Ribosomal gene amplification in multinucleate oocytes of the egg brooding hylid frog Flectonotus pygmaeus.
The multinucleate oocytes of Flectonotus pygmaeus begin as cysts containing 2,000 or more meiotic nuclei. Each nucleus amplifies its ribosomal DNA early in oogenesis. The level of amplification is widely different from one nucleus to another, and ranges from less than 0.1 x C to more than 8 x C. The C value for this species is 1.7 x 10(-12) g of DNA. In oocytes of about 0.5 mm diameter the nuclei sort themselves out into an outer shell of several hundred nuclei that swell up to become much larger than the nuclei that remain in the inner compact mass. Later the outer nuclei continue to swell and decrease in number while the inner nuclei disintegrate and disappear. By the time the oocyte reaches. 1.2 mm diameter there are only a few large nuclei left and each has many large nucleoli and a full set of lampbrush chromosomes. Eventually, only one germinal vesicle nucleus is left, and this has all the characteristics of the single germinal vesicles that are typical of oocytes from other amphibians. It is suggested that the sorting out of nuclei into the inner mass and the outer shell of larger nuclei in middle sized oocytes is a consequence of the positions the nuclei happen to be in at the time, but that the "contest" for the role of germinal vesicle may be won by the nucleus of the outer shell that has the highest ribosomal DNA content.


Concurrent validity of the Warner Initial Developmental Evaluation of Adaptive and Functional Skills and the Bayley Scales of Infant and Toddler Development, Third Edition.
To determine the concurrent validity of the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS), a criterion-specified questionnaire that assesses a child's adaptive skills in everyday contexts, and the Bayley Infant and Toddler Scales of Development, Third Edition (Bayley-III). In a prospective cohort study, 431 WIDEA-FS and Bayley-III assessments were completed among 341 children, aged 10 to 36 months corrected age (158 females, 183 males; median [interquartile range] gestational age at birth 32wks [29-38]), monitored in a high-risk neonatal intensive care unit follow-up clinic. WIDEA-FS scores were significantly associated with Bayley-III scores in all domains. Lower scores on the WIDEA-FS were significantly associated with an increased risk of adverse developmental performance on all Bayley-III scales. The association was strongest for motor and language Bayley-III scores when tested at <30 months of age, and for cognitive Bayley-III scores when tested at ≥30 months of age. The WIDEA-FS has concurrent validity with the Bayley-III and may be a useful tool in high-risk follow-up settings. WIDEA-FS mobility, communication, and social cognition domains are concurrently valid in infants at high-risk for neurodevelopmental disability. Bayley-III motor, language, and cognitive composite scores are concurrently valid in the same group. The WIDEA-FS mobility and communication domains may be most clinically useful in children <30 months.


[L-DOPA interaction with the brain tissue DNA of rats].
The possibility of direct interaction of L-DOPA with DNA isolated from rat brain tissue has been considered. The spectral and viscosity data suggest conformational changes in L-DOPA-treated DNA in conditions excluding the accumulation of L-DOPA oxidation products.


Microbiological and clinical profile of infective endocarditis patients: an observational study experience from tertiary care center Karachi Pakistan.
The study analyzed microbiological and antimicrobial susceptibility profile of organisms isolated from patients with infective endocarditis (2015-17) and compared disease outcomes in cohorts of endocarditis patient with history of prior invasive vascular intervention (high risk group) vs those without (native valve group). We hypothesized that high risk group would be more likely to have severe disease outcomes. This was a prospective cohort study (2015-17). All blood and cardiac tissue samples of enrolled patients suspected of endocarditis according to modified Duke's criteria were followed for microbiological and antimicrobial susceptibility profile. The high risk group was compared with the native valve group with 90 day follow up to determine difference in clinical course and outcome in terms of disease severity (defined as any patient with endocarditis undergoing surgical management, readmission or dying). The data was analyzed using SPSS 21.0 software and chi-square test. 90 day mortality was calculated using Kaplan Meier survival curves. Total 104 patients with endocarditis were enrolled. Overall culture positivity rate was 71.2%. Streptococcus species were the most common isolate (36.7%), followed by S. aureus (17.3%) cases. In Streptococcus species, 14.2% showed intermediate susceptibility to penicillin. Thirty six patients were included in the cohort analysis. A poor outcome was seen in 85.7% high risk group as compared to 50% of native valve group. The overall mortality rate was 19.4%. We found Streptococcus species to be the predominant pathogen for endocarditis overall. However Staphylococcus aureus predominated native valve group. High risk group showed more complicated clinical course.


Change in lung function and morbidity from chronic obstructive pulmonary disease in alpha1-antitrypsin MZ heterozygotes: A longitudinal study of the general population.
A deteriorating effect of severe alpha(1)-antitrypsin deficiency (ZZ genotype) on lung function is well known, whereas the role of intermediate deficiency (MZ genotype) remains uncertain. To test the hypothesis that MZ intermediate alpha(1)-antitrypsin deficiency affects pulmonary function and disease. Population-based cohort study with 21-year follow-up. Copenhagen, Denmark. 9187 adults randomly selected from the Danish general population. Plasma alpha(1)-antitrypsin levels, annual decrease in FEV(1), airway obstruction, and hospitalization and mortality from chronic obstructive pulmonary disease (COPD). 451 participants (4.9%) carried the MZ genotype. Plasma alpha(1)-antitrypsin levels were 31% lower in MZ heterozygotes than in persons with the MM genotype (Student t -test, P < 0.001). Annual decrease in FEV(1) was 25 mL in MZ heterozygotes and 21 mL in persons with the MM genotype (t -test, P = 0.048). Airway obstruction was found in 19% of MZ heterozygotes compared with 15% of MM carriers (chi-square test, P = 0.023); in a logistic regression analysis adjusted for age, sex, and tobacco consumption, the corresponding odds ratio was 1.3 (CI, 1.0 to 1.7). The incidence of hospitalization and mortality from COPD was 32 cases per 10 000 person-years in persons with the MZ genotype and 22 cases per 10 000 person-years in those with the MM genotype (log-rank test, P = 0.063). In a Cox regression model adjusted for age, sex, tobacco use, and FEV(1) at study entry, relative risk for COPD outcomes in persons with the MZ genotype versus persons with the MM genotype was 1.5 (CI, 1.0 to 2.3). All these results were independent of the S and E alleles in this gene and were not affected by cystic fibrosis Delta F508 heterozygosity. MZ heterozygotes had a slightly greater rate of decrease in FEV(1) and were modestly over-represented among persons with airway obstruction and COPD. In the population at large, MZ heterozygosity may account for a fraction of COPD cases---on the order of 2%, similar to the percentage of persons with COPD who have the severe but rare ZZ genotype.


5'-AMP aminohydrolase activity in erythrocytes from normal and dystrophic individuals.
5'-AMP aminohydrolase activities in red blood cells from normal human adults and from patients with pseudohypertrophic dystrophy, myotonic dystrophy, limb girdle dystrophy, neuromuscular atrophy, Charcot-Marie Tooth Disease, and spinal muscular atrophy were examined. In contrast to the greatly decreased skeletal muscular levels of 5'-AMP aminohydrolase observed in Pseudohypertrophic muscular dystrophy, levels in red blood cells of all patients were not significantly different from normals. Pyruvate kinase and creatine kinase activities were determined for comparative purposes. The density distribution of normal and dystrophic erythrocytes were essentially identical.


CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention in Diverse Clinical Settings.
Background Studies have demonstrated increased risk of major atherothrombotic events in CYP2C19 loss-of-function (LOF) variant carriers versus non-carriers treated with clopidogrel after percutaneous coronary intervention (PCI). We sought to evaluate real-world outcomes with the clinical implementation of CYP2C19-guided antiplatelet therapy after PCI. Methods and Results Data from 9 medical centers where genotyping was performed in the setting of PCI were included. Alternative therapy with prasugrel or ticagrelor was recommended for patients with a CYP2C19 LOF variant. The primary outcome was the composite of major atherothrombotic events (all-cause death, myocardial infarction, ischemic stroke, stent thrombosis, or hospitalization for unstable angina) within 12 months following PCI. Moderate or severe/life-threatening bleeding within 12 months was a secondary outcome. Among 3342 patients, 1032 (31%) were LOF carriers, of whom 571/1032 (55%) were treated with alternative therapy. In LOF carriers, the rate of major atherothrombotic events was lower in patients treated with alternative therapy versus clopidogrel (adjusted HR, 0.56; 95% CI 0.39-0.82). In those without a LOF allele, no difference was observed (adjusted HR, 1.07; 95% CI 0.71-1.60). There was no difference in bleeding with alternative therapy versus clopidogrel in either LOF carriers or those without a LOF allele. Conclusions Real-world data demonstrate lower atherothrombotic risk in CYP2C19 LOF carriers treated with alternative therapy versus clopidogrel and similar risk in those without a LOF allele treated with clopidogrel or alternative therapy. These data suggest that PCI patients treated with clopidogrel should undergo genotyping so that CYP2C19 LOF carriers can be identified and treated with alternative therapy.


Platelet dysfunction contributes to the haemostatic defect in haemorrhagic fever with renal syndrome.
To characterize further the nature of haemostatic impairment in haemorrhagic fever with renal syndrome, we assessed platelet function in 9 patients in whom the diagnosis was serologically confirmed. Defective platelet aggregation was demonstrated in every patient. An abnormality of the granule release reaction was demonstrated in all of 7 patients tested. Gel-filtered platelets from a normal subject showed normal aggregation in plasma from a patient with impaired aggregation, which is evidence for an intrinsic platelet defect, and against the presence of a circulating inhibitor in this patient.


