The association of bladder cancer risk with ethnicity, gender, and smoking.
This study examined patterns of invasive bladder cancer by ethnicity and gender. Odds ratios were computed by comparing 593 patients of known smoking status and diagnosed during the period from 1984 to 1988 with a randomly selected referent group using a logistic regression model that adjusted for differences in age and current occupation. Age-adjusted incidence rates for non-Hispanic whites were approximately twice those of Hispanics and Asian and Pacific Islanders. After adjustment for smoking and occupational exposures, the risks did not differ significantly, indicating that ethnic differences in bladder cancer incidence may be related to smoking and occupational exposures. The odds ratio for males relative to females was 5.95 (95% confidence interval (CI), 4.36 to 8.12), after adjustment for ethnicity, smoking status, occupation, and age, suggesting that gender differences not previously identified may play an important role in the etiology of bladder cancer. Odds ratios associated with amount smoked per day, for current smokers relative to nonsmokers, ranged from 1.04 for those smoking less than 1 pack per day (95% CI, 0.62 to 1.71) to 6.84 for those smoking 2 or more packs per day (95% CI, 4.67 to 10.03).


The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis.
Master transcription factors interact with DNA to establish cell type identity and to regulate gene expression in mammalian cells. The genome-wide map of these transcription factor binding sites has been termed the cistrome. Here we show that the androgen receptor (AR) cistrome undergoes extensive reprogramming during prostate epithelial transformation in man. Using human prostate tissue, we observed a core set of AR binding sites that are consistently reprogrammed in tumors. FOXA1 and HOXB13 colocalized at the reprogrammed AR binding sites in human tumor tissue. Introduction of FOXA1 and HOXB13 into an immortalized prostate cell line reprogrammed the AR cistrome to resemble that of a prostate tumor, functionally linking these specific factors to AR cistrome reprogramming. These findings offer mechanistic insights into a key set of events that drive normal prostate epithelium toward transformation and establish the centrality of epigenetic reprogramming in human prostate tumorigenesis.


Effect of membrane dialysis on characteristics of lyophilised chitosan wafers for potential buccal delivery of proteins.
The effect of membrane dialysis on the characteristics of chitosan based lyophilised wafers was investigated. Gels loaded with BSA, glycerol and d-mannitol were lyophilised with or without membrane dialysis and characterised by X-ray diffraction, attenuated total reflectance Fourier transform infra red spectroscopy, circular dichroism, scanning electron microscopy, hydration capacity, in vitro mucoadhesivity and drug dissolution. The dialysed wafers demonstrated enhanced mucoadhesion and drug release properties while newly formed sodium acetate in the undialysed wafers caused increased crystallinity with poor mucoadhesion and drug release properties. Removal of sodium acetate by membrane dialysis is essential for obtaining optimised wafers for potential application to the buccal mucosa surface.


Effects of a controlled family-based health education/counseling intervention.
To describe the effects of a controlled family-based health education/counseling intervention on health behaviors of children with a familial history of cardiovascular diseases (FH-CVDs). The intervention group (IG, n=432) received 5 counseling sessions. The control groups 1 (CG1, n=200) and 2 (CG2, n=423) received no counseling. Outcome measures comprised changes in diet, exercise, and cigarette smoking. The changes in the use of fats and salt, and in exercise, were more favorable in IG than in CG1 and/or CG2. Health education/counseling produced positive effects on diet and nutrition in particular and in part in exercise.


Draft Genome Sequence of Pyrodictium occultum PL19T, a Marine Hyperthermophilic Species of Archaea That Grows Optimally at 105°C.
We report here the draft genome sequence of Pyrodictium occultum PL19(T), a marine hyperthermophilic archaeon. The genome provides insights into molecular and cellular adaptation mechanisms to life in extreme environments and the evolution of early organisms on Earth.


Selective blockade of T-type Ca2+ channels suppresses human breast cancer cell proliferation.
We have measured the expression of T-type Ca2+ channel mRNA in breast cancer cell lines (MCF-7 (ERalpha+) using Western blot and quantitative real-time PCR (Q-RT-PCR). These results revealed that the MCF-7 cells express both alpha1G and alpha1H isoforms of T-type Ca2+ channels. In order to further clarify the role of T-type Ca2+ channels in proliferation, we tested the effects of a selective T-type Ca2+ channel inhibitor NNC-55-0396 on cellular proliferation. MCF-7 (ERalpha+) cellular proliferation was inhibited by the compound. In contrast, NNC-55-0396 at same concentration had no effect on the proliferation of MCF-10A cells, a non-cancer breast epithelial cell line. We also found that message expression of the T-type Ca2+ channels were only expressed in rapidly growing non-confluent cells but not in the cytostatic confluent cells. Knocking down the expression of T-type Ca2+ channels with siRNA targeting both alpha1G and alpha1H resulted in growth inhibition as much as 45%+/-5.0 in MCF-7 cells as compared to controls. In conclusion, our results suggest that T-type Ca2+ channel antagonism/silencing may reduce cellular proliferation in mitogenic breast cells.


Roles of human UDP-glucuronosyltransferases in clearance and homeostasis of endogenous substrates, and functional implications.
Human UDP-glucuronosyltransferases (UGTs) are major phase II enzymes in the drug metabolism system. Despite major advances in characterization of UGT gene family members, their role in clearance and homeostasis of endogenous substrates is insufficiently understood. Endobiotic substrates including bilirubin, serotonin, eicosanoids, steroid hormones, bile acids, thyroxine and fat-soluble vitamins A and D are discussed. Species- and tissue/cell-dependent regulation of UGT expression by ligand-activated transcription factors is often involved in endobiotic homeostasis. However, roles of particular UGTs are often difficult to delineate since they function together with other enzymes and transporters. Better knowledge of endobiotic UGT substrates and consequences of their conjugation may help to understand evolutionary conserved UGT functions.


