibian populations.


Utilizing FBR to produce olefins from CO reduction using Fe-Mn nanoparticles on reduced graphene oxide catalysts and comparing the performance with SBR.
Mn was used as a promoter for Fe nanoparticles (NPs) loaded on reduced graphene oxide (rGO). The prepared catalysts were the unpromoted Fe/rGO catalysts along with two Mn promoted catalysts FeMn16 and FeMn29. These catalysts were used as Fischer-Tropsch catalysts in a Fixed Bed Reactor (FBR). The operating conditions of the reactor, namely temperature, pressure and space velocity, were varied to evaluate the catalyst performance and the olefin productivity. The olefins were produced in maximum yields of 34.5% and 31.3% with FeMn29 at 320 and 340 °C respectively. The ratio of light to heavy olefins was three times higher at 340 °C. The catalysts showed good stability up to 50 h of interrupted operation while varying the conditions at each interruption. The performance of the catalysts in the FBR was compared with a previous investigation carried out in an SBR under identical conditions with the same catalysts. The FBR was found to be more Mn tolerant than the SBR, giving very high conversion activity with high Mn concentrations (FeMn29). The FBR produced olefins in much higher yields than the SBR. The SBR was more selective to light olefins at low temperatures and high Mn loading levels, while the FBR produced light olefins at higher selectivities at high temperatures and high Mn concentrations.


The spectrum of radiological findings in H syndrome.
To describe the spectrum of radiological findings in 12 patients with H syndrome. Various radiological examinations of 12 patients (M=9, F=3) with H syndrome were reviewed. Symmetrical thickening of the skin of the subcutaneous tissue at the lower half of the body (n=9, 75%), with retracted micropenis in males (n=5, 55%). Groin varices (n=5, 42%) and lymphadenopathy (n=5, 42%) were observed in severe cases. Severe symmetrical flexion deformities of the fingers (n=7, 58%) were relatively common. Skin thickening with subcutaneous fat infiltration and deformities of the hands and feet are typical for H syndrome.


Epidemiology of brain tumors.
Brain tumors seemed to have increased in incidence over the past 30 years, but the rise probably results from use of new neuroimaging techniques. Treatments have not improved prognosis for rapidly fatal brain tumors. Established brain tumor risk factors (exposure to ionizing radiation, rare mutations of penetrant genes, and familial history) explain only a small proportion of brain tumors, and only one of these potentially is modifiable. Genetic and environmental characteristics likely play a role in familial aggregation of glioma and these factors are not identified. New concepts in brain tumor etiology and clinical management are the goal of research, with an aim at eradicating this devastating disease.


Kinetic modeling of aerobic biodegradation of high oil and grease rendering wastewater.
Batch scale activated sludge kinetic studies were undertaken for the treatment of pet food wastewater characterized by oil and grease concentrations of up to 21,500 mg/L, COD and BOD concentrations of 75,000 and 60,000 mg/L, respectively as well as effluent from the batch dissolved air flotation (DAF) system. The conducted kinetics studies showed that Haldane Model fit the substrates and biomass data better than Monod model in DAF-pretreated wastewater, while the modified hydrolysis Monod model better fit the raw wastewater kinetic data. For the DAF pretreated batches, Haldane Model kinetic coefficients k, K(S), Y and Ki values of 1.28-5.35 g COD/g VSS-d, 17,833-23,477 mg/L, 0.13-0.41 mg VSS/mg COD and 48,168 mg/L, respectively were obtained reflecting the slow biodegradation rate. Modified hydrolysis Monod model kinetic constants for the raw wastewater i.e., k, K(S), Y, and K(H) varied from 1-1.3 g COD/g VSS-d, 5580-5600 mg COD/l, 0.08-0.85 mg VSS/mg COD, and 0.21-0.66 d(-1), respectively.


Molecular characterization of antigen B2 subunit in two genotypes of Echinococcus granulosus from Indian bubaline isolates, its stage specific expression and serological evaluation.
Echinococcus granulosus is a parasitic helminth which affects both man and animals. During infection with larval stage of the organism secretory and membrane-bound (S/M) proteins play a meaningful role for evasion of immune system. Antigen B (AgB) is one of them. Present investigation has defined sequence diversity of AgB2 subunit of cattle and buffalo isolates of the organism. A total of 55 isolates were screened by polymerase chain reaction based single stranded conformation polymorphism (PCR-SSCP). Subsequently, six conformers could be detected. Based on predicted amino acid sequences of 90 amino acid residues, three clusters could be deduced. Sequence information of two buffalo isolates was homologous to AgB4 indicating gene switching phenomenon in between closely related isoforms. Numerical value of Tajima's D test proved negative selection pressure. Using artificial neural network (ANN), B cell linear epitope and stretches of agretope were predicted. Three clusters could be defined on the basis of B cell linear epitope. Out of three clusters, two showed more than 50% binding propensity with same MHCII alleles whereas, cluster 3 exhibited binding propensity with other MHCII alleles (DRB1_1501, DRB1_1502). Relative expression of AgB2 was more in active cysts (1.636 ± 0.092) followed by degenerating (0.449 ± 0.037) and calcified (0.255 ± 0.008). This result suggested that relative expression of AgB2 declines with progression of the disease. Using recombinant AgB2 sensitivity, specificity and accuracy of the ELISA test was 96.7, 94.7 and 95.9%, respectively. No cross reactivity was found with common cestode and trematode infected cattle and buffalo because cross reactive antigen was expressed intracellularly. Finally, this was concluded that AgB2 is the suitable immunological marker for detection, diagnosis and progression of the disease.


Electrocardiographic diagnosis of left ventricular hypertrophy by the time-voltage integral of the QRS complex.
This study was conducted to test the hypothesis that the time-voltage integral of the QRS complex can improve the electrocardiographic (ECG) identification of left ventricular hypertrophy. Standard ECG criteria have exhibited poor sensitivity for left ventricular hypertrophy at acceptable levels of specificity. However, left ventricular mass may be more closely related to the time-voltage integral of the summed left ventricular dipole than to QRS duration or voltages used in standard ECG criteria. Standard 12-lead ECGs, orthogonal lead signal-averaged ECGs and echocardiograms were obtained in 62 male control subjects without left ventricular hypertrophy and 51 men with left ventricular hypertrophy defined by echocardiographic criteria (indexed left ventricular mass > 125 g/m2). Voltage of the QRS complex was integrated over the total QRS duration in leads X, Y and Z to calculate the time-voltage integral of each orthogonal lead, of the maximal spatial vector complex and of the horizontal, frontal and sagittal plane vector complexes. At matched specificity of 99%, the 73% (37 of 51) sensitivity of the time-voltage integral of the vector QRS complex in the horizontal plane was significantly greater than the 10% sensitivity of the Romhilt-Estes point score, the 16% sensitivity of QRS duration alone, the 22% sensitivity of Cornell voltage, the 33% sensitivity of the 12-lead sum of QRS voltage and the 37% sensitivity of Sokolow-Lyon voltage (each p < 0.001). Sensitivity of the horizontal plane time-voltage integral was also greater than the 10% to 51% sensitivity of the time-voltage integral calculated in the individual X, Y or Z leads (p < 0.01 to < 0.001), the 18% and 35% sensitivity of the time-voltage integrals of the frontal and sagittal plane vectors (p < 0.001) and the 49% sensitivity of the time-voltage integral of the maximal spatial vector complex calculated from all three orthogonal leads (p < 0.001). Comparison of receiver operating characteristic curves confirmed that the superior performance of the horizontal plane time-voltage integral relative to standard and other signal-averaged criteria was independent of partition value selection. These findings suggest that use of the time-voltage integral of the QRS complex, a method that can be readily implemented on commercially available computerized ECG systems, can improve the accuracy of ECG methods for the identification of left ventricular hypertrophy.


Capacity-building for African American mental health training and research: lessons from the Howard-Dartmouth Collaborative summer school.
Many psychiatric residents have traditionally received little-or-no training in cross cultural approaches to psychiatric training and research. The Dartmouth-Howard Collaboration summer school training program had a 5-year grant to explore approaches to enhancing understanding of cultural factors in mental health treatment and research. Participants' questionnaire rating responses indicated that their experience in the Summer School program enhanced their understanding and experience in dealing with minority, largely African American patients and the diverse factors that affect their treatment. The Dartmouth-Howard Collaboration provides a model for a feasible training program that imparts knowledge regarding culture and mental health, and the conduct of mental health research, with particular attention to African American mental health. The program is unique in that it offers an intense, 1-week course delivered to several types of mental health professionals and trainees in research and practice.