Liver accumulation of 2,3,7,8-tetrachloro-[3H]dibenzofuran in mice: modulation by treatments with polychlorinated biphenyls.
The distribution of 2,3,7,8-tetrachloro-[3H]dibenzofuran ([3H]TCDF; 40 micrograms/kg) resembled that earlier reported for 2,3,7,8-tetrachlorodibenzo-p-dioxin, with a strong accumulation in the liver and a selective uptake in the nasal olfactory mucosa of adult and fetal mice. Pretreatments with a series of selected congeners of polychlorinated biphenyls (PCBs), i.e.. I (IUPAC)-77, I-105, I-118, I-126, I-153, I-156, I-169, and a commercial preparation, Aroclor 1254 (25-100 mg/kg body wt. i.p.), were found to modulate the hepatic uptake of [3H]TCDF (24 h post-3H-injection). At a short pretreatment time (4 h), non-ortho-chlorinated congeners decreased the uptake of [3H]TCDF equivalents in the liver (e.g., I-126 = 3,3',4,4',5-pentachlorobiphenyl: 34% of control), while several mono- and di-ortho PCB congeners and Aroclor 1254 increased the hepatic uptake of [3H]TCDF (e.g., I-156 = 2,3,3',4,4',5-hexachlorobiphenyl: 183% of control). At a longer pretreatment time (48 h), both a non-ortho (I-169 = 3,3',4,4',5,5'-hexachlorobiphenyl) and mono-ortho PCB congener(s) (e.g. I-156) markedly increased the hepatic 3H-uptake (190%), a probable effect of an induction of hepatic binding sites for TCDF. Ethoxyresorufin-O-deethylase activities, regarded to mirror the metabolic activity of cytochrome P-450 IA1 (CYP IA1), were strongly and time-dependently induced after I-169, but not after I-156, pretreatment (25 mg/kg). The initial liver concentrations of the two PCB congeners were similar and increased for I-169 but not for I-156 at later time points. In conclusion, the results show a selective uptake of [3H]TCDF in the mouse liver and nasal olfactory mucosa of both dam and fetus. The uptake of [3H]TCDF in the liver is influenced both by dose and pre-exposure with PCBs. The presence of a PCB-sensitive, but CYP IA1-independent, hepatic binding site for TCDF is suggested. Consequently, pharmacokinetic interactions with PCBs complicate the toxicity assessment of TCDF in complex mixtures.


PhRMA survey of pharmacogenomic and pharmacodynamic evaluations: what next?
Interindividual variation in pharmacodynamic (PD) response to drugs is an ongoing area of research for drugs in clinical development, pre- and postapproval. To characterize how pharmacogenomic (PG ) variations can serves a predictor of differences in PD outcomes, the pharmaceutical industry has incorporated PG /PD analysis into clinical drug development. The Pharmaceutical Research and Manufacturers of America (PhRMA ) and the Industry Pharmacogenomics Working Group (I-PWG) conducted a survey of 16 pharmaceutical companies to ascertain to what extent PG/PD research is being incorporated into drug development. The survey results showed that, while the industry has made some attempt to incorporate PG/PD studies into drug development, application has been inconsistent. Nevertheless, several valid PG/PD markers have since emerged in drug labels. The I-PWG considers PG/PD research an important approach to improving success rates in drug development. This article reports the results of the survey and proposes steps toward increasing the use of PG/PD research by the industry.


Effect of 10 weeks endurance training on the concentration of lipids and lipoproteins as well as on the composition of high-density lipoproteins in blood serum.
The effect of 10 weeks endurance training on the concentration of serum lipids and lipoproteins, particularly on the composition of high-density lipoproteins, was measured in nine 22--28-year-old male volunteers at weekly intervals during training as well as 5 and 10 weeks following the exercise program. A control group consisted of six male subjects between the ages of 22 and 37 years. The endurance program consisted of running for approximately 30 min three times a week covering about 5--7 km per session. Two participants discontinued the program after 6 weeks while the remaining seven completed the training in the course of 10 weeks. After the end of the exercise program, all subjects showed a 20%--25% decrease in free cholesterol as well as a 40% decrease in triglycerides while esterified cholesterol remained unchanged. Only in subjects with HDL cholesterol/total cholesterol ratios of less than 0.3 at the start of the exercise program was a statistically significant increase in HDL cholesterol values (P less than 0.05) following training observed. In all subjects HDL phosphatidyl choline values were elevated by a mean of 20% at the end. With the exception of two participants, the HDL triglyceride concentration was diminished after the exercise program. The concentrations of HDL apolipoprotein A-I and A-II were unaffected by exercise. In the control group, no statistically significant changes of the measured parameters could be observed. Our results suggest that short-term physical training produces changes in cholesterol ersterification and/or cholesterol-ester transport as well as in HDL composition.


Recurrent resemblance in potential topography at different instants during ventricular depolarization and repolarization. Normal conduction contrasted with left bundle branch block and paced beats.
During ventricular activation and recovery, potential distribution may be exquisitely reproduced on instantaneous maps separated in time by many milliseconds. The timing and duration of these periods of strong resemblance (absolute r = 0.80 over 142 thoracic reference sites) may provide useful insight into the underlying patterns of the spread of activation and resumption of the repolarized state. This study examined 80 normal volunteers, 35 patients with left bundle branch block (LBBB), and 41 patients with permanent pacemakers. Normal subjects showed three basic patterns of recurrent surface map resemblance: (1) positive correlation between maps in early QRS and those throughout ST-T, but with greatest focus in late ST-T; (2) negative correlation between maps in early QRS and late QRS; and (3) negative correlation between maps in late QRS and early ST-T. These findings may be hypothetically attributed to the retention or recreation of similar relationships between the anatomic distributions of resting versus active or plateau versus repolarizing cells on the endocardial and epicardial surfaces, respectively. On the other hand, patients with LBBB and pacemakers were distinctly different in the timing and frequency of sustained resemblances. In these two states, there was sustained or continuing resemblance (positive correlation) between successive maps throughout QRS and again between successive maps through ST-T. In addition, the surface map pattern found throughout ST-T consistently appeared as the negative correlate of the preceding pattern that had dominated QRS.


STMN-1 gene: a predictor of survival in stage iia esophageal squamous cell carcinoma after Ivor-Lewis esophagectomy?
Prognosis of esophageal squamous cell carcinoma (ESCC) is stage-specific; however, some patients with the same stage have different survival outcomes. Clinically, it is significant to explore the biological marker to predict patient's outcome. We investigated the association between the stathmin1 gene (STMN-1) expression and the prognosis of patients who underwent Ivor-Lewis esophagectomy. A total of 162 patients who suffered from midthoracic stage IIA ESCC and completely resected with Ivor-Lewis esophagectomy were studied for STMN-1 expression by qRT-PCR in fresh-frozen tissue and validated by immunohistochemistry in matched formalin fixed-paraffin embedded tissue samples. STMN-1 level was evaluated as a prognostic factor in ESCC. SPSS 21.0 software was used to analyze the relationship between STMN-1 expression and clinicopathological characteristics and survival probability. The overall 3- and 5-year survival was 72.20 and 42.00 % respectively. Ninety-four patients (58.02 %) experienced disease recurrence with a disease-free interval of 21.50 ± 1.20 months. qRT-PCR result showed that STMN-1 mRNA level in patients who were alive at the end of follow-up was lower compared with patients who died during the follow-up period (p < 0.05). Immunohistochemical results showed that 94 patients had STMN-1 protein overexpression (58.02 %), patient with STMN-1 overexpression had worse survival compared with patients who had low STMN-1 expression (p = 0.00). Cox regression analysis revealed that STMN-1 protein expression and T classification are independent prognostic factors. Even localized ESCC are potential to relapse with poor prognosis. This study demonstrates that STMN-1 level is an independent prognostic factor after Ivor-Lewis esophagectomy. In addition, assessment of STMN-1 level could improve stratification of stage IIA ESCC patients.


Biological therapy and dentistry: a review paper.
In recent years, a new class of drugs has revolutionized the treatment of autoimmune, allergic, infectious, and many more diseases. This new class of drugs is made of 3 groups-cytokines, monoclonal antibodies, and fusion proteins-that may target special damaged cells but not all the cells. These drugs may have side effects such as infection, hypersensitivity, hematologic disorders, cancer, hepatotoxicity, and neurologic disorders. However, there is not enough evidence or long-term studies of the mechanism of action and side effects of these drugs. Patients receiving biological therapies may need special consideration in dentistry. This paper is a review of the classification, mechanism of action, and side effects of these drugs and dental consideration for patients receiving biological therapies.


Solitary peribronchiolar metaplasia showing a sub-solid nodule on computed tomography.
Recent advances in radiographic imaging and thoracic surgery have facilitated surgery for small lung tumors by eliminating the need for pathological diagnosis. To date, we have experienced two cases of small lung tumors that were surgically resected without pathological diagnosis as malignant. Computed tomography (CT) revealed sub-solid nodules in the peripheral lung. After tumor resection, both tumors were pathologically diagnosed as peribronchiolar metaplasia. To the best of our knowledge, solitary peribronchiolar metaplasia showing a sub-solid nodule on CT imaging has not previously been reported.


Serum concentrations of vitamin E in healthy infants fed commercial milks.
Serum vitamin E concentrations were determined in 60 term and 26 premature infants during the first 2 months of life. All infants received commercial milk formula containing vitamin E. In addition, premature infants older than 10 days were given vitamin E orally as a multivitamin preparation. Thus, daily intake of vitamin E was nearly 1.2 mg/kg body weight in term infants and 2--3 mg/kg body weight in premature infants. In term infants serum levels of vitamin E rose from 2.6 mg/l (cord blood) to 7.0 mg/l (3rd--13th day) and 9.1 mg/l (16th--25th day) and remained at 10 mg/l (in the second month of life). Hemoglobin concentration and red cell number decreased continuously due to physiological anemia of infancy. In premature infants mean values of vitamin E were the same as in term infants. Vitamin E deficiency with hemolytic anemia could be demonstrated in a 2 months old infant suffering from cystic fibrosis.


Catalytic synthesis of new pyrazolo [3,4-b] pyridine via a cooperative vinylogous anomeric-based oxidation.
In this study, a novel nano-magnetic metal-organic frameworks based on Fe3O4 namely Fe3O4@MIL-101(Cr)-N(CH2PO3)2 was synthesized and fully characterized. The prepared sample was used as catalyst in the synthesis of pyrazolo [3,4-b] pyridines as convenient medicine by condensation reaction of aldehydes, 5-(1H-Indol-3-yl)- 2H-pyrazol-3-ylamine and 3-(cyanoacetyl)indole via a CVABO. The products were obtained with high yields at 100 °C and under solvent-free conditions.


A fluorescence histochemical method for the demonstration of central catecholamine neurons in young embryonic tissues.
A simple fluorescence histochemical technique is described for the production of catecholamine histofluorescence in the developing brain of rat embryos. The procedure combines the magnesium-formaldehyde-glutaraldehyde perfusion technique, with polyethylene glycol dehydration and embedding. Several examples illustrate the sensitivity of the technique and the good preservation of tissue sections. The tissue can also be stored for several weeks without an appreciable loss of fluorescence.