SciComm Optimizer for Policy Engagement: a randomized controlled trial of the SCOPE model on state legislators' research use in public discourse.
While prior work has revealed conditions that foster policymakers' use of research evidence, few studies have rigorously investigated the effectiveness of theory-based practices. Specifically, policymakers are most apt to use research evidence when it is timely, relevant, brief, and messaged appropriately, as well as when it facilitates interactive engagement. This study sought to experimentally evaluate an enhanced research dissemination intervention, known as the SciComm Optimizer for Policy Engagement (SCOPE), implemented during the COVID-19 pandemic among US state legislators. State legislators assigned to health committees and their staff were randomized to receive the SCOPE intervention. This involved providing academic researchers with a pathway for translating and disseminating research relevant to current legislative priorities via fact sheets emailed directly to officials. The intervention occurred April 2020-March 2021. Research language was measured in state legislators' social media posts. Legislators randomized to receive the intervention, relative to the control group, produced 24% more social media posts containing research language related to COVID-19. Secondary analyses revealed that these findings were driven by two different types of research language. Intervention officials produced 67% more COVID-related social media posts referencing technical language (e.g., statistical methods), as well as 28% more posts that referenced research-based concepts. However, they produced 31% fewer posts that referenced creating or disseminating new knowledge. This study suggests that strategic, targeted science communication efforts may have the potential to change state legislators' public discourse and use of evidence. Strategic science communication efforts are particularly needed in light of the role government officials have played in communicating about the pandemic to the general public.


Gene duplication in bovine brain myelin proteolipid and homology with related proteins.
Analysis of the amino acid sequence of bovine brain myelin proteolipid reveals not only extensive internal homology, but also homology with portions of the myelin basic protein, the peripheral nerve myelin protein, Po, and with the small proteolipid subunit of mitochondrial ATP synthase. These results suggest that the myelin proteolipid gene has been constructed from a small number of genetic elements, and that these elements are also found in non-myelin proteins. Furthermore, the proteolipid appears to have evolved by acquisition of elements from a 'gene pool' over a period of time, rather than by a simple duplication mechanism.


A chimeric protein comprising the immunogenic domains of Mannheimia haemolytica leukotoxin and outer membrane protein PlpE induces antibodies against leukotoxin and PlpE.
Mannheimia haemolytica is a very important pathogen of pneumonia in ruminants. Bighorn sheep (BHS, Ovis canadensis) are highly susceptible to M. haemolytica-caused pneumonia which has significantly contributed to the drastic decline of bighorn sheep population in North America. Pneumonia outbreaks in wild BHS can cause mortality as high as 90%. Leukotoxin is the critical virulence factor of M. haemolytica. In a 'proof of concept' study, an experimental vaccine containing leukotoxin and surface antigens of M. haemolytica developed by us induced 100% protection of BHS, but required multiple booster injections. Vaccination of wild BHS is difficult. But they can be vaccinated at the time of transplantation into a new habitat. Administration of booster doses, however, is impossible. Therefore, a vaccine that does not require booster doses is necessary to immunize BHS against M. haemolytica pneumonia. Herpesviruses are ideal vectors for development of such a vaccine because of their ability to undergo latency with subsequent reactivation. As the first step towards developing a herpesvirus-vectored vaccine, we constructed a chimeric protein comprising the leukotoxin-neutralizing epitopes and the immuno-dominant epitopes of the outer membrane protein PlpE. The chimeric protein was efficiently expressed in primary BHS lung cells. The immunogenicity of the chimeric protein was evaluated in mice before inoculating BHS. Mice immunized with the chimeric protein developed antibodies against M. haemolytica leukotoxin and PlpE. More importantly, the anti-leukotoxin antibodies effectively neutralized leukotoxin-induced cytotoxicity. Taken together, these results represent the successful completion of the first step towards developing a herpesvirus-vectored vaccine for controlling M. haemolytica pneumonia in BHS, and possibly other ruminants.


Does DPP-IV Inhibition Offer New Avenues for Therapeutic Intervention in Malignant Disease?
Dipeptidyl peptidase IV (DPP-IV, CD26) is frequently dysregulated in cancer and plays an important role in regulating multiple bioactive peptides with the potential to influence cancer progression and the recruitment of immune cells. Therefore, it represents a potential contributing factor to cancer pathogenesis and an attractive therapeutic target. Specific DPP-IV inhibitors (gliptins) are currently used in patients with type 2 diabetes mellitus to promote insulin secretion by prolonging the activity of the incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Nevertheless, the modulation of the bioavailability and function of other DPP-IV substrates, including chemokines, raises the possibility that the use of these orally administered drugs with favorable side-effect profiles might be extended beyond the treatment of hyperglycemia. In this review, we critically examine the possible utilization of DPP-IV inhibition in cancer prevention and various aspects of cancer treatment and discuss the potential perils associated with the inhibition of DPP-IV in cancer. The current literature is summarized regarding the possible chemopreventive and cytotoxic effects of gliptins and their potential utility in modulating the anti-tumor immune response, enhancing hematopoietic stem cell transplantation, preventing acute graft-versus-host disease, and alleviating the side-effects of conventional anti-tumor treatments.


[Topical application of analgesic cream for spinal anaesthesia in elective orthopaedic surgery].
Lidocaine-Prilocaine (Emla®) analgesic cream is commonly used for pain relief during puncture in patients receiving spinal anaesthesia. The protocols for this procedure vary widely. A study was conducted in elective orthopaedic surgery to determine the factors influencing the quality of application and those that improve it.