Quantifying Fear Avoidance Behaviors in People With Concussion: A COSMIN-Informed Systematic Review.
OBJECTIVE: The validity of existing fear avoidance behavior patient-reported outcome measures (PROMs) for concussion is unknown. This study aims to (1) identify PROMs that assess fear avoidance behavior in individuals with concussion and (2) assess the measurement properties of these PROMs. DESIGN: A systematic review of outcome measurement instruments using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. LITERATURE SEARCH: We performed a systematic search of 7 databases. STUDY SELECTION CRITERIA: Studies were included if they assessed fear avoidance behavior (eg, kinesiophobia or cogniphobia) in participants with concussion, occurring in all settings (eg, sport, falls, assaults). DATA SYNTHESIS: Methodological quality of the PROMs was assessed using the COSMIN checklist, and the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: We identified 40 studies assessing fear avoidance. Four studies (n = 875 participants, representing 3 PROMs) were eligible for COSMIN assessment. Content validity for all PROMs was insufficient due to extreme risk of bias. The Fear Avoidance Short Form Scale demonstrated the greatest validity: moderate-certainty evidence for sufficient structural validity and internal consistency, and low-certainty evidence for measurement invariance. CONCLUSION: Current PROMs for measuring fear avoidance behaviors in people with concussion have insufficient content validity and should be used with caution in research and clinical practice. J Orthop Sports Phys Ther 2023;53(9):540-565. Epub: 10 August 2023. doi:10.2519/jospt.2023.11685.


Identification of mutated cyclization sequences that permit efficient replication of West Nile virus genomes: use in safer propagation of a novel vaccine candidate.
Existing live-attenuated flavivirus vaccines (LAV) could be improved by reducing their potential to recombine with naturally circulating viruses in the field. Since the highly conserved cyclization sequences (CS) found in the termini of flavivirus genomes must be complementary to each other to support genome replication, we set out to identify paired mutant CS that could support the efficient replication of LAV but would be unable to support replication in recombinant viruses harboring one wild-type (WT) CS. By systematic evaluation of paired mutated CS encoded in West Nile virus (WNV) replicons, we identified variants having single and double mutations in the 5'- and 3'-CS components that could support genome replication at WT levels. Replicons containing only the double-mutated CS in the 5' or the 3' ends of the genome were incapable of replication, indicating that mutated CS could be useful for constructing safer LAV. Despite the identity of the central portion of the CS in all mosquito-borne flaviviruses, viruses carrying complementary the double mutations in both the 5'- and the 3'-CS were indistinguishable from WT WNV in their replication in insect and mammalian cell lines. In addition to the utility of our novel CS pair in constructing safer LAV, we demonstrated that introduction of these mutated CS into one component of a recently described two-component genome system (A. V. Shustov, P. W. Mason, and I. Frolov, J. Virol. 81:11737-11748, 2007) enabled us to engineer a safer single-cycle WNV vaccine candidate with reduced potential for recombination during its propagation.


A health behaviour pandemic: The COVID-19 pandemic has impacted the physical activity, sleep, and sedentary behaviour of already-struggling Canadians.
The Canadian 24-Hour Movement Guidelines (24HMG) provide evidence-based recommendations for health behaviours, including light physical activity, moderate-to-vigorous physical activity (MVPA), sedentary behaviour (SB), sleep, and muscle strengthening activities. These behaviours likely changed as a result of public health measures implemented throughout the COVID-19 pandemic. We aimed to understand how Canadians' health behaviours changed during the pandemic. We conducted a nationwide survey asking Canadians aged 18-64 to report their health behaviours according to the 24HMG at three timepoints: 1) immediately prior to the pandemic, 2) the most restricted timepoint of the pandemic, and 3) more recently, in March 2022. We received 494 eligible responses from across Canada. Prior to the pandemic, only 7.7% of respondents were able to meet all 24HMG, which reduced to 3.8% during the most restricted phase of the pandemic (p < 0.01). During this timepoint, self-reported MVPA decreased by -21.9 ± 55.6 weekly minutes, muscle strengthening decreased by -0.34 ± 0.94 weekly sessions, and SB increased by 0.88 ± 2.04 daily hours (p < 0.00001 for all), with nonsignificant increases in nightly sleep. At the more recent March 2022 timepoint, mild recoveries were observed in all health behaviours, however remained significantly lower than baseline levels, with the exception of sleep, which decreased significantly (-0.18 ± 1.42 nightly hours, p = 0.005). Unfavourable health behaviour changes among Canadians were observed throughout the COVID-19 pandemic, which increases the risk for acute and long-term health conditions. Improved education, infrastructure, and support from public and private sectors can reverse the negative risk factors that arise from these health behaviour changes, and can improve the culture of proactive health behaviours in Canada.


Perioperative Nephrectomy Outcomes for Patients with Liver Disease: Implications for Liver Transplant Candidates.
To improve the management of cirrhotic patients diagnosed with new renal masses, we used a nationally representative cohort to assess the perioperative outcomes of nephrectomy in the setting of liver disease. The incidences of liver disease and renal masses are both rising in the US. Delaying liver transplantation to address other health concerns may have life changing consequences in these patients, thus these results help to guide treatment decisions at this critical junction in care. A retrospective study of the 2016-2019 Nationwide Readmissions Database was performed in adults undergoing nephrectomy for non-emergent indications. Outcomes were compared between 3 cohorts: no chronic liver disease (no CLD), chronic liver disease (CLD), and decompensated cirrhosis (DC). Mixed regression models were used to evaluate the association between CLD and DC with outcomes of interest including morbidity, mortality, readmission rates, non-home discharges, length of stay, and costs. A total of 183,362 patients were evaluated. The mortality rate in the DC cohort (7%) was higher than with CLD (0.4%) and no CLD (0.3%), (P <.001). DC was associated with higher mortality (OR 8.29, 95% CI 4.07 - 16.88), postoperative bleeding requiring transfusion (OR 5.55, 95% CI 3.72 - 8.26), non-home discharge (OR 5.12, 95% CI 3.16 - 8.30) and readmission (OR 1.79, 95% CI 1.09 - 2.94) compared to no CLD. The DC cohort had the greatest length of stay and costs. Patients undergoing nephrectomy with DC have increased morbidity, mortality, readmission rates, non-home discharges, LOS and costs. Alternative management strategies may be considered in these patients.


Myeloid-derived suppressor cells shift Th17/Treg ratio and promote systemic lupus erythematosus progression through arginase-1/miR-322-5p/TGF-β pathway.
Immune cells play important roles in systemic lupus erythematosus (SLE). We previously found that myeloid-derived suppressor cell (MDSC)-derived arginase-1 (Arg-1) promoted Th17 cell differentiation in SLE. In the present study, we performed RNA-chip to identify the microRNA regulation network between MDSCs and Th17 cells. miR-542-5p in humans, as the homologous gene of miR-322-5p in mice was significantly up-regulated in the Th17+MDSC group compared with Th17 cells cultured alone and down-regulated in the Th17+MDSC+Arg-1 inhibitor group compared with the Th17+MDSC group. We further evaluated the miR-322-5p and Th17/Treg balance in mice and found that the proportions of both Th17 cells and Tregs were elevated and that miR-322-5p overexpression activated the transforming growth factor-β pathway. Moreover, although miR-322-5p expression was higher in SLE mice, it decreased after treatment with an Arg-1 inhibitor. The proportion of Th17 cells and Th17/Treg ratio correlated with miR-322-5p levels. In conclusion, MDSC-derived Arg-1 and mmu-miR-322-5p not only promote Th17 cell and Treg differentiation, but also shift the Th17/Treg ratio in SLE. The Arg-1/miR-322-5p axis may serve as a novel treatment target for SLE.