The MRI appearance of cystic lesions around the knee.
This review presents a comprehensive illustrated overview of the wide variety of cystic lesions around the knee. The aetiology, clinical presentation, MRI appearances and differential diagnosis are discussed. Bursae include those related to the patella as well as pes anserine, tibial collateral ligament, semimembranosus-tibial collateral ligament, iliotibial and fibular collateral ligament-biceps femoris. The anatomical extension, imaging features and clinical significance of meniscal cysts are illustrated. Review of ganglia includes intra-articular, extra-articular, intraosseous and periosteal ganglia, highlighting imaging findings and differential diagnoses. The relationship between proximal tibiofibular joint cysts and intraneural peroneal nerve ganglia is discussed. Intraosseous cystic lesions, including insertional and degenerative cysts, as well as lesions mimicking cysts of the knee are described and illustrated. Knowledge of the location, characteristic appearance and distinguishing features of cystic masses around the knee as well as potential imaging pitfalls such as normal anatomical recesses and atypical cyst contents on MR imaging aids in allowing a specific diagnosis to be made. This will prevent unnecessary additional investigations and determine whether intra-articular surgery or conservative management is appropriate.


Comparative study of microtubule inhibitors--estramustine and natural podophyllotoxin conjugated PAMAM dendrimer on glioma cell proliferation.
The synthetic estramustine (EM) and natural podophyllotoxin (PODO) anti-mitotic agents that inhibit tubulin polymerization are known anticancer agents. As low bioavailability limits their anticancer properties, we investigated whether conjugation with PAMAM dendrimer (D) could enhance the activity of D-EM and D-PODO by altering their release pattern. Release kinetics indicated synthesized conjugates to be stable against hydrolytic cleavage and showed sustained release characteristics. However, release of D-EM was slow compared to D-PODO conjugate. Antitumor effect of these conjugates on glioma cells revealed (i) increased cell death and cell cycle arrest (ii) decreased migration and (iii) increased tubulin depolymerization as compared to free drug. Importantly, the effects of natural PODO conjugate on glioma cell survival and migration is more pronounced than D-EM.


Effect of polar and non-polar carotenoids on Xanthophylomyces dendrorhous membranes by EPR.
The red yeast Xanthophyllomyces dendrorhous is one of the microbiological production systems for natural carotenoids. High-performance liquid chromatography (HPLC) and electron paramagnetic resonance spectroscopy (EPR) experiments were performed on X. dendrorhous membranes in order to study the effect of incorporation rates of different type of carotenoids. In the case of fluid-phase membranes, it was found that polar carotenoids, such as astaxanthin and cis-astaxanthin, increased the EPR order parameter and decreased the motional freedom and phase-transition temperature. In contrast the non-polar carotenoids beta-cryptoxanthin and beta-carotene decreased the EPR order parameter and increased motional freedom and phase-transition temperature. A noteworthy coherence was observed between the polarities of the strains and the phase-transition temperatures.


HER2 gene amplification and chromosome 17 copy number do not predict survival of patients with resected pancreatic adenocarcinoma.
HER2 gene amplification is an established predictive and prognostic marker in breast cancer. Since there are conflicting reports as to the significance of HER2 gene amplification in pancreatic cancer, we undertook this study. We studied HER2 gene amplification, HER2 copy numbers, and chromosome 17 copy numbers using fluorescence in situ hybridization in 63 cases of resected pancreatic cancer. Sixteen tumors (25%) had HER2 gene amplification, 7 (11%) had increased HER2 copy numbers, and 11 (17%) had increased chromosome 17 copy numbers. No statistical significance was found between the genetic parameters and tumor characteristics, stage, or survival. To the best of our knowledge, this is the largest case series reporting HER2 gene amplification status and its association with tumor characteristics and survival in pancreatic cancer in the literature. Although a significant percentage (25%) of pancreatic cancers demonstrate amplification of the HER2 gene, we find no association of HER2 gene amplification or chromosome 17 hyperploidy with poorer survival.


Effects of outlet obstruction on glucose metabolism of the rabbit urinary bladder.
Bladder outlet obstruction has been shown to cause detrusor contractile dysfunction. To determine if alterations in bladder metabolism may in part underlie these functional defects, we investigated the effects of mild outlet obstruction on the glucose metabolism of the rabbit urinary bladder. Mild outlet obstruction was created in mature male rabbits by the surgical placement of a silicon sleeve around the bladder neck. Two weeks after surgery, the in vitro ability of the obstructed bladder tissues to metabolize glucose was compared to that of the controls. The results can be summarized as follows: 1) The bladder wet weight increased 2.3-fold following two weeks of obstruction. 2) Obstructed bladder tissues had a reduced glucose consumption as compared to the controls. 3) CO2 generation was significantly reduced by 31% in obstructed bladder tissues whereas lactate formation increased significantly by 22%. 4) Tissue concentrations of ATP, creatine phosphate, and glycogen before incubation showed no significant differences between control and obstructed bladder tissues. In summary, bladder tissues following two weeks obstruction showed a decrease in aerobic metabolism and an increase in anaerobic metabolism. Previous studies have indicated that the ability of the bladder to maintain a contraction and empty may be directly related to aerobic metabolism. Therefore, the decrease in aerobic metabolism (even in the presence of increased anaerobic metabolism) may in part explain the decreased ability of the obstructed bladder to empty.


Sexual function in primiparous women: a prospective study.
The aim of this prospective study was to examine the impact of sociodemographic, pregnancy and obstetric characteristics on sexual function 12 months postpartum in primiparous women. We hypothesized that sexual function would decrease after childbirth. Between 1 October 2014 and 1 October 2017, all nulliparous women in early pregnancy registering for maternity health care in Region Örebro County, Sweden, were invited to participate in this prospective study. A total of 958 women were included. Sexual activity and function were measured at early pregnancy, 8 weeks postpartum and 12 months postpartum using the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). The associations between sociodemographic, pregnancy and obstetric characteristics and sexual activity and function from early pregnancy to 12 months postpartum were examined using linear and logistic models based on generalized estimating equations. We found that the prevalence of sexually active women decreased from 98.0% in early pregnancy to 66.7% at 8 weeks postpartum, but increased to 90.0% at 12 months postpartum. Age ≥ 35 years, second-degree perineal tear and current breastfeeding were statistically significant risk factors for sexual inactivity at 12 months postpartum. Poor self-reported health in early pregnancy was statistically significantly associated with decreased sexual function at 12 months postpartum. A majority of women resumed sexual activity at 8 weeks postpartum and most women at 12 months postpartum; the decrease in sexual function at 12 months postpartum was small and few risk factors were observed.


Acute Exposure to Biogenic Nanosilver Produced from Fusarium oxysporum in a Neotropical Fish.
Biogenic nanosilver (bNAg) has emerged as a potentially less toxic alternative to synthetic nanosilver. However, no studies have evaluated its effects on a fish species from the Neotropical region. Thus, our aim was to evaluate the effects of a bNAg on the Neotropical fish Prochilodus lineatus. For this purpose, after 24 h of exposure to 100 µg L-1 of bNAg, blood samples were collected to evaluate hematological, genotoxic, and plasma parameters. Gills and liver were sampled to evaluate biomarkers of oxidative stress and brain samples were used to assess neurotoxicity. The fish presented hyperglycemia, an increased number of erythrocytes, a reduction in antioxidant enzyme activity in both tissues evaluated, and a decrease in lipid peroxidation in the gills. We concluded that P. lineatus is a sensitive species to this nanoparticle, since it presented alterations in several biomarkers after an acute exposure.


Gatekeeping testing via adaptive alpha allocation.
In a typical clinical trial, there are one or two primary endpoints, and a few secondary endpoints. When at least one primary endpoint achieves statistical significance, there is considerable interest in using results for the secondary endpoints to enhance characterization of the treatment effect. Because multiple endpoints are involved, regulators may require that the familywise type I error rate be controlled at a pre-set level. This requirement can be achieved by using "gatekeeping" methods. However, existing methods suffer from logical oddities such as allowing results for secondary endpoint(s) to impact the likelihood of success for the primary endpoint(s). We propose a novel and easy-to-implement gatekeeping procedure that is devoid of such deficiencies. A real data example and simulation results are used to illustrate efficiency gains of our method relative to existing methods.


The measurement of spleen perfusion in man: a non-invasive method using the ratio between Rubidium-81 and its decay product Krypton-81m.
A non-invasive method has been developed for measuring spleen perfusion in man. This involves recording the gamma-ray energy spectra over the spleen following the localisation of Rubidium-81 within the organ by injecting intravenously labelled heat denatured red cells. The spectra are analysed to provide the ratio of Rubidium-81 to its radioactive decay product Krypton-81 m. This ratio is dependent on the rate of perfusion through the organ. The difficulties encountered in applying this steady state method for monitoring tissue perfusion are illustrated and practical means for their solution presented. The results of applying this method to patients with various splenic disorders are presented and compared with those obtained by other workers using different monitoring techniques.


Studies on the subcellular localization and role of glutathione-insulin transhydrogenase in rat liver.
125I-insulin was shown to be internalized in vivo to a discrete population of low-density membranes (ligandosomes), distinct from the +Golgi, endoplasmic reticulum, plasma membrane, and lysosomes. However, analytical subcellular fractionation shows that glutathione-insulin transhydrogenase is localized to the endoplasmic reticulum. Measurement of the specific enzyme activity of glutathione-insulin transhydrogenase showed no differences between normal, diabetic, and hyperinsulinaemic rats. These results suggest that glutathione-insulin transhydrogenase is not directly involved in the subcellular processing of receptor-bound internalized insulin.


Simultaneous development of vocal and physical object combinations by a Grey parrot (Psittacus erithacus): bottle caps, lids, and labels.
On the basis of primarily behavioral data, researchers (e.g., P. M. Greenfield, 1991) have argued (a) that parallel development of communicative and physical object (manual) combinatorial abilities exists in young children; (b) that these abilities initially have a common neural substrate; (c) that a homologous substrate in great apes allows for similar, if limited, parallel development of these 2 abilities; and (d) that such abilities thus may indicate a shared evolutionary history for both communicative and physical behavior (J. Johnson-Pynn, D. M. Fragaszy, E. M. Hirsh, K. E. Brakke, & P. M. Greenfield, 1999). The authors of the present study found a comparable, if limited, parallel combinatorial development in a Grey parrot (Psittacus erithacus). Given the evolutionary distance between parrots and primates, the authors suggest that the search for and arguments concerning responsible substrates and common behavior should be approached with care and should not be restricted to the primate line.