The effect of intraventricular administration of the 5-HT3 receptor agonist 2-methylserotonin on the release of dopamine in the nucleus accumbens: an in vivo chronocoulometric study.
In the present study we have examined the effects of the serotonin3 (5-HT3) agonist 2-methylserotonin (2-Me-5HT) on the dopamine (DA) release in the nucleus accumbens (NAc) of rats using in vivo chronocoulometric recording. The intraventricular (i.c.v.) administration of 2-Me-5HT dose-dependently increased the DA release in the NAc. This effect was blocked by the selective 5-HT3 antagonist BRL-43694 (granisetron), but not by the 5-HT1/5-HT2 antagonist metergoline. The i.c.v. injection of 8-hydroxydipropylaminotetraline (8-OHDPAT, a selective 5-HT1a agonist) or (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, a 5-HT2/5-HT1c agonist) failed to alter the DA release in the NAc. The increase in the DA release produced by 2-Me-5HT was abolished in animals that had received acute bilateral injections of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our results suggest that the 2-Me-5HT-induced DA release in the NAc is mediated by 5-HT3 receptors. In addition, 2-Me-5HT induced effect is dependent upon the impulse flow of DA cells.


Plasma levels of 7-hydroxymethotrexate after high-dose methotrexate treatment.
Thirteen patients with cancer being treated with high-dose methotrexate (MTX) chemotherapy (350-5,000 mg/6 h IV were entered in this study. Plasma levels of MTX and 7-OHMTX, its main circulating metabolite, were measured by an HPLC technique. 7-OHMTX appears rapidly in the blood, reaching a maximum 6-12 h after the beginning of treatment. The elimination of 7-OHMTX is slower than that of MTX, but the elimination half-lives (24-48 h) are not significantly different: 25.2 h for 7-OHMTX versus 20.3 h for MTX. In all cases, 24 h after starting infusion plasma levels of 7-OHMTX exceeded those of MTX. There was a positive and significant correlation between the dose administered and peak plasma 7-OHMTX. Finally, 7-OHMTX formation was shown to be relatively stable throughout the treatment.


An Arab registry for type 1 diabetes: global benefits for type 1 diabetes patients.
The Arab world encompasses twenty-two Arabic-speaking countries, where the rate of consanguinity can exceed 50%. Type 1 diabetes (T1D), a chronic disorder that requires lifelong treatment, is believed to be largely due to genetic predisposition. The objective of this review is to discuss the benefits of establishing an Arab population-based diabetes registry, which will provide a reference for T1D prevalence and incidence. An online search was carried out through various websites, including PubMed, government, hospitals and health ministries of the 22 Arab countries to understand the reporting activities of diabetes in the Arab world. The prevalence and incidence of T1D is variable among Arabs, with the availability of only a few national/regional diabetes registries to support diabetes research, provide reliable data, and to cope with the widespread threat of this disease. Hence, the need of establishing a population based Arab diabetes registry.


Human rhinovirus-specific CD8 T cell responses target conserved and unusual epitopes.
Human Rhinovirus (HRV) is a major cause of common cold, bronchiolitis, and exacerbations of chronic pulmonary diseases such as asthma. CD8 T cell responses likely play an important role in the control of HRV infection but, surprisingly, HRV-specific CD8 T cell epitopes remain yet to be identified. Here, we approached the discovery and characterization of conserved HRV-specific CD8 T cell epitopes from species A (HRV A) and C (HRV C), the most frequent subtypes in the clinics of various pulmonary diseases. We found IFNγ-ELISPOT positive responses to 23 conserved HRV-specific peptides on peripheral blood mononuclear cells (PBMCs) from 14 HLA I typed subjects. Peptide-specific IFNγ production by CD8 T cells and binding to the relevant HLA I were confirmed for six HRV A-specific and three HRV C-specific CD8 T cell epitopes. In addition, we validated A*02:01-restricted epitopes by DimerX staining and found out that these peptides mediated cytotoxicity. All these A*02:01-restricted epitopes were 9-mers but, interestingly, we also identified and validated an unusually long 16-mer epitope peptide restricted by A*02:01, HRVC1791-1806 (GLEPLDLNTSAGFPYV). HRV-specific CD8 T cell epitopes describe here are expected to elicit CD8 T cell responses in up to 87% of the population and could be key for developing an HRV vaccine.


Identification of two downregulated circRNAs in patients with acute B-lymphocytic leukemia.
Acute B-lymphocytic leukemia (B-ALL) is associated with a high mortality rate, with no effective treatment strategies available. The identification of diagnostic and prognostic biomarkers of B-ALL can contribute to the development of novel therapeutic methods and drugs, which can improve the survival outcomes of patients with B-ALL. The present study aimed to identify downregulated circular RNAs (circRNAs) in patients with B-ALL. RNA sequencing was performed to construct the circRNA expression profiles in B-ALL cells and normal human lymphoblasts. The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. In addition, reverse transcription-quantitative (RT-q)PCR analysis was performed to detect the expression levels of the downregulated circRNAs. A total of 263 differentially expressed circRNAs were identified, including 76 upregulated and 187 downregulated circRNAs, respectively. The upregulated circRNAs were mainly enriched in 'macromolecule modification', 'protein modification' and 'cellular protein modification processes', while the downregulated circRNAs were mainly enriched in the 'negative regulation of RNA biosynthetic processes', 'natural killer cell-mediated cytotoxicity' and 'viral carcinogenesis'. RT-qPCR analysis demonstrated that two of the downregulated circRNAs (hsa_circ_0000745 and chr15:87949594-87966067-), identified during microarray analysis were also significantly downregulated in Ball-1 cells and B-ALL bone marrow samples. Thus, these circRNAs may serve as biomarkers for patients with B-ALL.


A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth.
A substantial fraction of eukaryotic transcripts are considered long non-coding RNAs (lncRNAs), which regulate various hallmarks of cancer. Here, we discovered that the lncRNA HOXB-AS3 encodes a conserved 53-aa peptide. The HOXB-AS3 peptide, not lncRNA, suppresses colon cancer (CRC) growth. Mechanistically, the HOXB-AS3 peptide competitively binds to the ariginine residues in RGG motif of hnRNP A1 and antagonizes the hnRNP A1-mediated regulation of pyruvate kinase M (PKM) splicing by blocking the binding of the ariginine residues in RGG motif of hnRNP A1 to the sequences flanking PKM exon 9, ensuring the formation of lower PKM2 and suppressing glucose metabolism reprogramming. CRC patients with low levels of HOXB-AS3 peptide have poorer prognoses. Our study indicates that the loss of HOXB-AS3 peptide is a critical oncogenic event in CRC metabolic reprogramming. Our findings uncover a complex regulatory mechanism of cancer metabolism reprogramming orchestrated by a peptide encoded by an lncRNA.