The Use of a Brochure to Enable CAM-with-Chemotherapy Patient Education.
The majority of cancer patients receiving chemotherapy will consider taking complementary and alternative medicine (CAM) during their treatment. As biologically-active CAM may detrimentally interfere with chemotherapy treatment, cancer patients require evidence-based information on chemotherapy-CAM integration consequences. This study aimed to assess if the availability of a purpose-designed brochure within a cancer service aided doctors' discussions with their patients on CAM use and helped patients understand the effects of CAM during their chemotherapy treatment. Cancer care doctors consulting in an adult day unit completed a structured post-intervention feedback survey form (n = 17), and cancer patients receiving chemotherapy treatment were provided the brochure and completed the local health service consumer testing feedback form (n = 30). All cancer care doctors perceived a need for the brochure and recommended the brochure to their patients. All doctors thought the brochure made it easier for them to discuss CAM with their patients, and 59 % believed that it saved them time during patient consultations. Ninety percent of cancer patients reported the brochure had enough information to answer their CAM questions, and all patients thought the information was easy to read and understand. An evidence-based CAM-with-chemotherapy patient brochure was perceived to have enabled cancer care doctors to discuss CAM with their patients and to have answered patients' CAM questions.


Organizational and individual conditions associated with depressive symptoms among nursing home residents over time.
To examine the effect of organizational culture and climate on depressive symptoms among nursing home residents. Using a pooled cross-sectional design, this study examines a sample of 23 nursing homes, 1,114 employees, and 5,497 residents. Depressive symptoms were measured using the Minimum Data Set, Depression Rating Scale. Organizational culture and climate were measured using the Organizational Social Context Scale. Data were analyzed using hierarchical linear modeling. Depressive symptoms were associated with 2 dimensions of organizational culture (proficiency and resistance), 3 dimensions of climate (stress, engagement, and functionality), geographic location, facility size, staffing ratios, and impairments in activities of daily living and cognition. Findings suggest that values and beliefs that guide behavior in an organization and employees' perceived impact of the work environment of their well-being have a significant impact on resident mental health.


The relationship between meaning in life and post-traumatic stress symptoms in US military personnel: A meta-analysis.
Subjective meaning in life has been theorized to play a critical role in the adjustment to traumatic events. However, its association with post-traumatic stress symptoms has not been quantitatively reviewed. Informed by Park's integrated meaning-making model and evidenced-based psychological treatments for post-traumatic stress disorder, the goals of this meta-analysis were to: (1) to determine the direction and magnitude of the association between meaning in life and post-traumatic stress symptoms; and (2) to examine potential moderators of this association (i.e., age, sex, race, marital status, type of trauma, and meaning in life conceptualization). CINAHL, Embase, PILOT, PsycINFO, PubMed, and Web of Science core collection databases were searched. A random-effects meta-analysis was conducted on 26 associations (N = 9,751). A significant, moderate, negative relationship was found between meaning in life and post-traumatic stress symptoms (r = -0.41; 95% CI: -0.47 to -0.35, k = 25). No significant moderators were detected. Findings suggest that meaning in life plays a crucial role in adjustment to traumatic events. Development and testing of randomized controlled trials to determine whether increases in meaning in life result in reductions of post-traumatic stress in US military personnel may facilitate ongoing efforts aimed at recovery from trauma.


Antagonistic action between cyclic AMP and estrogen in phosphorylation of mammary tumor nuclear proteins.
A new protein kinase-dependent phosphorylation occurs in the nuclei of hormone-dependent, 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced mammary carcinoma following preincubation of tumor slices with cyclic adenosine 3',5'-monophosphate (cAMP). The presence of 17beta-estradiol in the medium inhibits this effect. Both events have been observed in vivo in the nuclei of DMBA-induced tumors. The phosphorylation pattern of nuclei in hormone-independent mammary tumor, DMBA No. 1, however, is not affected by preincubation with either cAMP or estrogen. These findings suggest that the antagonistic effect of cAMP and estrogen in the growth control of mammary tumors is exerted through a specific action on nuclear protein phosphorylation and that these events correlate with the hormone-dependency of the tumors.


Identification and validation of immune and prognosis-related genes in hepatocellular carcinoma: A review.
Bioinformatics methods were used to identify the key genes associated with the immune microenvironment of hepatocellular carcinoma (HCC) to construct an immune risk prognostic model (IRPM) and to study the correlation between IRPM's risk groups and immune characteristics of patients with HCC. HCC transcriptome sequencing information was searched for immune-related genes (IRGs) that were regularly expressed in cancer tissues. The IRGs, which were strongly linked to overall survival were screened; the prognostic characteristics model was constructed using Cox regression analysis. IRPM's independent prognostic value was explored; Kaplan-Meier survival and receiver-operating characteristic curves were used to determine the model prediction ability in the led-to queue. Patients in the high-risk group (HRG) showed significantly poor outcomes. Gene Set Enrichment Analysis revealed factors involved in both the HRG and low risk group. Immune-related hub genes (IRHGs) and drug sensitivity expression levels revealed that all IRHGs were correlated with drug sensitivity for certain chemotherapy drugs. The study results may serve as a reference for improving prognosis, early screening, and immunotherapy in patients with HCC.


Memory formation for an appetitive visual discrimination task in young chicks.
The three-phase model of memory formation in young chicks proposed by Gibbs and Ng [7] was based on a single trial passive avoidance task. Some methodological and interpretative problems associated with this task are not encountered in appetitive visual discrimination tasks. Using such a task, it is shown that 2 mM KCl induces amnesia at 10 min, ouabain at 30 min and cycloheximide at 60 min after learning. These findings are consistent with those for the single trail passive avoidance task and confirm the generality of a model of memory formation in young chicks entailing a short-term phase, a sodium pumo-dependent labile phase, and a long-term, protein synthesis-dependent phase.


Teaching behavioral medicine using individual coronary heart disease risk factors.
Two hundred twenty-one first-year medical students participated in a voluntary coronary heart disease risk factor self-change project designed to teach the principles of behavioral change. Blood pressure, serum lipids, percentage body fat, cardiovascular fitness, and smoking status were measured prior to the project. Students designed their own programs of behavior modification and, after 8 weeks, repeat measurements were obtained in students whose projects related to coronary heart disease risk (56% of entire group). Despite generally low initial coronary heart disease risk factors, most risk factor groups successfully altered the targeted risk factors. The subgroup attempting to lower serum cholesterol (n = 49) reduced total cholesterol 15 +/- 24 mg/dl (mean +/- SD) and low-density lipoprotein cholesterol 11 +/- 20 mg/dl (P less than 0.001 for both). The blood pressure group (n = 9) decreased systolic blood pressure 8 +/- 10 mm Hg (P less than 0.05), and the weight-loss group (n = 33) lost 3.0 +/- 2.9 kg (P less than 0.001), reducing estimated percentage body fat 1.7 +/- 1.8 (P less than 0.001). The self-change project was well received by the students and appears to be a useful technique for introducing the principles of behavioral medicine to first-year medical students.


Gastrin induces histamine release from human cutaneous mast cells.
Physiologic concentrations of human gastrin I (G17) and a synthetic analog of the carboxy-terminal region of gastrin, pentagastrin, provoked a dose-related release of histamine from human cutaneous mast cells in vitro. The N-terminal tridecapeptide portion of gastrin (G1-13) neither stimulated histamine release nor blocked the action of G17. In vivo correlation studies demonstrated that low concentrations (10(-12)M to 10(-10)M) of G17 or pentagastrin administered intradermally provoked a modest but definite wheal-and-flare response in four out of six normal subjects and a more marked, dose-related response in a patient with mastocytosis. These results indicate that physiologic concentrations of gastrin can stimulate mediator release from human cutaneous mast cells. We propose that this response may be mediated through receptors recognizing the carboxy-terminal region of the gastrin molecule. The possible role of gastrin-induced human mast cell-mediator release should be considered in the assessment of allergic disorders and in experimental models investigating mast cell function.


[Heterogeneity of murine sarcoma cells for transplantability due to their different susceptibilities to the lytic action of macrophages].
Sarcoma was induced in C57BL/6 mice with 20-methylcholanthrene. The sarcoma cells were found to be heterogeneous in their transplantability. The study of 9 clones distinct in this property has shown that heterogeneous transplantability was due to different susceptibility to lytic action of macrophages.