Ondansetron and pregnancy: possible congenital heart defects.
Two cohort studies, including more than 2500 pregnant women exposed to ondansetron in early pregnancy, have raised concerns over an increased risk of congenital heart defects.


Acupuncture treatment for 34 cases of epiphora with dysfunction of lacrimal duct.
We have treated 34 cases of epiphora due to dysfunction of the lacrimal duct with a warm needle puncturing at the Jingming (UB 1) point. The effect was significantly better than that of the control group treated with lacrimal duct irrigation and norflaxacin eye drops (a total effective rate of 91.07% vs. 54.29%).


Fit of metal ceramic crowns cast in Au-1.6 wt% Ti alloy for different abutment finish line curvature.
The purpose of this study was to evaluate the fit of metal ceramic crowns cast in Au-1.6 wt% Ti alloy and investigate the effect of abutment finish line curvature on the fit of crowns. Three types of finish line curvature abutments were prepared (1, 3 and 5mm-curvature). For each type of abutment, five metal ceramic crowns of the facial veneered type were fabricated, which were cast in Au-1.6 wt% Ti alloy. Used as controls, another fifteen specimens were made from a commercially available gold alloy. The fit was measured in the as-cast and after porcelain application. In the as-cast specimens, the greater the finish line curvature was, the larger the gaps exhibited at the mesial and distal margins of copings, compared with labial and lingual margins. The distal margin of copings for 5mm-curvature abutments showed the largest gap (35 (7) microm). After porcelain application, the greater was the finish line curvature, the larger the labial marginal gap became (mean 44, 34, 25 microm, respectively, for 5, 3, 1mm-curvature). However, there was no significant difference on marginal gaps between specimens of Au-1.6 wt% Ti alloy and control gold alloy. This study indicated that the metal ceramic crowns cast in Au-1.6 wt% Ti alloy had equivalent accuracy to those that cast in control gold alloy, and the abutment finish line curvature had a significant effect on the marginal fit of metal ceramic crowns.


A meta-analysis framework to assess the role of units in describing nanoparticle toxicity.
Despite ample research on nanoparticles, their environmental toxicity is still debatable. The lack of consensus is due in part to the challenge of comparing studies because of variability in parameters like test organism, test medium, and duration of experiment. However, the unit used to compare the toxicology of nanoparticles is one variable that experimentalists can control. Traditionally, mass per volume is the most common unit used to make comparisons, but there is growing evidence that alternative units such as surface area per volume or particles per volume may provide a better and more mechanistic measure of toxicity. Herein, we propose and test a meta-analytic framework to study the effect of units on nanotoxicology using data from the NanoE-Tox database, a freely available database containing 1518 toxicology values from 224 published articles of which 42 records met our basic inclusion criteria. These data were augmented with more recent data published over the past five years as archived by the Web of Science citation index. An additional 27 records from 1676 papers met the inclusion criteria and were also included in the analysis. The meta-analysis framework measures the degree of heterogeneity for each of three units (grams/L, particles/L, surface area/L) grouped by the type of test organism, particle chemistry, and manner in which a nanoparticle's size was measured (e.g., nominal particle size reported by the manufacturer vs. measurement of size for particles suspended in the liquid medium used in a subsequent toxicity experiment). The result of the meta-analysis reveals that surface area per volume reduces the heterogeneity in the Ag crustacean subgroup when nanoparticle size was measured in the test medium, and the ZnO crustacean subgroup when nanoparticle size was measured out the test medium and may therefore be a more appropriate estimate of the toxicity of soluble nanoparticles. No subgroups in our analysis showed a reduction in heterogeneity for particles per volume in either soluble or insoluble nanoparticles. The lack of conclusion on insoluble nanoparticles was not due to a limitation of our meta-analysis but rather highlights a critical deficiency in the primary literature. The majority of published studies fail to report common measures of error that are essential for further analysis (i.e. error of the measured nanoparticle size and/or interoperable error of the measured half-maximal concentration of the toxic endpoint). If future nanotoxicity studies report such error, as they should, then the framework of our meta-analysis could be used more broadly to provide a simple, statistically rigorous way to assess the role of units on the toxicity of nanoparticles.


Compartmental models for apical efflux by P-glycoprotein: part 2--a theoretical study on transporter kinetic parameters.
The impact of efflux transporters in intracellular concentrations of a drug can be predicted with modeling techniques. In Part 1, several compartmental models were developed and evaluated. The goal of Part 2 was to apply these models to the characterization and interpretation of saturation kinetic data. The compartmental models from Part 1 were used to evaluate a previously published dataset from cell lines expressing varying levels of P-glycoprotein. Kinetic parameters for the transporter were estimated and compared across models. Fits and errors for all compartmental models were identical. All compartmental models predicted more consistent parameters than the Michaelis-Menten model. The 5-compartment model with efflux out of the membrane predicted differential impact of P-gp upon apical versus basolateral drug exposure. Finally, the saturable kinetics of active efflux along with a permeability barrier was modeled to delineate a relationship between intracellular concentration with or without active efflux versus donor concentration. This relationship was not a rectangular hyperbola, but instead was shown to be a quadratic function. One approach to estimate an in vivo transporter effect is to first model an intracellular Km value from in vitro data, and use this value along with the appropriate tissue transporter expression levels and relative surface area to calculate the relevant apparent Km (or Ki) values. Together with the results from Part 1, these studies suggest that compartmental models can provide a path forward to better utilize in vitro transporter data for in vivo predictions such as physiologically based pharmacokinetic modeling.


Melatonin decreases calcium levels in retinotectal axons of Xenopus laevis by indirect activation of group III metabotropic glutamate receptors.
Melatonin is a neuromodulator that binds to receptors in the retinotectal laminae of the amphibian optic tectum. The effect of melatonin on calcium dynamics in Xenopus retinotectal axons was investigated by imaging retinotectal axons labeled with the fluorescent indicator Fluo-4. Melatonin exerted an inhibitory influence on depolarization-evoked calcium increases, and the melatonin receptor antagonist 4-P-PDOT blocked this effect. Blockade of group III metabotropic receptors (mGluRs) counteracted the effect of melatonin on retinotectal axons. Application of the group II/group III mGluR antagonist MSPG or the group III-selective antagonist MSOP abolished the effect of melatonin. Conversely, this effect was not significantly affected by the group I mGluR antagonist LY367385 nor by EGLU or LY341495 at concentrations that specifically inhibit group II mGluRs. Furthermore, a higher concentration of LY341495 that affects group III mGluRs inhibited the effect of melatonin. The data therefore support the hypothesis that, in retinotectal axons, melatonin reduces cAMP levels, thereby relieving PKA-induced inhibition of group III mGluRs; the newly activated mGluRs in turn inhibit voltage-sensitive calcium channels, leading to a decrease in Ca2+ concentrations. The role of GABA(C) receptors in retinotectal responses was also evaluated. GABA(C) receptor antagonists did not block the effects of melatonin but instead were additive. Moreover, while other studies have shown that in Xenopus tectal cells, GABA(C) receptors mediate inhibition, in retinotectal axons, the opposite appears to occur since depolarization-evoked calcium rises in retinotectal axons were inhibited by GABA(C) receptor blockade. This result suggests that activation of GABA(C) receptors produces an increase in the synaptic excitability of retinotectal axon terminals.


The genesis of planets.
Barely a decade ago scientists who study how planets form had to base their theory on a single example-our solar system. Now they have dozens of mature systems and dozens more in birth throes. No two are alike. The basic idea behind the leading theory of planetary formation--tiny grains stick together and swoop up gas--conceals many levels of intricacy. A chaotic interplay among competing mechanisms leads to a huge diversity of outcomes.


Oxidation of Sb(III) by Shewanella species with the assistance of extracellular organic matter.
Antimony (Sb) is a toxic substance that poses a serious ecological threat when released into the environment. The species and redox state of Sb determine its environmental toxicity and fate. Understanding the redox transformations and biogeochemical cycling of Sb is crucial for analyzing and predicting its environmental behavior. Dissolved organic matter (DOM) in the environment greatly affects the fate of Sb. Microbially produced DOM is a vital component of environmental DOM; however, its specific role in Sb(III) oxidation has not been experimentally confirmed. In this work, the oxidation capacity of several Shewanella strains and their derived DOM to Sb(III) was confirmed. The oxidation rate of Sb(III) shows a positive correlation with DOM concentration, with higher rates observed under neutral and weak alkaline conditions, regardless of the presence of light. Incubation experiments indicated that extracellular enzymes and common reactive oxygen species were not involved in the oxidation of Sb(III). Characteristics of DOM suggests that microbial humic acid-like and fulvic acid-like substances are the potential contributors to Sb(III) oxidation. These findings not only experimentally validate the role of bacterial-derived DOM in Sb(III) oxidation but also reveal the significance of Shewanella and biogenic DOM in the biogeochemical cycling of Sb.


RNA Preparation and RNA-Seq Bioinformatics for Comparative Transcriptomics.
The principal transcriptome analysis is the determination of differentially expressed genes across experimental conditions. For this, the next-generation sequencing of RNA (RNA-seq) has several advantages over other techniques, such as the capability of detecting all the transcripts in one assay over RT-qPCR, such as its higher accuracy and broader dynamic range over microarrays or the ability to detect novel transcripts, including non-coding RNA molecules, at nucleotide-level resolution over both techniques. Despite these advantages, many microbiology laboratories have not yet applied RNA-seq analyses to their investigations. The high cost of the equipment for next-generation sequencing is no longer an issue since this intermediate part of the analysis can be provided by commercial or central services. Here, we detail a protocol for the first part of the analysis, the RNA extraction and an introductory protocol to the bioinformatics analysis of the sequencing data to generate the differential expression results.


Identification of Bermuda grass (Cynodon dactylon)--pollen allergens by electroblotting.
Bermuda grass-pollen proteins were electrophoretically separated on polyacrylamide gels and transferred to nitrocellulose where IgE-binding components were detected by reaction with individual patient's serum and 125I-labeled antihuman IgE. Seventeen pollen components (in the molecular weight (MW) range of 8000 to 94,000 daltons), separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, bound IgE antibodies from a panel of 44 sera from allergic patients. The spectrum of Bermuda grass-pollen IgE-binding components detected is greater in number and wider in MW range than has previously been described. A component of MW 34,000 daltons (fraction 9) bound IgE from 100% of atopic sera tested. This component also bound the greatest quantity of IgE. Electrophoresis and transfer under nondissociating conditions revealed a component of MW 100,000 daltons that also bound IgE antibodies in all 44 sera tested. This component may be an aggregated form of fraction 9. A comparison of the electroblotting results obtained under dissociating and nondissociating conditions suggests once again that allergenic proteins in crude extracts may aggregate or associate during in vitro studies. Electrophoretic transfer analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis may thus be the method of choice for allergen separation and identification.