Ruptured intracranial aneurysms. The influence of sex and fibromuscular dysplasia upon prognosis.
From a statistical analysis of a series of 214 cases of ruptured intracranial aneurysms, it was demonstrated that only four parameters among those collected on the admission day, are predictive of the final functional result: sex (p less than 0.001); age (p less than 0.02); clinical grade (p less than 0.001) and angiographic spasm (p less than 0.01). The surprisingly poor prognosis in women was explained by the higher frequency of spasm (p less than 0.005). Aneurysms in women predominated on the intracranial carotid artery (38%) and were frequently multiple (12%). A further angiographic study on 87 cases was then carried out including a systematic investigation of the cervical part of the vessels; it permitted one to identify angiographic features of fibromuscular dysplasia (FMD) on the cervical vessels in 20 cases. In those cases it was also observed that there was a marked female predominance (F/M = 5.6), a frequent localization on the internal carotid artery (50%), a high rate of multiple aneurysms (60%) and a poor prognosis related to spasm (50%). Therefore, intracranial aneurysms appear far more frequently than usually reported, to be related to FMD. The worse prognosis of ruptured intracranial aneurysms in females can be, at least partly explained by the association with FMD and the frequent occurrence of spasm. A careful investigation of patients exhibiting features of FMD in order to detect intracranial aneurysms before rupture, is suggested.


Evaluating sucking maturation using two pressure thresholds.
The Medoff-Cooper Nutritive Sucking Apparatus (M-CNSA) has been used to objectively measure sucking maturation in preterm infants. The M-CNSA is able to accurately detect sucking pressures less than 20mmHg, however lower pressure thresholds have not previously been used in research. To determine if differences are observed in the number of sucks and maturation in the number of sucks over time when the minimum pressure threshold used to detect a suck is 7mmHg compared to 20mmHg using the M-CNSA. Descriptive. A convenience sample of 171 healthy premature infants born between 29 and 34weeks gestational period who were part of a larger randomized controlled study. The number of sucks detected during weekly five-minute oral feeding observations using 7mmHg and 20mmHg. Significantly more sucks were detected using the 7mmHg vs 20mmHg threshold at all time points. At both pressure thresholds, the mean number of sucks detected during the five minute feeding observation increased over time. The difference in the number of sucks detected at 7 and 20mmHg did not change over time (p=0.50). Using the lower threshold of 7mmHg compared to 20mmHg resulted in more sucks detected while consistently measuring improvement in sucking over time. Detection of more sucks and sucks at a lower pressure threshold allows clinicians and researchers to more accurately assess oral feeding skills among premature infants.


Operative modification for the prevention of device-related infection during NIPRO extracorporeal left ventricular assist device implantation.
An operative modification in which the NIPRO left ventricular assist device (LVAD) cannulas are passed through the intraperitoneal cavity is performed as the first-choice standard technique in our institution. Eighteen consecutive patients who underwent NIPRO LVAD implantation as heart transplantation candidates were enrolled in this study. The cannulas were passed through the intraperitoneal cavity in 11 patients (Group IP) and the extraperitoneal space in 7 patients (Group EP). A device-related major infection was defined as bloodstream infection and/or abscess formation in the deep tissue space. Device-related major infection occurred in 6 patients in Group IP and in 6 patients in Group EP. Of these patients, 3 patients in Group IP and 5 patients in Group EP suffered from uncontrollable bloodstream infection and finally died of development into multiple organ failure and/or cerebrovascular accidents. The actuarial rates of freedom from device-related major infection at 6 months after LVAD implantation were 100 % in Group IP and 38 % in Group EP, respectively (p = 0.02). Moreover, the actuarial survival rates after the initial device-related major infection in Group IP could be significantly higher than in Group EP (83 and 67 % at 6 months, p = 0.03). We demonstrated that this operative modification can contribute to prevention of progression of superficial skin infection to critical infection and to extension of the survival duration after the initial device-related major infection.


Facial trauma among victims of terrestrial transport accidents.
In developing countries, terrestrial transport accidents - TTA, especially those involving automobiles and motorcycles - are a major cause of facial trauma, surpassing urban violence. This cross-sectional census study attempted to determine facial trauma occurrence with terrestrial transport accidents etiology, involving cars, motorcycles, or accidents with pedestrians in the northeastern region of Brazil, and examine victims' socio-demographic characteristics. Morbidity data from forensic service reports of victims who sought care from January to December 2012 were analyzed. Altogether, 2379 reports were evaluated, of which 673 were related to terrestrial transport accidents and 103 involved facial trauma. Three previously trained and calibrated researchers collected data using a specific form. Facial trauma occurrence rate was 15.3% (n=103). The most affected age group was 20-29 years (48.3%), and more men than women were affected (2.81:1). Motorcycles were involved in the majority of accidents resulting in facial trauma (66.3%). The occurrence of facial trauma in terrestrial transport accident victims tends to affect a greater proportion of young and male subjects, and the most prevalent accidents involve motorcycles.