Weight-control approaches: a review by the California Dietetic Association.
Weight reduction is considered a therapeutic success if weight loss is maintained with no expense to overall health. The California Dietetic Association, a professional organization including 5,000 registered dietitians, proposes, on the basis of a review of the current scientific literature, the following criteria for health-safety evaluation of dietary approaches. A weight-reduction diet should (a) satisfy all nutrient needs except energy, (b) meet individual tastes and habits, (c) minimize hunger and fatigue, (d) be readily obtainable and socially acceptable, (e) favor the establishment of a changed eating pattern, and (f) be conducive to improvement of overall health. Characteristics of diet approaches associated with poor outcome include (a) very-low-calorie diets, which promote rapid weight loss, (b) extremes of macronutrient restriction, and (c) reliance on formula diets or special products. The use of diets, surgery, drugs, exercise, and behavior modification is discussed.


The Issues of Freedom and Happiness in Moral Bioenhancement: Continuing the Debate With a Reply to Harris Wiseman.
During the previous years, Harris Wiseman has devoted substantial attention to my stance on voluntary moral bioenhancement. He argued that he has been influenced by that position, but nonetheless criticized it. I haven't replied to his criticisms yet and wish to do so now. One of the reasons is to avoid my position being misrepresented. By replying to Wiseman's criticisms, I also wish to clarify those issues in my standpoint that might have given rise to some of the misinterpretations. With the same purpose in mind, I will demarcate my concept of voluntary moral bioenhancement from related standpoints, in particular from Persson and Savulescu's notion of compulsory moral bioenhancement that, as I argued, diminishes our freedom (of the will). Furthermore, I will consider the possibility of adding another essential element to my position-one that I have not discussed in my earlier publications. It is designed to propose a novel explanation of why humans would be motivated to opt for voluntary moral bioenhancement if its outcome is not a lowering of the likelihood of "Ultimate Harm" (as defined by Persson and Savulescu) or a milder form of self-destruction of humanity. This explanation will be based on the conception that an increase in happiness, rather than Ultimate Harm prevention, might be the grounding rationale for moral bioenhancement.


Studies on the pathogenesis of swine dysentery. II. Search for a cytotoxin in spirochetal broth cultures and colon content.
Broth cultures of Treponema hyodysenteriae and colonic content from pigs with swine dysentery were tested for cytotoxicity in cell cultures, erythrocyte suspensions and in ligated segments of pig colon. Live cells of T. hyodysenteriae attached to the surface of cells in all cultures tested but did not penetrate them nor cause morphologic change detectable by light microscopy. Only live T. hyodysenteriae caused erythrolysis. Broth cultures or colonic content sterilized by filtration or by disruption with ultrasound had no visible effect on the cell cultures, erythrocyte suspensions or the mucosa of ligated colonic segments.


Preparation of reactive sintering Si3N4-Si2N2O composites ceramics with diamond-wire saw powder waste as raw material.
In this paper, the reactive sintering Si3N4-Si2N2O composites ceramics were fabricated from the diamond-wire saw powder through the reaction-sintering nitridation method. The effects of sintering temperatures, holding time and oxygen contents on the Si3N4-Si2N2O composites formation were investigated in detail. The results revealed that the phases of final products consisted of α/β-Si3N4 and Si2N2O, and the proportion of three phases could be influenced by sintering temperatures and oxygen contents. In addition, rod-like particles and clastic granules were observed in final specimens, and rod-like particles mainly formed in low sintering temperatures and low oxygen contents, which could be attributed to the vapor-vapor-solid (VVS) growth mechanism. Furthermore, a lot of rod-like particles were distributed in cracks among the Si3N4-Si2N2O composites matrixes, which formed the bridge structures and enhanced the mechanical properties. The specimen obtained at 1500 ℃ with 5 wt.% SiO2 in raw materials had the highest compression strength of 150.6 MPa and the highest flexural strength of 46.1 MPa. Comparing with other typical composites, the Si3N4-Si2N2O composites in this work showed the desirable mechanical properties. Thus, this study provided an environment-friendly approach to recycle photovoltaic waste and reduce the cost of the reactive sintering Si3N4-Si2N2O composites ceramics.


Association of chemokine expression in anterior cruciate ligament deficient knee with patient characteristics: Implications for post-traumatic osteoarthritis.
Stromal cell-derived factor-1a (SDF-1α) and high mobility group box chromosomal protein 1 (HMGB1) are chemokines that can drive post-traumatic osteoarthritis (PTOA) induced by anterior cruciate ligament (ACL) injury. However, the influence of patient characteristics on expression of those chemokines remains unclear. Our aim was to determine the relationship between chemokine expression in synovial fluid (SF) of the ACL-deficient (ACL-D) knee and patient characteristics including time from injury, sex, and age. SF samples were collected immediately prior to the first-time ACL reconstruction (ACLR) from 82 patients. Expression of SDF-1α and HMGB1 was measured with human-specific solid phase sandwich enzyme-linked immunosorbent assays. The expression levels between groups divided by time from injury, or age, or sex was compared using Student's t-test. The association of SDF-1α or HMGB1 levels with those variables was determined using regression analysis and Pearson product-moment correlation coefficient. Regression and correlation analysis indicated significant correlation between SDF-1α expression and time from injury in the cohort (r = -0.266, P = 0.016, n = 82) and in females (r = -0.386, P = 0.024, n = 34). Significant correlation was also observed between SDF-1α expression and age in the cohort (r = -0.224, P = 0.043, n = 82) and in males (r = -0.289, P = 0.046, n = 48). No significant correlation between HMGB1 expression and patient characteristics was detected. SDF-1α rather than HMGB1 might serve as a protein marker for monitoring the development of PTOA in the ACL-D knee, especially in female patients.


Can being scared cause tummy aches? Naive theories, ambiguous evidence, and preschoolers' causal inferences.
Causal learning requires integrating constraints provided by domain-specific theories with domain-general statistical learning. In order to investigate the interaction between these factors, the authors presented preschoolers with stories pitting their existing theories against statistical evidence. Each child heard 2 stories in which 2 candidate causes co-occurred with an effect. Evidence was presented in the form: AB?E; CA?E; AD?E; and so forth. In 1 story, all variables came from the same domain; in the other, the recurring candidate cause, A, came from a different domain (A was a psychological cause of a biological effect). After receiving this statistical evidence, children were asked to identify the cause of the effect on a new trial. Consistent with the predictions of a Bayesian model, all children were more likely to identify A as the cause within domains than across domains. Whereas 3.5-year-olds learned only from the within-domain evidence, 4- and 5-year-olds learned from the cross-domain evidence and were able to transfer their new expectations about psychosomatic causality to a novel task.


Association and Clinical Outcomes of Marijuana in Patients with Intracerebral Hemorrhage.
An epidemiological relationship between intracerebral hemorrhage (ICH) and marijuana use is not known. Data about the impact of marijuana on ICH patient's outcomes remain scarce. The Nationwide Inpatient Sample was investigated from 2004 to 2011 to identify cohorts with marijuana (N = 2,496,165) and nonmarijuana (N = 116,163,454) usage. Patients with a primary diagnosis of ICH were identified using International Classification of Diseases, Ninth Edition, Clinical Modification codes. Univariable analysis was used to compare demographics and risk factors for ICH, and to study patient outcomes in ICH patients with or without marijuana use. Binary logistic regression analyses were used to study marijuana as independent predictor of ICH and to assess its effect on patient outcomes. The prevalence of ICH was greater in the marijuana cohort (relative risk: 1.11, confidence interval [CI]: 1.07-1.16). However, marijuana use (odds ratio [OR]: 1.063; CI: .963-1.173) was not an independent predictor of ICH after adjusting for other illicit drug use and ICH risk factors. For in-hospital outcomes, marijuana users had fewer adverse discharge dispositions (OR .78; CI: .72-.86), reduced length of hospitalization (OR .54; CI: .48-.61), and lower hospitalization cost (OR .72; CI: .64-.81) but higher in-hospital mortality (OR 1.26; CI: 1.12-1.41). Marijuana users are more likely to be admitted with ICH, however, marijuana is not an independent risk factor for ICH. Although marijuana has paradoxical effect on ICH related outcomes, higher mortality rates in marijuana users offset any potential protective effect among ICH patients.