Correlation between hyoid bone position and airway dimensions in Chinese adolescents by cone beam computed tomography analysis.
This study aimed to investigate the correlation between upper airway dimensions and hyoid bone position in Chinese adolescents based on cone beam computed tomography (CBCT) images. CBCT images from a total of 254 study subjects were included. The upper airway and hyoid bone parameters were measured by Materialism's interactive medical image control system (MIMICS) v.16.01 (Materialise, Leuven, Belgium). The airway dimensions were evaluated in terms of volume, cross-sectional area (CSA), mean CSA, length, anteroposterior dimension of the cross-section (AP), lateral dimension of the cross-section (LAT), and LAT/AP ratio. The hyoid bone position was evaluated using eight linear parameters and two angular parameters. Facial characteristics were evaluated using three linear parameters and three angular parameters. Most hyoid bone position parameters (especially the distance between the hyoid bone and hard palate) were significantly associated with most airway dimension parameters. Significant correlations were also observed between the different facial characteristic parameters and hyoid bone position parameters. Most airway dimension parameters showed significant correlations with linear facial parameters, but they displayed significant correlations with only a few angular facial parameters. These findings provide an understanding of the static relationship between the hyoid bone position and airway dimensions, which may serve as a reference for surgeons before orthodontic or orthognathic surgery.


Costs and benefits of risk factor reduction for coronary heart disease: insights from screening and treatment of serum cholesterol.
The principles of cost-effectiveness analysis are straightforward and can be applied to set priorities among competing uses for resources. This article examines the relationship between serum cholesterol and coronary heart disease (CHD) risk, drawing on information from a number of large intervention trials. The cost-effectiveness of treatment alternatives for elevated serum cholesterol, hypertension, and symptomatic CHD are compared. Concern is expressed that the guidelines issued by the National Cholesterol Education Program extend beyond the available evidence and do not adequately take into account problems with adherence to diet and drug regimens or the cost of widespread implementation. The cost-effectiveness of drug treatment for both high cholesterol and hypertension depends on the populations at which they are targeted.


In vitro analysis of corneal development with monoclonal antibodies.
Anti-corneal monoclonal antibodies, highly selective for corneal stromal and corneal epithelial components, were used to immunohistochemically evaluate differentiation of intact embryonic chick corneas grown in organ culture in the presence or absence of an associated lens. It was observed that both epithelial and stromal components of 5-day corneas initiated expression of their antigens, irrespective of the presence of a lens. This was unlike previous results obtained when 5-day lens-less corneas were explanted to the chorioallantoic membrane, a condition under which epithelial differentiation ensued but stromal differentiation did not. Possibly, in organ culture, the filter support may replace the lens as a substratum for cell migration of neural crest-derived pericorneal mesenchymal cells into the primary corneal stroma. In 5-day organ cultures with lenses, cellular migration into the primary corneal stroma seems to be largely inhibited (also unlike previous results on the chorioallantoic membrane), but mesenchymal cells which had accumulated at the periphery of the eye did express the differentiation antigen.


A modified horizontal capillary puller for fabrication of patch-clamp pipettes.
A simple low-cost modification to a conventional horizontal two-stage micropipette puller is described. It allows the production of pipettes suitable for patch-clamp studies. It requires that the hard-pull stage of the fabrication process be disabled and two heating cycles, each with a different heating filament temperature, be employed. The modification is described specifically for an Industrial Science Associates, Inc. M-1 micropipette puller. However, in principle it should be applicable to any horizontal two-stage puller using a solenoid to generate the pull force.


[Drug treatment of heart failure in chronic kidney disease].
Patients with chronic kidney disease (CKD) exhibit an increased risk to develop heart failure and the presence of heart failure in CKD patients is associated with a poorer prognosis. The following overview article summarizes the current standard of drug treatment of heart failure and discusses special aspects in the treatment of patients with CKD.


The Role of Health in Education and Human Capital: Why an Integrated Approach to School Health Could Make a Difference in the Futures of Schoolchildren in Low-Income Countries.
Healthy students learn better, yet most current investments in schoolchildren focus on education and learning while largely neglecting the health of the learner. Some school-based interventions, such as school feeding and deworming, are already successfully targeted at this age-group, but the efficiency and cost-effectiveness of such programs could be greatly enhanced by better integrated delivery alongside other priority health interventions. A symposium at the society's 68th annual meeting launched a process to explore how integrated delivery of school-based interventions can address prevalent health conditions in school-age children.


Plethysmographic pulse wave amplitude is an effective indicator for intravascular injection of epinephrine-containing epidural test dose in sevoflurane-anesthetized pediatric patients.
Plethysmographic pulse wave amplitude (PPWA) was effective in detecting intravascular injection of epidural test dose with 100% sensitivity and specificity in adults. We evaluated the efficacy of PPWA in detecting intravascular injection of a simulated epidural test dose during sevoflurane anesthesia in pediatric patients. Eighty infants and children were randomized to receive either 0.5 minimal alveolar concentration (MAC) or 1 MAC sevoflurane and nitrous oxide in oxygen. Patients in each anesthesia group were further randomized to receive either 0.1 mL/kg of 1% lidocaine with 1:200,000 epinephrine (0.5 mug/kg of epinephrine) IV to simulate the intravascular injection of epidural test dose or saline. Heart rate (HR), systolic blood pressure (SBP), and PPWA were monitored for 5 min after injection. A positive test response was defined as HR increase > or =10 bpm, SBP increase > or =15 mm Hg, and PPWA decrease > or =10%. Injecting the test dose resulted in an average maximum PPWA decrease by 69% +/- 18% and 58% +/- 14% at 79 +/- 22 and 80 +/- 19 s in the 0.5 MAC and 1 MAC sevoflurane groups, respectively. The sensitivity, specificity, positive predictive, and negative predictive values for PPWA were 100% in both sevoflurane groups, whereas by using HR and SBP criteria, the sensitivity was 90% and 95% respectively during 0.5 MAC sevoflurane anesthesia and 85% for both during 1 MAC sevoflurane anesthesia. PPWA is effective for detection of an intravascular injection of a simulated epidural epinephrine-containing test dose in pediatric patients.


A class of large polysaccharides contains the antigenic determinants for the cytotoxic antibodies in a conventional syngeneic anti-F9 serum as well as a monoclonal antibody prepared against F9 cells.
The molecular natures of the antigenic targets detected by cytotoxic antibodies in both a monoclonal antibody (ECMA-3) made against F9 cells and a conventional mouse anti-F9 serum were investigated. Both of the antibodies precipitated a class of high molecular weight polysaccharides from Nonidet P40 lysates of F9 cells. These molecules were labeled by radioactive galactose and fucose but only poorly by amino acids; in addition, they were fairly resistant to pronase and the digest still had a molecular weight of 70 K or more. Even after extensive pronase digestion the polysaccharides inhibited the cytotoxic activities of the antibodies, suggesting that the antigenic targets reside on the carbohydrate portion. This class of polysaccharides was shown to be a minor component of the characteristic large polysaccharides of F9 cells.


Dopamine receptor subtypes: in vivo biochemical evidence for functional interaction.
SKF 38393, a selective D-1 dopamine (DA) agonist, enhanced the ability of spiperone, a D-2 antagonist, to increase rat striatal DA metabolite concentrations. Conversely, SKF 38393 reduced the abilities of pergolide and LY 171555, D-2 agonists, to decrease striatal DA metabolite concentrations. These findings are discussed in terms of a possible functional interaction between D-1 and D-2 DA receptors.


Muscle sympathetic nerve activity in frontotemporal lobar degeneration is similar to amyotrophic lateral sclerosis.
To determine whether frontotemporal lobar degeneration (FTLD) is associated with similar cardiovascular autonomic dysfunction to that seen in amyotrophic lateral sclerosis (ALS), we compared cardiovascular parameters between ALS patients and patients with FTLD. In ten patients with FTLD (mean age ± SD: 71.6 ± 4.6 years) and 12 patients with ALS (mean age ± SD: 71.4 ± 4.6 years), MSNA (using microneurography), heart rate (HR), and blood pressure (BP) were recorded simultaneously. MSNA was significantly higher in both groups of patients compared with the controls (p < 0.01), while there were no significant differences in MSNA between the patients with FTLD and those with ALS. During head-up tilt, changes in HR, BP, and the frequency of MSNA bursts were smaller in the patients than in controls (p < 0.05 or p < 0.01). Patients with FTLD and ALS showed similar dysfunction of HR, BP, and sympathetic outflow to muscles.


How do mobility restrictions and social distancing during COVID-19 affect oil price?
This paper provides an analysis of the effect of the COVID-19 outbreak on the crude oil price. Using a newly developed air mobility index and Apple's driving trends index, we assess the effect of human mobility restrictions and social distancing during the COVID-19 pandemic on the crude oil price. We apply a quantile regression model, which evaluates different quantiles of the crude oil price. We also conduct an extreme value modeling, which examines the lower tail of the crude oil price distribution. We find that both the air mobility index and driving trends index significantly influence lower and upper quantiles of the WTI crude oil price. The extreme value models suggest that there is a potential risk of a negative crude oil price for a sudden extreme fall of air mobility.


Sequence breakpoints in the aflatoxin biosynthesis gene cluster and flanking regions in nonaflatoxigenic Aspergillus flavus isolates.
Aspergillus flavus populations are genetically diverse. Isolates that produce either, neither, or both aflatoxins and cyclopiazonic acid (CPA) are present in the field. We investigated defects in the aflatoxin gene cluster in 38 nonaflatoxigenic A. flavus isolates collected from southern United States. PCR assays using aflatoxin-gene-specific primers grouped these isolates into eight (A-H) deletion patterns. Patterns C, E, G, and H, which contain 40 kb deletions, were examined for their sequence breakpoints. Pattern C has one breakpoint in the cypA 3' untranslated region (UTR) and another in the verA coding region. Pattern E has a breakpoint in the amdA coding region and another in the ver1 5'UTR. Pattern G contains a deletion identical to the one found in pattern C and has another deletion that extends from the cypA coding region to one end of the chromosome as suggested by the presence of telomeric sequence repeats, CCCTAATGTTGA. Pattern H has a deletion of the entire aflatoxin gene cluster from the hexA coding region in the sugar utilization gene cluster to the telomeric region. Thus, deletions in the aflatoxin gene cluster among A. flavus isolates are not rare, and the patterns appear to be diverse. Genetic drift may be a driving force that is responsible for the loss of the entire aflatoxin gene cluster in nonaflatoxigenic A. flavus isolates when aflatoxins have lost their adaptive value in nature.