Serial cardioversion by class IC Drugs during 4 months of persistent atrial fibrillation in the goat.
The success rate of pharmacological cardioversion of atrial fibrillation (AF) in patients depends on the duration of AF. It is unknown to what extent AF-induced structural atrial remodeling contributes to this loss of efficacy. In 10 goats, persistent AF was induced by repetitive burst pacing. During a time period of 16 weeks, the efficacy of flecainide and cibenzoline to cardiovert AF was investigated by serial cardioversion. The drugs were administered intravenously at a rate of 0.1 mg/kg/min. AF cycle length (AFCL) was continuously monitored. Drug infusion was continued until AF was successfully cardioverted or the QRS duration was prolonged about twofold. The average atrial cycle length during persistent AF was 104 +/- 10 msec and did not change during the 16-week period. The success rate of cardioversion by flecainide and cibenzoline decreased with the duration of AF from 60% to 17% and from 80% to 63%. In goats that failed to cardiovert, sinus rhythm was not restored despite a twofold prolongation of the AF cycle length (respectively from 96 +/- 5 msec to 168 +/- 30 msec (flecainide) and 203 +/- 26 msec (cibenzoline)). The sensitivity of AF for Class IC drugs was not altered with time, and the dose-dependent effect on AFCL remained the same (flecainide: 8 +/- 5 vs 7 +/- 2 msec/mg/kg (P = 0.70) and cibenzoline: 13 +/- 3 vs 13 +/- 5 msec/mg/kg (P = 0.95)). In animals in which cardioversion remained possible, the critical AFCL at which cardioversion occurred increased from 96 +/- 5 msec to 211 msec (flecainide) and 189 +/- 24 msec (cibenzoline). The progressive loss of efficacy of Class IC drugs to cardiovert AF of longer duration is not due to a decrease in the sensitivity of remodeled atrial myocardium for Class IC drugs. Failure of cardioversion was due to an increase in the critical AF cycle length required for pharmacological cardioversion.


Meperidine does not block the cholinergic effects of oxotremorine.
Meperidine (20 and 40 mg/kg, IP) did not block the cholinergic effects (tremor, salivation, and tearing) produced by oxotremorine (0.4 mg/kg, SC) in rats, whereas atropine blocked these three effects (10 mg/kg, 2.5 mg/kg and 0.08 mg/kg, respectively.


Contrast agent increases Doppler velocities and improves reproducibility of aortic valve area measurements in patients with aortic stenosis.
Observer variability may limit assessment of aortic stenosis by Doppler echocardiography. This study aimed to assess whether echocardiographic contrast agent improves reproducibility of aortic valve area (AVA) measurements for patients with aortic stenosis. In all, 20 patients with aortic stenosis (67 +/- 10 years old) underwent noncontrast and contrast Doppler echocardiography on 2 occasions, 3 weeks apart. Intraobserver and interobserver coefficients of reproducibility were 0.36 and 0.20 cm for left ventricular outflow tract (LVOT) diameter, and 0.38 and 0.24 cm(2) for AVA, respectively. Although intraobserver reproducibility was unaffected, contrast improved interobserver reproducibility for LVOT diameter (mean of differences -0.02 +/- 0.07 cm vs 0.01 +/- 0.10 cm, P <.05) and AVA (mean of differences 0.02 +/- 0.10 cm(2) vs 0.07 +/- 0.12 cm(2), P <.05). Prevalve and postvalve velocities were increased with contrast compared with noncontrast imaging (prevalve, 1.07 +/- 0.20 vs 0.94 +/- 0.19 m/s, P <.01; postvalve, 3.76 +/- 0.87 vs 3.47 +/- 0.78 m/s, P <.01). We conclude that contrast significantly increases Doppler velocities and produces modest improvements in reproducibility of LVOT diameter and AVA. We suggest that, when assessing patients with aortic stenosis, contrast agents should be considered in patients who are difficult to image with poor baseline LVOT images or Doppler studies, or where there is poor interobserver reproducibility.


Weakly hydrated anions bind to polymers but not monomers in aqueous solutions.
Weakly hydrated anions help to solubilize hydrophobic macromolecules in aqueous solutions, but small molecules comprising the same chemical constituents precipitate out when exposed to these ions. Here, this apparent contradiction is resolved by systematically investigating the interactions of NaSCN with polyethylene oxide oligomers and polymers of varying molecular weight. A combination of spectroscopic and computational results reveals that SCN- accumulates near the surface of polymers, but is excluded from monomers. This occurs because SCN- preferentially binds to the centre of macromolecular chains, where the local water hydrogen-bonding network is disrupted. These findings suggest a link between ion-specific effects and theories addressing how hydrophobic hydration is modulated by the size and shape of a hydrophobic entity.


Mesenchymal deficiency of Notch1 attenuates bleomycin-induced pulmonary fibrosis.
Notch signaling pathway is involved in the regulation of cell fate, differentiation, proliferation, and apoptosis in development and disease. Previous studies suggest the importance of Notch1 in myofibroblast differentiation in lung alveogenesis and fibrosis. However, direct in vivo evidence of Notch1-mediated myofibroblast differentiation is lacking. In this study, we examined the effects of conditional mesenchymal-specific deletion of Notch1 on pulmonary fibrosis. Crossing of mice bearing the floxed Notch1 gene with α2(I) collagen enhancer-Cre-ER(T)-bearing mice successfully generated progeny with a conditional knockout (CKO) of Notch1 in collagen I-expressing (mesenchymal) cells on treatment with tamoxifen (Notch1 CKO). Because Notch signaling is known to be activated in the bleomycin model of pulmonary fibrosis, control and Notch1 CKO mice were analyzed for their responses to bleomycin treatment. The results showed significant attenuation of pulmonary fibrosis in CKO relative to control mice, as examined by collagen deposition, myofibroblast differentiation, and histopathology. However, there were no significant differences in inflammatory or immune cell influx between bleomycin-treated CKO and control mouse lungs. Analysis of isolated lung fibroblasts confirmed absence of Notch1 expression in cells from CKO mice, which contained fewer myofibroblasts and significantly diminished collagen I expression relative to those from control mice. These findings revealed an essential role for Notch1-mediated myofibroblast differentiation in the pathogenesis of pulmonary fibrosis.