Isolation and initial characterization of residual nuclear structures from yeast.
Residual nuclear structures have previously been isolated from a wide range of eukaryotic organisms. When nuclei are isolated from Saccharomyces cerevisiae and then treated with 1.95 M NaCl and DNase I, sedimentable residual structures are obtained similar in several respects to structures isolated from organisms previously studied. These yeast residual nuclear structures retain less than 7% of nuclear DNA, less than 17% of nuclear RNA and less than 50% of nuclear proteins. Electron microscopy suggests that these structures are derived from the nuclear interior and are composed of a sparse fibrogranular network. Replicating DNA is preferentially bound to these yeast residual nuclear structures, just as it is to residual nuclear structures from other organisms.


Altered neurotransmitter expression profile in the ganglionic bowel in Hirschsprung's disease.
Despite having optimal pull-through (PT) surgery for Hirschsprung's disease (HSCR), many patients experience persistent bowel symptoms with no mechanical/histopathological cause. Murine models of HSCR suggest that expression of key neurotransmitters is unbalanced proximal to the aganglionic colonic segment. We aimed to investigate expression of key enteric neurotransmitters in the colon of children with HSCR. Full-length PT specimens were collected fresh from children with HSCR (n=10). Control specimens were collected at colostomy closure from children with anorectal malformation (n=8). The distributions of neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), and substance P (SP) were evaluated using immunofluorescence and confocal microscopy. Neurotransmitter quantification was with Western blot analysis. ChAT expression was high in aganglionic bowel and transition zone but reduced in ganglionic bowel in HSCR relative to controls. Conversely, nNOS expression was markedly reduced in aganglionic bowel but high in ganglionic bowel in HSCR relative to controls. VIP expression was similar in ganglionic HSCR and control colon. SP expression was similar in all tissue types. Imbalance of key excitatory and inhibitory neurotransmitters in the ganglionic bowel in HSCR may explain the basis of bowel dysmotility after an optimal pull-through operation in some patients.


Toxins in mussels (Mytilus galloprovincialis) associated with diarrhetic shellfish poisoning episodes in China.
More than 200 people in China suffered illness with symptoms of diarrhetic shellfish poisoning (DSP) following consumption of mussels (Mytilus galloprovincialis). The event occurred in the cities of Ningbo and Ningde near the East China Sea in May, 2011. LC-MS/MS analysis showed that high concentrations of okadaic acid, dinophysistoxin-1, and their acyl esters were responsible for the incidents. The total concentration was more than 40 times the EU regulatory limit of 160 μg OA eq./kg. Pectentoxin-2 and its seco-acids were also present in the mussels. Additionally, yessotoxins were found to be responsible for positive mouse bioassay results on scallop (Patinopecten yessoensis) and oyster (Crassostrea talienwhanensis) samples collected from the North Yellow Sea in June, 2010. This work shows that high levels of lipophilic toxins can accumulate in shellfish from the Chinese coast and it emphasises that adequate chemical analytical methodologies are needed for monitoring purposes. Further research is required to broaden the knowledge on the occurrence of lipophilic toxins in Chinese shellfish.


Adenine nucleotide levels and regional distribution of ATP in rabbit spinal cord after ischemia and recirculation.
Rabbit spinal cords were subjected to 10 to 40 minutes of ischemia with and without 4 days of recirculation and L-4 segment was analyzed for adenylates and ATP-induced bioluminiscence. ATP level and energy charge was progressively reduced by increasing durations of ischemia. Regional evaluation of ATP-induced bioluminiscence after 10 and 20 minutes of ischemia revealed ATP depletion mainly in the gray matter of spinal cord. Forty minutes of ischemia resulted in complete reduction of ATP bioluminiscence in both gray and white matter. Within 4 days of recirculation following all periods of ischemia studied, only partial metabolic recovery occurred. Restitution of ATP-induced bioluminiscence was regionally heterogeneous, reduced predominantly in the anterior horns of gray matter.


High-grade endometrial stromal sarcoma with YWHAE-NUTM2B fusion gene abnormality identified after 10 years of recurrent pulmonary metastases: A case report.
•Endometrial stromal sarcoma is the second most common type of uterine sarcoma.•Endometrial stromal sarcoma has undergone modifications since its proposal.•This case highlights the importance of accurately diagnosing endometrial stromal sarcoma.•Asymptomatic uterine fibroids may not be treated with therapeutic intervention or prompt regular check-ups.


Antimicrobial peptide LL-37 attenuates infection of hepatitis C virus.
Although recent studies indicate that supplementation with vitamin D (VD) potentiates a sustained viral response by interferon-based therapy to chronic hepatitis C, detailed mechanisms are not fully defined. The production of cathelicidin, an antimicrobial peptide, has been demonstrated to be part of the VD-dependent antimicrobial pathway in innate immunity. Cathelicidin is known to directly kill or inhibit the growth of microbial pathogens including mycobacteria and viruses. We used a hepatitis C virus (HCV) cell culture system to clarify the anti-HCV effects of the human cathelicidin, LL-37. HuH-7 cells were administrated with LL-37 and infected with cell culture-generated HCV (HCVcc). HCV propagation was estimated by measuring the level of HCV core antigen (Ag). Treatment with LL-37 resulted in decreased intra- and extracellular levels of HCV core Ag, suggesting inhibition of HCV propagation. To assess the effects of LL-37 on HCV replication, JFH-1 subgenomic replicon RNA-transfected cells were treated with LL-37. However, inhibition of HCV replication was not detected by this assay. To clarify the effects on HCV infection, we treated HCVcc with LL-37 and removed the antimicrobial peptide prior to use of the virus in infection. This exposure of HCVcc to LL-37 diminished the infectivity titers in a dose-dependent fashion. Iodixanol density gradient analysis revealed that the peak fraction of infectivity titer was eliminated by LL-37 treatment. The VD-associated antimicrobial peptide LL-37 attenuated the infectivity of HCV. This anti-HCV effect of LL-37 may explain the contribution of VD to the improved efficacy of interferon-based therapy.


A phenylpropanoid glycoside with antioxidant activity from Picria tel-ferae.
A phytochemical study on Picria tel-ferae resulted in the isolation of a phenylpropanoid glycoside (1), which was reported for the first time from this plant. The structure of compound 1 was identified as 1-O-3,4-(dihydroxyphenyl)- ethyl-beta-D- apiofuranosyl- (1-->4)-alpha-L-rharmnopyranosyl- (1-->3)-4-O-caffeoyl- beta-D-glucopyranoside on the basis of spectroscopic analyses. In addition, it was found that 1 exhibited a remarkable inhibitory effect on lipid peroxidation initiated by either a free radical [AAPH; 2,2'-azobis-(2-amidinopropane)dihydrochloride] or generated hydroxyl radical (Fe2+/ascorbate). These findings, together with those of previous studies, suggest that P. tel-ferae possesses abundant phenylpropanoid glycosides, and the plant might be used beneficially in the treatment of oxidative stress-related human diseases.


[Sequence analysis and expression of GRA7 gene of Toxoplasma gondii isolates in Escherichia coli].
To analyze the difference of GRA7 gene of Toxoplasma gondii different isolated strains and express GRA7 in Escherichia coli. The GRA7 gene was amplified from genomes of T. gondii isolates by PCR and was cloned into pGEX-4T-1. The recombinant plasmid was transformed into JM109 and sent to be sequenced. The sequence was analyzed with CLUSTALW (an internet tool). The recombinant plasmid was induced by IPTG to express the fusion protein,which was identified by SDS-PAGE and Western blot with positive sera. The protein was purified and used as a diagnostic antigen for ELISA to test serum samples. There was no difference among the sequences of T. gondii GRA7 gene from different isolates. The recombinant plasmid pGEX-4T-1/GRA7 induced by IPTG was expressed in E. coli. It was a GST fusion protein and could react with human and rabbit positive sera analyzed by Western blot. The GRA7 gene of T. gondii isolates is highly conservative. The GRA7 is expressed as a recombinant protein in Escherichia coli, which shows an immunoreactivity.