Androgen Signaling Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men.
SARS-CoV-2 infection has led to a global health crisis, and yet our understanding of the disease and potential treatment options remains limited. The infection occurs through binding of the virus with angiotensin converting enzyme 2 (ACE2) on the cell membrane. Here, we established a screening strategy to identify drugs that reduce ACE2 levels in human embryonic stem cell (hESC)-derived cardiac cells and lung organoids. Target analysis of hit compounds revealed androgen signaling as a key modulator of ACE2 levels. Treatment with antiandrogenic drugs reduced ACE2 expression and protected hESC-derived lung organoids against SARS-CoV-2 infection. Finally, clinical data on COVID-19 patients demonstrated that prostate diseases, which are linked to elevated androgen, are significant risk factors and that genetic variants that increase androgen levels are associated with higher disease severity. These findings offer insights on the mechanism of disproportionate disease susceptibility in men and identify antiandrogenic drugs as candidate therapeutics for COVID-19.


Political polarization in US residents' COVID-19 risk perceptions, policy preferences, and protective behaviors.
When the novel coronavirus entered the US, most US states implemented lockdown measures. In April-May 2020, state governments started political discussions about whether it would be worth the risk to reduce protective measures. In a highly politicized environment, risk perceptions and preferences for risk mitigation may vary by political inclinations. In April-May 2020, we surveyed a nationally representative sample of 5517 members of the University of Southern California's Understanding America Study. Of those, 37% identified as Democrats, 32% as Republican, and 31% as Third Party/Independent. Overall, Democrats perceived more risk associated with COVID-19 than Republicans, including for getting infected, being hospitalized and dying if infected, as well as running out of money as a result of the pandemic. Democrats were also more likely than Republicans to express concerns that states would lift economic restrictions too quickly, and to report mask use and social distancing. Generally, participants who identified as Third Party/Independent fell in between. Democrats were more likely to report watching MSNBC or CNN (vs. not), while Republicans were more likely to report watching Fox News (vs. not), and Third Party/Independents tended to watch neither. However, political inclinations predicted reported policy preferences, mask use, and social distancing, in analyses that accounted for differences in use of media sources, risk perceptions, and demographic background. In these analyses, participants' reported media use added to the partisan divide in preferences for the timing of lifting economic restrictions and reported protective behaviors. Implications for risk communication are discussed. The online version of this article (10.1007/s11166-020-09336-3) contains supplementary material, which is available to authorized users.


Mechanism of release of the avian rotavirus tRNATrp primer molecule from viral DNA by ribonuclease H during reverse transcription.
Employing enzymatic reactions containing reverse transcriptase and appropriately defined substrates, we have demonstrated that the tRNATrp primer molecule required for the initiation of DNA synthesis is cleaved from viral DNA by an enzymatic activity associated with the reverse transcriptase molecule. Since the alpha subunit of reverse transcriptase facilitates release of the tRNATrp primer from viral DNA and this activity is inhibited by a known inhibitor of reverse-transcriptase-associated RNAase H, it appears that the RNAase H activity, rather than the DNA endonuclease activity, is involved in this reaction. The cleavage site for RNAase H-mediated removal of the tRNATrp primer from viral DNA is located at or near the tRNATrp-viral DNA junction, and transcription of most, if not all, of the tRNATrp-binding site into (+) polarity DNA occurs before RNAase-H-mediated cleavage takes place. These studies indicate that an additional function can be ascribed to the reverse-transcriptase-associated RNAase H activity, which in this instance acts like an endonuclease, not requiring the unblocked termini of an RNA-DNA hybrid molecule for its activity.


Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring.
Low birth weight (LBW) has been associated with common adult-onset chronic diseases, including obesity, cardiovascular disease, type II diabetes and some cancers. The etiology of LBW is multi-factorial. However, recent evidence suggests exposure to antibiotics may also increase the risk of LBW. The mechanisms underlying this association are unknown, although epigenetic mechanisms are hypothesized. In this study, we evaluated the association between maternal antibiotic use and LBW and examined the potential role of altered DNA methylation that controls growth regulatory imprinted genes in these associations. Between 2009-2011, 397 pregnant women were enrolled and followed until delivery. Prenatal antibiotic use was ascertained through maternal self-report. Imprinted genes methylation levels were measured at differentially methylated regions (DMRs) using bisulfite pyrosequencing. Generalized linear models were used to examine associations among antibiotic use, birth weight and DMR methylation fractions. After adjusting for infant gender, race/ethnicity, maternal body mass index, delivery route, gestational weight gain, gestational age at delivery, folic acid intake, physical activity, maternal smoking and parity, antibiotic use during pregnancy was associated with 138 g lower birth weight compared with non-antibiotic use (β-coefficient=-132.99, s.e.=50.70, P=0.008). These associations were strongest in newborns of women who reported antibiotic use other than penicillins (β-coefficient=-135.57, s.e.=57.38, P=0.02). Methylation at five DMRs, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) and PEG3 (P=0.08), was associated with maternal antibiotic use; among these, only methylation at the PLAGL1 DMR was also associated with birth weight. We report an inverse association between in utero exposure to antibiotics and lower infant birth weight and provide the first empirical evidence supporting imprinted gene plasticity in these associations.


Functional aspects of the regeneration of unmyelinated axons in the rat saphenous nerve.
Electrophysiological experiments have been carried out to investigate aspects of unmyelinated axon regeneration in a transected cutaneous nerve. Some comparisons with regeneration of myelinated axons in the same nerve have also been made. By 3 months after injury approximately 80% of the unmyelinated axons that had survived in the proximal stump had regenerated into the distal stump. About the same proportion of myelinated axons had regrown into the distal stump by this time. With both groups of axons there was no marked increase in the amount of regeneration across the injury site with longer recovery times. Conduction velocities in the regenerated unmyelinated axons tended to be slower across the injury site than proximally; the proximal conduction velocities did not differ from those in control nerves. The unmyelinated axons seemed to take longer to resupply the skin than did the myelinated ones, but in both cases the extent of skin innervation had reached about 60% control values by 6 months after the injury.


Genome-wide identification and expression analyses of phenylalanine ammonia-lyase gene family members from tomato (Solanum lycopersicum) reveal their role in root-knot nematode infection.
Phenylalanine ammonia-lyase (PAL) is a key enzyme and rate-limiting enzyme of phenylpropanoid metabolism, which is a very important pathway in plants, and the secondary products it produces play an important role in plant growth and development, disease resistance, and stress resistance responses. However, PALs still lack systematic characterization in tomato. Based on a bioinformatics methods, PAL family genes were identified and characterized from tomato. qRT-PCR was used to study the expression of PAL genes in cultivated tomato after root-knot nematode infection. In this study, 14 and 11 PAL genes were identified in cultivated and wild tomatoes, and phylogenetic analysis classified them into three subfamilies, with different subfamilies of PAL proteins evolving in different directions in monocotyledonous and dicotyledonous plants. The extensive presence of stress, growth, hormone, and light response elements in the promoter sequences of SlPAL (Solanum lycopersicum) and SpenPAL (Solanum pennellii) genes suggests that this family has a critical role in abiotic stress. Collinearity indicates that members of the tomato and Arabidopsis PAL genes family are from the same ancestor, and the SlPAL10 gene is directly homologous to monocotyledonous rice and maize, suggesting that the SlPAL10 gene was present before monocotyledonous differentiation. Two co-expressed gene modules containing PAL genes were screened by WGCNA, and the core genes in the network were mined and functionally annotated by calculating the connectivity of genes within the modules. In addition, the expression of some genes changed significantly after root-knot nematode infection, with up-regulation of 4 genes and down-regulation of 3 genes. This result provides a data reference for the study of PAL family gene functions in tomato, and also provides a potential application for the subsequent selection of PAL genes in tomato for root-knot nematode resistance.


Mechanism of inhibition of tannic acid and related compounds on the growth of intestinal bacteria.
Tannic acid, propyl gallate and methyl gallate, but not gallic acid, were found to be inhibitory to the growth of intestinal bacteria Bacteroides fragilis ATCC 25285, Clostridium clostridiiforme ATCC 25537, C. perfringens ATCC 13124, C. paraputrificum ATCC 25780, Escherichia coli ATCC 25922, Enterobacter cloacae ATCC 13047, Salmonella typhimurium TA98 and S. typhimurium YG1041 at 100-1000 microg/ml in culture broth. Neither Bifidobacterium infantis ATCC 15697 nor Lactobacillus acidophilus ATCC 4356 was inhibited by any of the above compounds up to 500 microg/ml. Tannic acid has a much greater relative binding efficiency to iron than propyl gallate, methyl gallate or gallic acid. The inhibitory effect of tannic acid to the growth of intestinal bacteria may be due to the strong iron binding capacity of tannic acid; whereas the effect of propyl gallate and methyl gallate probably occurs by a different mechanism. The growth of E. coli was restored by the addition of iron to the medium after the precipitate caused by tannic acid was removed. Neither B. infantis nor L. acidophilus require iron for growth. This probably contributes to their resistance to tannic acid. Because tannins are abundant in the human diet, tannins may affect the growth of some intestinal bacteria and thus may have an impact on human health.


Twenty-four-channel high-impedance glove array for hand and wrist MRI at 3T.
To present a novel 3T 24-channel glove array that enables hand and wrist imaging in varying postures. The glove array consists of an inner glove holding the electronics and an outer glove protecting the components. The inner glove consists of four main structures: palm, fingers, wrist, and a flap that rolls over on top. Each structure was constructed out of three layers: a layer of electrostatic discharge flame-resistant fabric, a layer of scuba neoprene, and a layer of mesh fabric. Lightweight and flexible high impedance coil (HIC) elements were inserted into dedicated tubes sewn into the fabric. Coil elements were deliberately shortened to minimize the matching interface. Siemens Tim 4G technology was used to connect all 24 HIC elements to the scanner with only one plug. The 24-channel glove array allows large motion of both wrist and hand while maintaining the SNR needed for high-resolution imaging. In this work, a purpose-built 3T glove array that embeds 24 HIC elements is demonstrated for both hand and wrist imaging. The 24-channel glove array allows a great range of motion of both the wrist and hand while maintaining a high SNR and providing good theoretical acceleration performance, thus enabling hand and wrist imaging at different postures to extract kinematic information.