Systems biological assessment of altered cytokine responses to bacteria and fungi reveals impaired immune functionality in schizophrenia.
Evidence suggests that complex interactions between the immune system and brain have important etiological and therapeutic implications in schizophrenia. However, the detailed cellular and molecular basis of immune dysfunction in schizophrenia remains poorly characterized. To better understand the immune changes and molecular pathways, we systemically compared the cytokine responses of peripheral blood mononuclear cells (PBMCs) derived from patients with schizophrenia and controls against bacterial, fungal, and purified microbial ligands, and identified aberrant cytokine response patterns to various pathogens, as well as reduced cytokine production after stimulation with muramyl dipeptide (MDP) in schizophrenia. Subsequently, we performed single-cell RNA sequencing on unstimulated and stimulated PBMCs from patients and controls and revealed widespread suppression of antiviral and inflammatory programs as well as impaired chemokine/cytokine-receptor interaction networks in various immune cell subpopulations of schizophrenic patients after MDP stimulation. Moreover, serum MDP levels were elevated in these patients and correlated with the course of the disease, suggesting increased bacterial translocation along with disease progression. In vitro assays revealed that MDP pretreatment altered the functional response of normal PBMCs to its re-stimulation, which partially recapitulated the impaired immune function in schizophrenia. In conclusion, we delineated the molecular and cellular landscape of impaired immune function in schizophrenia, and proposed a mutual interplay between innate immune impairment, reduced pathogen clearance, increased MDP translocation along schizophrenia development, and blunted innate immune response. These findings provide new insights into the pathogenic mechanisms that drive systemic immune activation, neuroinflammation, and brain abnormalities in schizophrenia.


Previous and active tuberculosis increases risk of death and prolongs recovery in patients with COVID-19.
There is a growing literature on the association of SARS-CoV-2 and other chronic conditions, such as noncommunicable diseases. However, little is known about the impact of coinfection with tuberculosis. We aimed to compare the risk of death and recovery, as well as time-to-death and time-to-recovery, in COVID-19 patients with and without tuberculosis. We created a 4:1 propensity score matched sample of COVID-19 patients without and with tuberculosis, using COVID-19 surveillance data in the Philippines. We conducted a longitudinal cohort analysis of matched COVID-19 patients as of May 17, 2020, following them until June 15, 2020. The primary analysis estimated the risk ratios of death and recovery in patients with and without tuberculosis. Kaplan-Meier curves described time-to-death and time-to-recovery stratified by tuberculosis status, and differences in survival were assessed using the Wilcoxon test. The risk of death in COVID-19 patients with tuberculosis was 2.17 times higher than in those without (95% CI: 1.40-3.37). The risk of recovery in COVID-19 patients with tuberculosis was 25% lower than in those without (RR = 0.75,05% CI 0.63-0.91). Similarly, time-to-death was significantly shorter (p = .0031) and time-to-recovery significantly longer in patients with tuberculosis (p = .0046). Our findings show that coinfection with tuberculosis increased morbidity and mortality in COVID-19 patients. Our findings highlight the need to prioritize routine and testing services for tuberculosis, although health systems are disrupted by the heavy burden of the SARS-CoV-2 pandemic.


A body shape index (ABSI) is associated inversely with post-menopausal progesterone-receptor-negative breast cancer risk in a large European cohort.
Associations of body shape with breast cancer risk, independent of body size, are unclear because waist and hip circumferences are correlated strongly positively with body mass index (BMI). We evaluated body shape with the allometric "a body shape index" (ABSI) and hip index (HI), which compare waist and hip circumferences, correspondingly, among individuals with the same weight and height. We examined associations of ABSI, HI, and BMI (per one standard deviation increment) with breast cancer overall, and according to menopausal status at baseline, age at diagnosis, and oestrogen and progesterone receptor status (ER+/-PR+/-) in multivariable Cox proportional hazards models using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. During a mean follow-up of 14.0 years, 9011 incident breast cancers were diagnosed among 218,276 women. Although there was little evidence for association of ABSI with breast cancer overall (hazard ratio HR = 0.984; 95% confidence interval: 0.961-1.007), we found borderline inverse associations for post-menopausal women (HR = 0.971; 0.942-1.000; n = 5268 cases) and breast cancers diagnosed at age ≥ 55 years (HR = 0.976; 0.951-1.002; n = 7043) and clear inverse associations for ER + PR- subtypes (HR = 0.894; 0.822-0.971; n = 726) and ER-PR- subtypes (HR = 0.906; 0.835-0.983 n = 759). There were no material associations with HI. BMI was associated strongly positively with breast cancer overall (HR = 1.074; 1.049-1.098), for post-menopausal women (HR = 1.117; 1.085-1.150), for cancers diagnosed at age ≥ 55 years (HR = 1.104; 1.076-1.132), and for ER + PR + subtypes (HR = 1.122; 1.080-1.165; n = 3101), but not for PR- subtypes. In the EPIC cohort, abdominal obesity evaluated with ABSI was not associated with breast cancer risk overall but was associated inversely with the risk of post-menopausal PR- breast cancer. Our findings require validation in other cohorts and with a larger number of PR- breast cancer cases.


The use of fluoroquinolones in chronic otitis suppurativa.
The present review covers fluoroquinolone usage in chronic otitis suppurativa (COS) in case of chronic otitis media, cholesteatoma, radical mastoid cavity infection and chronic or relapsing otitis externa. A total of six publications were included in the final evaluation. Enoxacin was effective in 35%; ciprofloxacin (five publications) was used in 82 patients with 67% effectivity in otitis externa and otitis media and 61% effectivity in radical mastoid cavity infection. No serious adverse reactions were reported. The promising efficacy of otitis media and otitis externa and safety profile needs further confirmation in double blind prospective clinical studies, that will provide a firm basis for changing the current treatment schedules of COS.


A computerised program for TPN.
A computerised program devised to manage patients undergoing TPN has been operating in the Parenteral and Enteral Nutrition Unit of the II Clinica Chirurgica of the University of Rome. The program includes sections to manage information, monitoring and therapy. The package was compiled using the new Language C, which is well adapted to our model. In a pilot study the program was successfully applied to the management of 15 patients. Computers and information technology have developed to the point where they are well suited to this type of biological application. Language C, which in this study, was used for the first time in this field, offers practically unlimited possibilities for development.