Interactions between Passive and Active Vibrations in the Organ of Corti In Vitro.
High sensitivity and selectivity of hearing require an active cochlea. The cochlear sensory epithelium, the organ of Corti, vibrates because of external and internal excitations. The external stimulation is acoustic pressures mediated by the scala fluids, whereas the internal excitation is generated by a type of sensory receptor cells (the outer hair cells) in response to the acoustic vibrations. The outer hair cells are cellular actuators that are responsible for cochlear amplification. The organ of Corti is highly structured for transmitting vibrations originating from acoustic pressure and active outer hair cell force to the inner hair cells that synapse on afferent nerves. Understanding how the organ of Corti vibrates because of acoustic pressure and outer hair cell force is critical for explaining cochlear function. In this study, cochleae were freshly isolated from young gerbils. The organ of Corti in the excised cochlea was subjected to mechanical and electrical stimulation that are analogous to acoustic and cellular stimulation in the natural cochlea. Organ of Corti vibrations, including those of individual outer hair cells, were measured using optical coherence tomography. Respective vibration patterns due to mechanical and electrical stimulation were characterized. Interactions between the two vibration patterns were investigated by applying the two forms of stimulation simultaneously. Our results show that the interactions could be either constructive or destructive, which implies that the outer hair cells can either amplify or reduce vibrations in the organ of Corti. We discuss a potential consequence of the two interaction modes for cochlear frequency tuning.


Association of attention-deficit/hyperactivity disorder with diabetes: a population-based study.
Cognitive impairment has been documented in adult diabetes but is unclear in pediatric diabetes. No study had been conducted to explore the relationship between attention-deficit/hyperactivity disorder (ADHD) and diabetes. Using a population-based data set, we aimed to examine the association between ADHD and a prior diagnosis of diabetes mellitus (DM) in Taiwan. A total of 4,302 patients with ADHD were selected as cases and 21,510 randomly selected subjects as controls. We used conditional logistic regression to calculate the odds ratio (OR) for having previously received a diagnosis of DM between subjects with and without ADHD. In this study, 116 of the 25,812 sampled subjects (0.5%) had received a diagnosis of DM prior to their index date. Subjects with ADHD had a higher proportion of prior DM diagnoses than controls (0.9% vs. 0.4%, P < 0.001). After adjusting for age, sex, index year, geographic location, and obesity, ADHD was significantly associated with a prior diagnosis of type 2 DM (OR = 2.75, 95% confidence interval (CI) = 1.82-4.16). However, no significant association was observed between ADHD and type 1 DM. The findings suggest that ADHD was associated with a previous diagnosis of type 2 DM.


Effective plasma concentrations of aprindine in canine ventricular arrhythmias.
Antiarrhythmic effects of aprindine were examined using three canine ventricular arrhythmia models (induced by digitalis, adrenaline, and two-stage coronary ligation), and the minimum effective plasma concentration of aprindine was determined for each arrhythmia model. Aprindine suppressed all three arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by digitalis, adrenaline, and 24-h and 48-h coronary ligation were 0.8 +/- 0.4, 1.0 +/- 0.4, 1.6 +/- 0.3, and 3.1 +/- 0.5 micrograms/ml, respectively (mean +/- SD, n = 6-7). The minimum effective plasma concentrations of aprindine for digitalis- and adrenaline-induced arrhythmias were significantly lower than those for coronary ligation-induced arrhythmias. Oral aprindine was also effective in suppressing both the 24- and 48-h coronary ligation-induced arrhythmias. Aprindine had a hypotensive effect when it was given intravenously, but this effect was not observed when it was given orally. The correlations between the aprindine plasma concentrations and the antiarrhythmic effects were not very strong and indicated individual variations in sensitivity to aprindine.


Connectome to behaviour: modelling Caenorhabditis elegans at cellular resolution.
It has been 30 years since the 'mind of the worm' was published in Philosophical Transactions B (White et al 1986 Phil. Trans. R. Soc. Lond. B314, 1-340). Predicting Caenorhabditis elegans' behaviour from its wiring diagram has been an enduring challenge since then. This special theme issue of Philosophical Transactions B combines research from neuroscientists, physicists, mathematicians and engineers to discuss advances in neural activity imaging, behaviour quantification and multiscale simulations, and how they are bringing the goal of whole-animal modelling at cellular resolution within reach.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.


Intraoperative Observational Real-time Electrocochleography as a Predictor of Hearing Loss After Cochlear Implantation: 3 and 12 Month Outcomes.
A decrease in intracochlear electrocochleographic (ECochG) amplitude during cochlear implantation has been associated with poorer postoperative hearing preservation in several short-term studies. Here, we relate the stability of ECochG during surgery to hearing preservation at 3- and 12-months. Patients with hearing ≤80-dB HL at 500 Hz were implanted with a slim-straight electrode array. ECochG responses to short, high-intensity, 500-Hz pure tones of alternating polarity were recorded continuously from the apical-most electrode during implantation. No feedback was provided to the surgeon. ECochG amplitude was derived from the difference response, and implantations classified by the presence ("ECochG drop") or absence ("no drop") of a ≥30% reduction in ECochG amplitude during insertion. Residual hearing (relative and absolute) was reported against the ECochG class. ECochG was recorded from 109 patients. Of these, interpretable ECochG signals were recorded from 95. Sixty-six of 95 patients had an ECochG drop during implantation. Patients with an ECochG drop had poorer preoperative hearing above 1000 Hz. Hearing preservation (in decibels, relative to preoperative levels and functionally) was significantly poorer at 250-, 500-, and 1000-Hz at 3 months in patients exhibiting an ECochG drop. Twelve-month outcomes were available from 85 patients, with significantly poorer functional hearing, and greater relative and absolute hearing loss from 250 to 1000 Hz, when an ECochG drop had been encountered. Patients exhibiting ECochG drops during implantation had significantly poorer hearing preservation 12 months later. These observational outcomes support the future development of surgical interventions responsive to real-time intracochlear ECochG. Early intervention to an ECochG drop could potentially lead to prolonged improvements in hearing preservation.


Targeting the Immune Complex-Bound Complement C3d Ligand as a Novel Therapy for Lupus.
Humoral autoimmunity is central to the development of systemic lupus erythematosus (SLE). Complement receptor type 2 (CR2)/CD21 plays a key role in the development of high-affinity Abs and long-lasting memory to foreign Ags. When CR2 is bound by its primary C3 activation fragment-derived ligand, designated C3d, it coassociates with CD19 on B cells to amplify BCR signaling. C3d and CR2 also mediate immune complex binding to follicular dendritic cells. As the development of SLE involves subversion of normal B cell tolerance checkpoints, one might expect that CR2 ligation by C3d-bound immune complexes would promote development of SLE. However, prior studies in murine models of SLE using gene-targeted Cr2-/- mice, which lack both CR2 and complement receptor 1 (CR1), have demonstrated contradictory results. As a new approach, we developed a highly specific mouse anti-mouse C3d mAb that blocks its interaction with CR2. With this novel tool, we show that disruption of the critical C3d-CR2 ligand-receptor binding step alone substantially ameliorates autoimmunity and renal disease in the MRL/lpr model of SLE.


A novel electron paramagnetic resonance signal of "oxygenated" cytochrome c oxidase.
It had been observed previously that a pair of transient EPR resonances (g = 1.78 and 1.69) appears within less than 5 ms on reoxidation of reduced cytochrome c oxidase by O2. Since the location of other lines that are part of the same signal was not known, the quantity of the paramagnetic species involved, and thus the significance of the observed resonances, remained questionable. We have now found a broad resonance at g = 5 which is obviously associated with those at g = 1.78 and 1.69. The width of the signal (approximately 250 mT) at the observed intensity suggests that it represents a significant fraction of one of the components of the enzyme. The signal disappears within less than 5 ms on addition of cyanide or sulfide but only within several hundred milliseconds after addition of ferrocytochrome c. This behavior suggests that it originates from the a3 component of the enzyme. It is suggested that the species represented in the signal is either identical with or part of what has been named collectively the "oxygenated" form and recently described "activated" forms of the enzyme. On reoxidation of reduced oxidase with oxygen enriched 90% in 17O, no change of signal shape was seen.


Laser-induced thrombus formation and vascular reactivity in the microcirculation of the spontaneously hypertensive rat.
Thrombi formation resulting from laser-induced injury to mesenteric circulation has been studied in spontaneously hypertensive (SH) and normotensive rats. The thrombotic reaction was enhanced in both venules and arterioles of the SH rats. In the arterioles of the hypertensive rats, the vasoconstriction which develops downstream from the thrombus is greatly intensified and the time to form microvascular haemostatic plugs significantly decreased in the arterioles of these animals. These phenomena have been explained on the basis of an increased reactivity of the vascular smooth muscle of the SH rats to vasoconstrictor substances liberated from platelets at the site of injury.