Pharmacologic treatment of delusions.
Delusions usually respond to antipsychotic medications. When delusions are present within certain diagnostic categories, however, pharmacotherapy other than or in addition to antipsychotic agents is indicated. Many delusional disorders have been found to respond to pimozide even after failing to respond to other antipsychotic agents. Delusions accompanied by affective symptomatology should be treated with both antipsychotic medications and antidepressants or mood stabilizers. When delusions are the result of a medical condition, treatment of the medical condition may lead to resolution of the delusion.


Collaterals that regressed after angioplasty can be recruited to protect the left ventricle in case of an acute occlusion.
A considerable fraction of collaterals has been shown to regress immediately after percutaneous transluminal coronary angioplasty (PTCA), but the fate of these well-developed collaterals is unknown. The authors aimed to show the protective role of these recruitable collaterals in case of an acute myocardial infarction (MI). They identified 22 patients who underwent PTCA and then were rehospitalized owing to acute myocardial infarction. These patients were compared with a group consisting of 48 patients hospitalized owing to acute MI without a history of previous PTCA. Then, the patients with collaterals were compared with the patients without collaterals to define the factors affecting the collateral formation. All the patients with collaterals before PTCA were shown to have collaterals also after AMI, and collateral grades were greater after MI (1.67 +/-0.98) when compared with those before PTCA (0.73 +/-0.7) (p = 0.001). Coronary collaterals were more commonly seen in patients with a history of previous PTCA (p = 0.005), and the grades of collaterals were also higher in these patients when compared with those without PTCA. Left ventricle score indices were lower and left ventricular ejection fractions (LVEF) were higher in patients with a history of PTCA (p = 0.001). Logistic regression analysis revealed that smoking increased the development of collaterals after AMI 3.8 fold, aspirin use 4.1 fold. On the contrary, diabetes mellitus (DM) decreased this 6.67 fold. As a result, well-developed coronary collaterals are preserved even if they have regressed after restoration of flow, and they may become functional and protect the myocardium against acute ischemia.


Structure of an antitumour drug: 9-hydroxy-2,5,11-trimethyl-6H-pyridol[4,3-b]-carbazolium acetate (9-hydroxy-2-methylellipticinium acetate; Celiptium) dihydrate.
C18H17N2O. C2H3O2. 2H3O, Mr = 336.2, monoclinic, C2/c, alpha = 21.789 (2), b = 12.853 (1), c = 14.004 (2) A, beta = 114.80 (1) degree, V = 3560.2 A3, Z = 8, Dm = 1.24, Dx = 1.255 Mg m3, lambda (Cu K alpha) = 1.54178 A, mu = 0.754 mm-1, F(000) = 1584, T = 298 K, R = 0.052 for 2236 observed reflections. Antitumor drug. The crystal structure involves the packing of resonant rings held together by a network of hydrogen bonds involving hydroxyl groups, acetate ions and water molecules. The main feature is the two stacking patterns found together in the crystal structure; this feature appears to differ from other derivatives.


A comparison of venous blood gas analysis with paired specimens collected in syringes and evacuated blood collection tubes.
Venous blood samples collected in evacuated blood collection tubes are generally not considered suitable for measurement of oxygenation status. However, whether pH, pCO2 and HCO3- results from venous blood samples collected in evacuated tubes are reliable remains unclear. Paired samples were collected from 38 healthy volunteers using two collection methods: (1) collection of blood directly into a blood gas syringe and (2) collection of blood into an evacuated tube with subsequent anaerobic transfer into a blood gas syringe. Samples were analyzed for pH, pCO2, HCO3-, and pO2. Samples collected in evacuated tubes showed significant positive mean biases of 0.03 and 7.5 mmHg for pH and pO2, respectively, and significant negative mean biases of 5.0 mmHg and 1.2 mmol/l for pCO2 and HCO3-, respectively. Collection in evacuated tubes resulted in biases exceeding the total allowable errors in 16%, 40%, 21% of samples for pH, pCO2, HCO3-, respectively, when compared to samples collected in syringes directly. Samples for venous blood gas analysis should be collected directly into blood gas syringes for accurate assessment of ventilation and/or acid-base status. Biases observed for samples collected in evacuated tubes are consistent with air contamination and/or vacuum effects.


Groundwater-surface water interactions in a semi-arid irrigated agricultural valley: A hydrometric and tracer-aided approach.
The purpose of this study was to assess hydrological controls (e.g., rainfall, irrigation practices, river discharge, dam operation, evaporation) on surface (SW)- ground water (GW) interactions in an irrigated valley within semi-arid Patagonia Argentina (-65.49 W, -43.29 S). We combined different sampling designs (watershed/sub-watershed scales, longitudinal and monthly samplings) from 2015 to 2019 to investigate the temporal and spatial variation of hydrometrics, electrical conductivity (EC) and stable isotope composition of surface and ground water. Results showed that plant transpiration in the upper basin, evaporation in the middle basin and the reservoir dynamics modified water salinity and left an imprint in stable isotopes. Water tables in the irrigated valley were high (0.5-2 m level from soil surface) and presented higher salinity than river water. Groundwater salinity, temporal variation of water table levels and stable isotopes suggested that groundwater is subjected to evaporation, is recharged from field seepage and, at a lesser extent, from local rainwater. River salinity increased downstream of the irrigated valley during the whole study period (3 years), showing the effects of agriculture and urbanization. EC also responded to the opening and closing of irrigation channels. EC and daily discharge statistical analysis revealed that groundwater recharge the stream below a threshold discharge of 26 m.s-1; with river salinity increasing linearly as daily discharge decrease. This study illustrates the deep modifications that agricultural systems, mainly surface irrigation, produce on semiarid watersheds. Given that SW and GW components are currently not isolated and flow regulation and irrigation practices are playing a critical role in soil quality and river chemistry at low flow conditions, a conjunctive water management strategy must be implemented in order to prevent further land and water quality degradation.


Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Acute Pancreatitis: A Population-Based Cohort Study.
There are conflicting reports on the effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) on acute pancreatitis incidence. The aim was to determine whether use of ACE inhibitors and ARBs is associated with the incidence of acute pancreatitis, compared with use of dihydropyridine calcium channel blockers (dCCBs). We assembled two population-based, new-user, active comparator cohorts using the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository and Office for National Statistics from 1998 to 2018, with follow-up until 2019. The first cohort included 304,083 ACE inhibitor initiators and 194,431 dCCB initiators. The second cohort included 29,160 ARB initiators and 203,610 dCCB initiators. Cox proportional hazards models were fit to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of acute pancreatitis, comparing ACE inhibitors and ARBs, separately, with dCCBs. Models were weighted using standardized mortality ratio weights generated from calendar time-specific propensity scores. ACE inhibitors were associated with an increased risk of acute pancreatitis, compared with dCCBs (64.3 vs 45.2 per 100,000 person-years, respectively; HR 1.45, 95% CI 1.15-1.83). The number needed to harm after 2 and 5 years of use was 2438 and 1019, respectively. In contrast, ARBs were not associated with an increased risk of acute pancreatitis, compared with dCCBs (40.1 vs 47.6 per 100,000 person-years, respectively; HR 0.88, 95% CI 0.60-1.31). ACE inhibitors were associated with a modest increased risk of acute pancreatitis compared with dCCBs. This association should be balanced with the known clinical benefits of ACE inhibitors in hypertension management. In contrast, no association was observed with ARBs.


Factors that influence the implementation of dietary guidelines regarding food provision in centre based childcare services: A systematic review.
Children attending centre based childcare services consume as much as two thirds of their daily dietary requirements while in care. However, such services often fail to provide foods that are consistent with guideline recommendations. Developing strategies to improve childcare service adherence to menu dietary guidelines requires a comprehensive understanding of factors that may impede or promote implementation. The primary aim of this systematic review is to describe factors (barriers and facilitators) that may influence the implementation of menu dietary guidelines regarding food provision in centre-based childcare services and to map these factors to a theoretical framework. Over 7000 citations were identified from all sources. Duplicate abstracts were removed and selection criteria applied. Twelve studies (1994-2015) were included in the review. Dual data extraction was conducted and the reported factors were synthesised using the theoretical domains framework (TDF). Barriers and facilitators identified in qualitative studies were classified into 8 and 10 of the 14 TDF domains. Barriers and facilitators reported in quantitative studies covered 6 and 3 TDF domains respectively. The most common domain of which both barriers and facilitators to the implementation of menu dietary guidelines were identified was 'environmental context and resources'. This is the first study that comprehensively assesses literature to identify factors that influence the implementation of menu dietary guidelines in childcare services utilising a theoretical framework. Findings provide guidance to support researchers and policy makers design strategies to improve menu dietary guideline implementation and, as such have the potential to improve food provision in care.


Similarities and differences of MR findings between Japanese encephalitis and Wilson's disease.
Although Japanese Encephalitis (JE) and Wilson's disease (WD) are different entities, MR findings in both these conditions are quite similar. The purpose of this retrospective study was to find out the similarities and differences between JE and WD on MR imaging. The study group comprised 25 proven cases of JE and 10 cases of WD. Spin echo (SE) TI- and T2-weighted imaging was performed on a 1.5-T MR system. Fourteen of these 35 cases (10 JE, 4 WD) were also examined using T1-weighted magnetization transfer (MT) SE sequence before and after contrast administration. Although both JE and WD showed similar topographical distribution of lesions, predominant involvement of the basal ganglia and thalami, there were some differences. Brain stem lesion was more frequent for WD than for JE, and posteromedial part of the thalami was spared in WD. The lesion characteristics were also different between both; in WD mixed intensity in the basal ganglia and hyperintense linear rim at the peripheral putamen was observed frequently, whereas hyperintense basal ganglia on T2-weighted images, subacute hemorrhage in the thalami and meningeal enhancement were seen only in the patients with JE. These characteristic lesion criteria may help in differentiation of JE from WD on MR imaging.