Determination of basic pharmaceuticals in human serum by hydrophilic interaction capillary electrochromatography.
Hydrophilic interaction capillary electrochromatography (HI-CEC) for the determination of basic pharmaceuticals spiked in human serum is described. The organic modifier content, ionic strength, and pH value of the mobile phase as well as the applied voltage are optimized for separation and elution of these drug analytes. Excellent separation was achieved for drugs using a mobile phase composition of 80% v/v acetonitrile in 100 mM triethylamine phosphate (TEAP) buffer at pH 2.8 with column efficiencies for analytes more than 200,000 plates/m. The samples of human serum spiked with basic drugs were directly injected after a simple acetonitrile treatment. The linear range and reproducibility of these basic drugs using an external and internal standard method were compared. As a result, the reproducibility could be greatly improved by using the internal standard method. Good calibration curves with regression coefficients more than 0.998 in the range of 5-160 microg/mL were observed with the internal standard method. The limits of quantitation, based on standards with acceptable relative standard deviations (RSDs), were below 5 microg/mL. The intra- and inter-day precisions, determined as RSDs, were less than 4.57%.


BMP and Hedgehog signaling during the development of scleral ossicles.
Bone development is a complex process, involving multiple tissues and hierarchical inductive interactions. The study of skeletal development has largely focused on endochondral bones while intramembranous bones, such as the scleral ossicles within the avian eye, have received less attention. Our previous research directly demonstrated the involvement of sonic hedgehog and suggested the involvement of bmp2 and 4 during the development of scleral ossicles. The bones of the sclerotic ring are induced by overlying conjunctival papillae at HH 35 and 36. Here, we examine the spatial and temporal expression patterns of ptc1, ihh, bmp2, bmp4 and bmp7. We show that the cells of conjunctival papillae express ptc1, ihh and bmp2 at these stages; coincident with shh expression previously described. Interestingly, both ihh and ptc1 are also expressed in the mesenchyme underlying the papillae unlike shh and bmp2. Bmp4 and bmp7 are not expressed in these regions at any stages examined. Furthermore, using Noggin soaked beads implanted adjacent to papillae, we provide direct evidence that the BMP family of genes are important factors in the development of scleral ossicles. Localized inhibition of BMPs in this way causes a reduced expression of ihh in the surrounding tissue demonstrating that the BMP and Hedgehog pathways interact. Our data also demonstrates that the sclerotic ring has an intrinsic ability to compensate for missing elements. The scleral ossicle system provides a unique opportunity to investigate the epithelial-mesenchymal induction of intramembranous bones of the vertebrate skull.


The Binding Mode Prediction and Similar Ligand Potency in the Active Site of Vitamin D Receptor with QM/MM Interaction, MESP, and MD Simulation.
Non-secosteroidal ligands are well-known vitamin D receptor (VDR) agonists. In this study, we described a combined QM/MM to define the protein-ligand interaction energy a strong positive correlation in both QM-MM interaction energy and binding free energy against the biological activity. The molecular dynamics simulation study was performed, and specific interactions were extensively studied. The molecular docking results and surface analysis shed light on steric and electrostatic complementarities of these non-secosteroidal ligands to VDR. Finally, the drug likeness properties were also calculated and found within the acceptable range. The results show that bulky group substitutions in side chain decrease the VDR activity, whereas a small substitution increased it. Functional analyses of H393A and H301A mutations substantiate their roles in the VDR agonistic and antagonistic activities. Apart from the His393 and His301, two other amino acids in the hinge region viz. Ser233 and Arg270 acted as an electron donor/acceptor specific to the agonist in the distinct ligand potency. The results from this study disclose the binding mechanism of VDR agonists and structural modifications required to improve the selectivity.


Studies on Tyzzer's disease: isolation and propagation of Bacillus piliformia.
Mice from a colony with subclinical Tyzzer's disease were treated with prednisolone in order to activate a Bacillus piliformis infection. From the livers of these mice the organism was isolated and serially passaged in embryonated eggs. It resisted heating at 75 degrees C for 20 minutes and was still infective after storage at -80 degree C for 24 days, but not for 52 days or more. Infectively was maintained for more than a year by storing infectious liver tissue at -190 degrees C. B. piliformis was also isolated from the liver of a mouse with naturally-occurring Tyzzer's disease and maintained for more than 300 passages. Mice inoculated with different egg passages developed fatal Tyzzer's disease and B. piliformis was reisolated from their livers.


Interaction between phorbol esters and phospholipid in a monolayer model membrane.
The possible molecular interaction between phorbol esters and a phospholipid was examined in monolayer films at an air-water interface. The surface pressure isotherms indicated that, at close-to-physiological pressure, there existed a repulsive interaction between the phospholipid and biologically active phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and phorbol 12,13-didecanoate (PDD). There was a close parallelism between the relative biological potency of different phorbol esters, as tumour promoters, and the magnitude of their repulsive interaction with the phospholipid. These findings raise the possibility that a biophysical interference of phorbol esters with the phospholipid domain of biological membranes may represent an important determinant of their biological actions.


Determining the best method for first-line assessment of neonatal blood glucose levels.
To evaluate and compare the accuracy and performance of two electrochemical glucose meters. To determine the user acceptability of these glucose meters and the ABL 620 Blood Gas Analyser (Radiometer, Copenhagen, Denmark) with an electrochemical glucose oxidase electrode for use in a Level 2 special care baby unit. A total of 108 blood samples were collected from 47 babies at risk for hypoglycaemia. The blood glucose level was measured with two glucose meters, the Advantage Glucose Meter (Roche Diagnostics, Castle Hill, Australia) and the Precision-G Blood Glucose Testing System (Medisense, Melbourne, Australia), and the true blood glucose (TBG) measured with the ABL 620 blood gas analyser. Results from the glucose meters were compared with the TBG (as a percentage of the TBG). The mean (SD) percentage difference between the Advantage Glucose Meter and TBG was 4.5% (12. 5), and Precision-G Glucose Meter and TBG was 15.4% (12.4). The sample haematocrit did not significantly influence the glucose meter/TBG differences. There was an overall preference by the nursing staff for the Advantage Glucose Meter. The Advantage Glucose Meter was significantly more accurate than the Precision-G with similar precision. It was the preferred method of screening for neonatal hypoglycaemia.