Intrinsic characteristics of Cr⁶⁺-resistant bacteria isolated from an electroplating industry polluted soils for plant growth-promoting activities.
The Cr(6+)-resistant plant growth-promoting bacteria was isolated from soil samples that were collected from an electroplating industry at Coimbatore, India, that had tolerated chromium concentrations up to 500 mg Cr(6+)/L in Luria-Bertani medium. Based on morphology, physiology, and biochemical characteristics, the strain was identified as Bacillus sp. following the Bergey's manual of determinative bacteriology. Evaluation of plant growth-promoting parameters has revealed the intrinsic ability of the strain for the production of indole-3-acetic acid (IAA), siderophore, and solubilization of insoluble phosphate. Bacillus sp. have utilized tryptophan as a precursor for their growth and produced IAA (122 μg/mL). Bacillus sp. also exhibited the production of siderophore that was tested qualitatively using Chrome Azurol S (CAS) assay solution and utilized the insoluble tricalcium phosphate as the sole source of phosphate exhibiting higher rate of phosphate solubilization after 72 h of incubation (1.45 μg/mL). Extent of Cr(6+) uptake and accumulation of Cr(6+) in the cell wall of Bacillus sp. was investigated using atomic absorption spectrophotometer and scanning electron microscope-energy dispersive spectroscopy, respectively. The congenital capability of this Cr(6+)-resistant plant growth-promoting Bacillus sp. could be employed as bacterial inoculum for the improvement of phytoremediation in heavy metal contaminated soils.


Corrigendum: A Pilot Study on the Cutoff Value of Related Brain Metabolite in Chinese Elderly Patients With Mild Cognitive Impairment Using MRS.
[This corrects the article DOI: 10.3389/fnagi.2021.617611.].


Differential inhibition of signaling pathways by two new imidazo-pyrazoles molecules in fMLF-OMe- and IL8-stimulated human neutrophil.
N-formyl-methionyl-leucyl-phenylalanine (fMLF), its methyl ester fMLF-OMe and interleukin 8 (IL8) play a pivotal role in neutrophil chemotaxis regulation in the latter and early stages, respectively, but the mechanisms through which the signal transduction pathways activate this function are not yet completely understood. Compounds 3l and 3r, a new class of arylcarbamoyl-imidazo-pyrazoles derivatives, were described as the first example of compounds able to inhibit human neutrophil chemotaxis induced by both fMLF-OMe and IL8. Here, we report their effects on superoxide production and lysozyme release. No inhibition was observed, thus they could be defined as "pure" chemotactic antagonists. Therefore, such molecules were used to highlight specific kinases involved in neutrophil chemotaxis. Our data provide support that compounds 3l and 3r strongly inhibit p38 MAPK with either fMLF-OMe or IL8 chemoattractants, while they show different signaling pathways regarding PKC isoforms suggesting that a fine tuning of the neutrophil activation occurs through differences in the activation of signaling pathways. Neither fMLF-OMe nor IL8 were able to obtain activation of the PI3K/Akt pathway. Since anomalous activation of neutrophil recruitment is one of the causes of many inflammatory diseases, the good versatility of our derivatives could represent the most important characteristic of these new molecules in the development of novel therapeutics.


Detection of Excitatory and Inhibitory Synapses in the Auditory System Using Fluorescence Immunohistochemistry and High-Resolution Fluorescence Microscopy.
In sensory systems, a balanced excitatory and inhibitory circuit along the ascending pathway is not only important for the establishment of topographically ordered connections from the periphery to the cortex but also for temporal precision of signal processing. The accomplishment of spatial and temporal cortical resolution in the central nervous system is a process that is likely initiated by the first sensory experiences that drive a period of increased intracortical inhibition. In the auditory system, the time of first sensory experience is also the period in which a reorganization of cochlear efferent and afferent fibers occurs leading to the mature innervation of inner and outer hair cells. This mature hair cell innervation is the basis of accurate sound processing along the ascending pathway up to the auditory cortex. We describe here, a protocol for detecting excitatory and inhibitory marker proteins along the ascending auditory pathway, which could be a useful tool for detecting changes in auditory signal processing during various forms of hearing disorders. Our protocol uses fluorescence immunohistochemistry in combination with high-resolution fluorescence microscopy in cochlear and brain tissue.


Evidence for a spectral basis of texture perception in bat sonar.
Bats obtain information about the structure of objects in the outside world from their echolocation signals, an extremely useful method when hunting non-flying prey in densely cluttered habitats, for example. Information about object structure is contained both in the time and in the spectral interference patterns of signals reflected from surfaces at different distances from the bat. I report here an experiment designed to test the extent to which bats use these two types of information. A 'phantom target' is generated by playing back to an echolocating bat signals that mimic the result of reflection from two planes set at different distances. The ability of the bat to discriminate between two such targets is investigated as a function of the separations of the planes. Several of the results do not fit the hypothesis that the bat simply uses time-delay information: the very small time difference that can be discriminated, the fall off in ability to discriminate planes at a particular separation and the symmetry of the discrimination ability measured in the frequency domain. The empirical data can best be fitted by a function based on spectral correlation.


Use-dependent facilitation of L-like Ca2+ channels counteracts GABAB-mediated inhibition of N-like Ca2+ channels in rat sensory neurons.
Baclofen selectively blocked the inactivating N-like component of the high voltage-activated Ca2+ current (HVA-ICa) without affecting the sustained L-like component of the HVA-ICa in rat sensory neurons. The inhibition of the N-like component by baclofen was reversed by a large depolarizing prepulse to +50 mV as a result of facilitation of the L-like component. These results might indicate that a decrease in influx of Ca2+ through N-like Ca2+ channels due to the baclofen-induced block or due to the voltage-dependent inactivation induced by the depolarizing prepulse can be partially compensated by a rapid Ca2+ influx through extra L-like component facilitated by the depolarizing prepulse. Such a compensation of the Ca2+ influx by the use-dependent facilitation of L-like component may be a significant mechanism for adaptive regulation of Ca2+ channels in response to stimulation with a wide range of amplitude and frequency.


Symptoms in the first two years of life. A preliminary population study of infantile autism.
A population sample of autistic children (n = 26) were compared retrospectively with age- and sex-matched mentally retarded children (n = 20) and age- and sex-matched population-representative children (n = 25) on a 130-item questionnaire to the mother concerning characteristic features of the child's behaviour in the first 2 years of life. Thirteen items discriminated clearly between the groups. The results are discussed in the context of early screening for autism.


A study of feasibility of dose reduction in paediatric MSCT scanning with a constant image quality.
The aim of the work relies on the adjustment of scanning parameters, kV and mAs, in multislice computed tomography (MSCT) to reduce paediatric patient dose whilst keeping the same reference image quality. Only abdomen examinations are employed in this study. The measurement of noise in a region of interest (ROI) inside the liver in a reference adult man has been chosen as an image quality parameter. Paediatric patients are categorised according to the width and thickness of abdomen trunk. A relationship between patient size, image quality and dose reduction has been obtained. The study has been performed at the Meyer Children Hospital (1300 CT paediatric patient/year).


Recurrence of posterior uveal melanoma after 60Co episcleral plaque therapy.
The authors analyzed the clinical and follow-up data on 277 selected patients with primary choroidal or ciliochoroidal melanoma who were treated with 60Co plaque radiotherapy between 1976 and 1982. Local recurrence of the irradiated melanoma developed in 39 (14%) patients during the follow-up interval. The 5-year tumor recurrence rate (Kaplan-Meier) was estimated to be 12%. Multivariate prognostic factor analysis (Cox proportional hazards modeling) identified the largest linear tumor dimension and proximity of the posterior margin of the tumor to the optic nerve head as predictors of recurrence. The 5-year survival rate of patients whose tumors recurred (58%) was significantly (log-rank test P = 0.0023) worse than that of patients whose tumor remained clinically controlled (82%).