Characterization of a Honeycomb-Like Scaffold With Dielectrophoresis-Based Patterning for Tissue Engineering.
Seeding and patterning of cells with an engineered scaffold is a critical process in artificial tissue construction and regeneration. To date, many engineered scaffolds exhibit simple intrinsic designs, which fail to mimic the geometrical complexity of native tissues. In this study, a novel scaffold that can automatically seed cells into multilayer honeycomb patterns for bone tissue engineering application was designed and examined. The scaffold incorporated dielectrophoresis for noncontact manipulation of cells and intrinsic honeycomb architectures were integrated in each scaffold layer. When a voltage was supplied to the stacked scaffold layers, three-dimensional electric fields were generated, thereby manipulating cells to form into honeycomb-like cellular patterns for subsequent culture. The biocompatibility of the scaffold material was confirmed through the cell viability test. Experiments were conducted to evaluate the cell viability during DEP patterning at different voltage amplitudes, frequencies, and manipulating time. Three different mammalian cells were examined and the effects of the cell size and the cell concentration on the resultant cellular patterns were evaluated. Results showed that the proposed scaffold structure was able to construct multilayer honeycomb cellular patterns in a manner similar to the natural tissue. This honeycomb-like scaffold and the dielectrophoresis-based patterning technique examined in this study could provide the field with a promising tool to enhance seeding and patterning of a wide range of cells for the development of high-quality artificial tissues.


How Trypanosoma cruzi feasts upon its mammalian host.
Trypanosoma cruzi has a complex relationship with its mammalian host in which parasite and host metabolic networks are intertwined. A genome-wide functional screen of T. cruzi infection in HeLa cells (Caradonna et al., 2013) divulges host metabolic functions and signaling pathways that impact intracellular parasite replication and reveals potential targets for therapeutic exploitation.


Stereoselectivity of cholinesterase inhibition by galanthamine and tolerance in humans.
The effect of galanthamine (GAL) and its 2 major metabolites on human cholinesterases has been explored. Epigalanthamine, a diastereomer of GAL, was 130-times less potent in vitro in its effect on acetylcholinesterase (AChE) in erythrocytes than the parent compound, and it did not differ significantly from the ketone galanthaminone. In vivo, the maximal 36-55% inhibition of AChE was approached 30 min after oral administration of 10 mg GAL. The duration of the catalytic inhibition corresponded to an elimination half-life of approximately 5-7 h. GAL was well tolerated in 8/8 healthy volunteers, and 3/4 Alzheimer patients tolerated the drug up to a daily dose of 40 mg.


Conserved temperature-dependent expression of RNA-binding proteins in cyanobacteria with different temperature optima.
The expression of the rbp genes, which encode small RNA-binding proteins with a single RNA-recognition motif, is known to increase at low temperature in Anabaena variabilis M3. The 5'-untranslated region (UTR) of the rbpA1 gene is involved in the cold-regulation. We compared the regulation of the rbp genes in three strains of cyanobacteria having different temperature optima, namely, a mesophilic strain Anabaena sp. PCC 7120, a thermophilic strain Thermosynechococcus elongatus BP-1, and a psychrophilic Antarctic strain Oscillatoria sp. SU1. In Anabaena 7120 and T. elongatus, all the rbp gene sequences are known, and the 5'-UTR sequences of some rbp genes have a high similarity to the 5'-UTR of rbpA1. We found that transcripts as well as protein products of these rbp genes accumulated at low temperature. In addition, the expression of rbp genes increased at low temperature in the Oscillatoria sp. SU1. This suggests that a mechanism of cold-regulation of rbp genes is common among various species of cyanobacteria that belong to different taxa and have different temperature optima.


Long-term effects of combination treatment comprising low-intensity extracorporeal shockwave therapy and tadalafil for patients with erectile dysfunction: a retrospective study.
This study retrospectively examined the effects of low-intensity extracorporeal shockwave therapy and tadalafil on erectile dysfunction patients. 116 patients got low-intensity extracorporeal shockwave therapy twice weekly for 3 weeks, 5 mg of tadalafil daily for 3 weeks, and adjuvant therapy for 6 months. Group A (1 year), Group B (2 years), Group C (3 years), and Group D (4+ years) were treated patients' follow-up groups. The patients' International Index of Erectile Function-5 (IIEF-5) scores were gathered at the start of treatment via face-to-face interviews and at the end of follow-ups by telephone conversations. IIEF-5 scores and the minimal clinically significant differences were the main outcomes. Mean follow-up length, age, and IIEF-5 scores of the patients were 2 ± 1.16 years, 47.34 ± 12.65 years, and 12.09 ± 3.66 points, respectively. Compared to baseline, treatment increased the median IIEF-5 scores of patients in groups A, B, C, and D by 7 [3-12], 6 [0-8], 7 [1-9], and 6.5 [2.5-10] points, respectively (p = 0.001). 71%, 63%, 65.8%, and 65% of treated patients in groups A, B, C, and D met the minimal clinically significant differences criteria (n = 77). Mild disease patients were 9.14 times more likely to respond to treatment than severe illness patients (OR, 9.14; 95% CI, 1.28-65.46; P = 0.02). Low-intensity extracorporeal shockwave therapy and 5 mg of tadalafil can treat erectile dysfunction for up to 4 years with sustained outcomes. This treatment is optimal for mild illnesses.


Blood carbonmonoxyhaemoglobin levels are chronically elevated in alcoholics treated for detoxification.
Self-reported daily consumption of cigarettes and ethanol was recorded from a group of 59 ethanol-dependent persons admitted to a detoxification clinic at 2000-2400 h and averaged 40 cigarettes per day and 320 g ethanol per day, respectively. In consequence, concentrations of blood COHb and ethanol were high. Mean values for COHb were 8.5 and 9.9% in men and women, respectively, while the corresponding levels for ethanol were 220 and 280 mg/100 ml. Blood acetate concentrations were also elevated and correlated negatively with mixed venous oxygenhaemoglobin concentrations. The mean carbonmonoxyhaemoglobin concentration at 0700 h was found to be approximately 65% of that on admission. Biochemical and haematological analysis, past medical history and current physical examination revealed a high degree of ethanol and/or cigarette-related pathology. Studies on lipid and lipoprotein metabolism in ethanol-dependent persons should take into account their simultaneous high cigarette abuse.


Study of cardiac arrhythmia using zero-crossing analysis.
It has been known for some time that the variability of the R-R intervals in the electrocardiogram yields valuable information concerning the types of arrhythmia which might be present. In this paper, an investigation is made into the application of zero-crossing analysis to the study of such variability. The number of times the R-R interval crosses its mean value over a specified interval of time is counted, and may be associated with a particular characteristic frequency, related to the dominant frequency components of the power spectrum of R-R intervals. Higher order crossing counts may be computed by taking combinations of sum and difference operations on the original time series. The advantage of using zero-crossing analysis over spectral analysis is the computational simplicity of the former. It is demonstrated, by analysing data taken from the MIT-BIH Arrhythmia database, that zero crossing analysis can sometimes be used t distinguish between different arrhythmias, but forethought concerning the number of sum and difference operations to be taken on the original data set is required when computing the higher order crossing counts.


Scoping review of models and frameworks of patient engagement in health services research.
To count and describe the elements that overlap (ie, present in two or more) and diverge between models and frameworks of patient engagement in health services research. Our specific research question was 'what are the elements that underlie models and frameworks of patient engagement in health services research?' Scoping review. On 6-7 July 2021, we searched six electronic databases (ie, CINAHL, Cochrane Database of Systematic Reviews, Joanna Briggs Institute Evidence Based Practice Database, MEDLINE, PsycINFO and Scopus) and Google Scholar for published literature, and ProQuest Dissertations & Theses, Conference Proceedings Citation Index, Google, and key agencies' websites for unpublished (ie, grey) literature, with no date restrictions. These searches were supplemented by snowball sampling. We included published and unpublished literature that presented (a) models or frameworks (b) of patient engagement (c) in health services research. We excluded articles unavailable as full text or not written in English. Two independent reviewers extracted data from included articles using an a priori developed standardised form. Data were synthesised using both quantitative (ie, counts) and qualitative (ie, mapping) analyses. We identified a total of 8069 articles and ultimately included 14 models and frameworks in the review. These models and frameworks were comprised of 18 overlapping and 57 diverging elements, that were organised into six conceptual categories (ie, principles, foundational components, contexts, actions, levels and outcomes) and spanned intrapersonal, interpersonal, process, environmental, and health systems and outcomes domains. There is little overlap between the elements that comprise existing models and frameworks of patient engagement in health services research. Those seeking to apply these models and frameworks should consider the 'fit' of each element, by conceptual category and domain, within the context of their study.


Adenosine Triphosphate Stress Myocardial Strain in Ischemic Heart Disease: An Animal Study with Histological Validation.
It is still challenging for cardiac magnetic resonance (CMR) to detect ischemic heart disease (IHD) without the use of gadolinium contrast. We aimed to evaluate the potential value of adenosine triphosphate (ATP) stress myocardial strain derived from feature tracking (FT) as a novel method for detecting IHD in a swine model. CMR cines, myocardial perfusion imaging at rest and during ATP stress, and late gadolinium enhancement were obtained in both control and IHD swine. Normal, remote, ischemic, and infarcted myocardium were analyzed. The diagnostic accuracy of myocardial strain for infarction and ischemia was assessed using coronary angiography and pathology as reference. Eleven IHD swine and five healthy control swine were enrolled in this study. Strain parameters, even at rest, were associated with myocardial ischemia and infarction(all p < 0.05). The area under receiver operating characteristic curve (AUC) values of all strain parameters for detecting infarcted myocardium exceeded 0.900 (all p < 0.05). The AUC values for detecting ischemic myocardium were as follows: 0.906 and 0.847 for stress and rest radial strain, 0.763 and 0.716 for stress and rest circumferential strain, 0.758 and 0.663 for stress and rest longitudinal strain (all p < 0.001). Heat maps demonstrated that all strain parameters showed mild to moderate correlations with the stress myocardial blood flow and myocardial perfusion reserve (all p < 0.05). CMR-FT-derived ATP stress myocardial strain shows promise as a noninvasive method for detecting myocardial ischemia and infarction in an IHD swine model, with rest strain parameters offering potential as a needle-free diagnostic option.


[Extramedullary lymphosarcoma, erythroblastopenia and gastric adenocarcinoma. Apropos of a case].
The authors report the case of a patient with lymphosarcoma and erythroblastopenia who died following a surgical operation for gastric carcinoma. The erythroblastopenia, corrected by radiotherapy of the lymphosarcoma, reappeared during the relapse. The link between these two diseases seems undoubted. The later appearance of a gastric carcinoma suggested the predisposing role of the first neoplasm, and/or its treatment, through an immunological disorder.