Dipyridamole in the treatment of angina pectoris: a meta-analysis.
A meta-analysis was performed to reevaluate the efficacy of dipyridamole for prophylaxis of angina pectoris. We found 10 articles that reported 11 randomized control trials published between 1960 and 1970. Three trials found a statistically significant benefit for the drug vs placebo, four showed a positive trend, two found no difference, and two showed a slight trend favoring placebo. When the results of all 11 trials were combined, two different statistical methods showed a statistically significant benefit from the drug. These combined results must be interpreted cautiously because of excluded patients and other methodologic variations in the studies, as well as evidence from other studies that dipyridamole may aggravate angina. Nevertheless, we conclude that there is some evidence for efficacy of the drug and believe the question should be restudied in larger and better-designed trials.


The quadriceps angle: reliability and accuracy in a fox (Vulpes vulpes) pelvic limb model.
To evaluate the effect of measurement technique and limb positioning on quadriceps (Q) angle measurement, intra- and interobserver reliability, potential sources of error, and the effect of Q angle variation. Cadaveric radiographic study and computer modeling. Pelvic limbs from red foxes (Vulpes vulpes). Q angles were measured on hip dysplasia (HD) and whole limb (WL) view radiographs of each limb between the acetabular rim, mid-point (Q1: patellar center, Q2: femoral trochlea), and tibial tuberosity. Errors of 0.5-2.0 mm at measurement landmarks alone and in combination were modeled to identify the effect on Q angle. The effect of measured Q angles on the medial force exerted on the patella (F(MEDIAL)) was calculated. The HD position yielded significantly (P < .001) more medial Q angles than the WL position. No significant difference was observed between Q1 and Q2, but Bland-Altman plots indicated they were not equivalent. Intra- and interobserver agreement was substantial. Q2 errors were inherently greater than Q1: the mid-point and tibial tuberosity are the most important sources of Q angle variability. Increasing Q angles significantly increased the exerted F(MEDIAL) (P < .0001, gradient 1.7%). Measurements are reliable, but Q2 is more prone to error than Q1, and the 2 measurement techniques are not interchangeable. Positional errors must be kept below 1.3 mm (Q1) or 0.8 mm (Q2).


Integrating geospatial and ground geophysical information as guidelines for groundwater potential zones in hard rock terrains of south India.
The increasing demand of water has brought tremendous pressure on groundwater resources in the regions were groundwater is prime source of water. The objective of this study was to explore groundwater potential zones in Maheshwaram watershed of Andhra Pradesh, India with semi-arid climatic condition and hard rock granitic terrain. GIS-based modelling was used to integrate remote sensing and geophysical data to delineate groundwater potential zones. In the present study, Indian Remote Sensing RESOURCESAT-1, Linear Imaging Self-Scanner (LISS-4) digital data, ASTER digital elevation model and vertical electrical sounding data along with other data sets were analysed to generate various thematic maps, viz., geomorphology, land use/land cover, geology, lineament density, soil, drainage density, slope, aquifer resistivity and aquifer thickness. Based on this integrated approach, the groundwater availability in the watershed was classified into four categories, viz. very good, good, moderate and poor. The results reveal that the modelling assessment method proposed in this study is an effective tool for deciphering groundwater potential zones for proper planning and management of groundwater resources in diverse hydrogeological terrains.


Hypoadiponectinemia is closely associated with impaired nitric oxide synthase activity in skeletal muscle of type 2 diabetic subjects.
In vitro studies suggest that adiponectin plays an important role in nitric oxide (NO) generation. We studied the relationship between plasma adiponectin and skeletal muscle nitric oxide synthase (NOS) activity in type 2 diabetic (T2DM) patients. We determined NOS activity in skeletal muscle of 7 T2DM and 8 nondiabetic control subjects under basal conditions and after a 4-h euglycemic insulin (80 mU/m2 x min) clamp. Insulin-stimulated glucose disposal (Rd) (5.2 +/-0.4 vs. 9.0 +/-0.9 mg/kg-min, P < 0.01) and basal NOS activity (107 +/-45 vs. 459 +/- 100 pmol/min-mg protein, P < 0.05) were reduced in T2DM versus controls. In response to hyperinsulinemia, NOS activity increased approximately two-fold in controls (757 +/- 244, P < 0.05 vs basal) but failed to increase in T2DM (105 +/- 38, P < 0.01 vs. T2DM). Basal NOS protein content was similar in controls and T2DM and did not change following insulin. Plasma adiponectin was decreased in T2DM (4.5 +/- 0.8 vs. 7.0 +/-1.0 microg/mL, P < 0.02) and correlated with insulin-stimulated NOS activity (r = 0.49, P < 0.05) and with Rd (r = 0.50, P < 0.05). In controls and T2DM collectively, Rd correlated with insulin-stimulated NOS activity (r = 0.48, P < 0.05). Decreased plasma adiponectin correlates with impaired insulin-stimulated NOS activity and severity of insulin resistance in T2DM. Because impaired NO generation plays a central role in endothelial dysfunction and development of atherosclerosis, our results may provide a link between reduced plasma adiponectin levels and accelerated atherosclerosis in T2DM.


Effect of soluble complement receptor-1 on neutrophil accumulation after traumatic brain injury in rats.
As part of the acute inflammatory response, neutrophils accumulate in the central nervous system after injury. Recently, a soluble human recombinant complement receptor (sCR1; BRL 55730; T Cell Sciences, Inc., Cambridge, MA, U.S.A.) has been developed that inhibits the activation of both the classical and the alternative pathways of complement. sCR1 attenuates the effects of the acute inflammatory response in several models of injury outside the central nervous system. The role of complement in traumatic brain injury, however, remains undefined. We hypothesized that treatment with sCR1 would attenuate neutrophil accumulation in the brain after cerebral trauma. Using a randomized, blinded protocol, 18 anesthetized Sprague-Dawley rats were pre-treated with sCR1 or saline (control) at both 2 h and 2 min before trauma (weight drop) to the exposed right parietal cortex. A third dose of sCR1 (or saline) was given 6 h after trauma. Coronal brain sections centered on the site of trauma were obtained at 24 h after trauma and analyzed for myeloperoxidase (MPO) activity as a marker of neutrophil accumulation. Complete blood counts with differential were obtained before treatment with sCR1 and at 24 h after trauma. At 24 h after trauma, brain MPO activity was reduced by 41% in sCR1-treated rats compared with control rats [0.1599 +/- 0.102 versus 0.2712 +/- 0.178 U/g (mean +/- SD); p = 0.02]. The neutrophil count in peripheral blood increased approximately twofold in both groups. Neutrophil accumulation occurring in the brain after trauma is inhibited by sCR1 treatment. This suggests that complement activation is involved in the local inflammatory response to traumatic brain injury and plays an important role in neutrophil accumulation in the injured brain.


Multivariable evaluation of maternal hemodynamic profile in pregnancy complicated by fetal growth restriction: prospective study.
To evaluate the association between fetal growth restriction (FGR) and maternal hemodynamic parameters using multivariable analysis, adjusting for major confounding factors, such as hypertensive disorders of pregnancy (pre-eclampsia and gestational hypertension). A prospective cohort study was conducted between January 2013 and April 2016. Two cohorts of patients were recruited, between 24 and 39 weeks of gestation, in a high-risk outpatient setting. These cohorts comprised 49 appropriate-for-gestational-age singleton fetuses and 93 that were FGR (abdominal circumference (AC) at recruitment in the second half of pregnancy ≤ 10th percentile with a previous normal AC at 20-22 weeks). Maternal echocardiography was performed at the time of enrolment and included hemodynamic parameters of systolic and diastolic function and cardiac remodeling indices. Data were analyzed using a multivariable generalized linear model to estimate the association of FGR with maternal hemodynamic parameters after adjusting for significant confounding factors. In the multivariable analysis, after adjustment for hypertensive disorders of pregnancy and smoking, FGR was associated with a 14% increase in maternal total vascular resistance, 16% reduction in cardiac output, 13% reduction in left ventricular mass and 11% reduction in heart rate; similar results were observed for the corresponding indexed parameters. Hypertensive disorders of pregnancy in the absence of FGR were associated with a 25% increase in total vascular resistance, 16% increase in left ventricular mass and 14% reduction in diastolic function; similar results were observed for the corresponding indexed parameters. FGR is significantly and independently associated with several maternal hemodynamic parameters, even after adjustment for major confounding factors, such as hypertensive disorders of pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.