An mTORC1-to-CDK1 Switch Maintains Autophagy Suppression during Mitosis.
Since nuclear envelope breakdown occurs during mitosis in metazoan cells, it has been proposed that macroautophagy must be inhibited to maintain genome integrity. However, repression of macroautophagy during mitosis remains controversial and mechanistic detail limited to the suggestion that CDK1 phosphorylates VPS34. Here, we show that initiation of macroautophagy, measured by the translocation of the ULK complex to autophagic puncta, is repressed during mitosis, even when mTORC1 is inhibited. Indeed, mTORC1 is inactive during mitosis, reflecting its failure to localize to lysosomes due to CDK1-dependent RAPTOR phosphorylation. While mTORC1 normally represses autophagy via phosphorylation of ULK1, ATG13, ATG14, and TFEB, we show that the mitotic phosphorylation of these autophagy regulators, including at known repressive sites, is dependent on CDK1 but independent of mTOR. Thus, CDK1 substitutes for inhibited mTORC1 as the master regulator of macroautophagy during mitosis, uncoupling autophagy regulation from nutrient status to ensure repression of macroautophagy during mitosis.


Right atrial indexed volume in healthy adult population: reference values for two-dimensional and three-dimensional echocardiographic measurements.
Current guidelines do not recommend routine assessment of right atrial volume due to the lack of standardized data. Three-dimensional wall-motion tracking (3D-WMT) is a new technology that allows us to calculate volumes without any geometric assumptions. The aim of this study was to define the indexed reference values for two-dimensional echocardiography (2D-echo) and 3D-WMT in adult healthy population and to assess the intermethod, intra- and interobserver agreement. Prospective study. Nonselected healthy subjects were enrolled. Every patient underwent a 2D-echo and a 3D-WMT examination. 2D-echo right atrial volume was obtained by using the area-length method (A-L) from four- and two-chamber view. 3D-echo volumes were assessed by 3D-WMT. Values were indexed by the patient's body surface area. Sixty consecutive healthy subjects were enrolled. Mean age was 57 ± 12-years old and 27 patients (45%) were male. Average indexed right atrial volume obtained by 2D-echo and 3D-echo was 16.76 ± 8.15 mL/m(2) and 19.05 ± 6.87 mL/m(2) , respectively. Univariate linear regression analysis between 2D-echo and 3D-echo right atrial volumes shows a weak correlation between right atrial volume obtained with 2D-echo compared with 3D-WMT (r = 0.29, CI 95% 0.029-0.66, P = 0.033). The agreement analysis shows a similar result (intraclass correlation coefficient [ICC] = 0.28). The intra- and interobserver agreement analysis showed a better agreement when using 3D-WMT. This is the first study that reports the reference indexed right atrial volume values by means of 2D-echo and 3D-echo in healthy population. 3D-WMT is a feasible and reproducible method to determine right atrial volume.


Localization of human U1 small nuclear RNA genes to band p36.3 of chromosome 1 by in situ hybridization.
U1 small nuclear RNA (U1 snRNA) is encoded by a large family of genes (30-125 copies/haploid genome) which are transcribed by RNA polymerase II. U1 snRNA is thought to function in gene splicing. Since the U1 genes were found to be greater than 20 kb apart by analyzing genomic phage clones, the chromosomal location of U1 genes in the human genome was determined using Southern filter analysis of DNA isolated from human-rodent somatic cell hybrids and by in situ hybridization. Human DNA digested with PvuII and probed with a U1-specific probe, pD2, show several major hybridizing fragments. Of these, two human PvuII fragments of 1.4 kb and 2.4 kb had unique mobilities compared to mouse fragments. In a study of 19 cell hybrids, the human-specific U1 fragments segregated with the chromosome 1 markers peptidase C and adenylate kinase 2. All other chromosomes showed greater than or equal to 19% discordancy . An additional 13 karyotyped cell hybrids, analyzed by Southern filter analysis, confirmed the assignment of this class of U1 genes to chromosome 1. Additional digests with MspI and PstI indicated that most U1 genes are located on chromosome 1. To determine if the U1 RNAs are located predominantly at one site or dispersed over chromosome 1, a tritium-labeled U1 probe was hybridized in situ to metaphase chromosomes. The majority of the grains were at band 1p36 .3, suggesting that most of the U1 genes are located in this region.


Family size, the physical environment, and socioeconomic effects across the stature distribution.
A neglected area in historical stature studies is the relationship between stature and family size. Using robust statistics and a large 19th century data set, this study documents a positive relationship between stature and family size across the stature distribution. The relationship between material inequality and health is the subject of considerable debate, and there was a positive relationship between stature and wealth and an inverse relationship between stature and material inequality. After controlling for family size and wealth variables, the paper reports a positive relationship between the physical environment and stature.


Microendoscopy reveals positive correlation in multiscale length changes and variable sarcomere lengths across different regions of human muscle.
Sarcomere length is a key physiological parameter that affects muscle force output; however, our understanding of the scaling of human muscle from sarcomere to whole muscle is based primarily on cadaveric data. The aims of this study were to explore the in vivo relationship between passive fascicle length and passive sarcomere length at different muscle-tendon unit lengths and determine whether sarcomere and fascicle length relationships are the same in different regions of muscle. A microendoscopy needle probe capable of in vivo sarcomere imaging was inserted into a proximal location of the human tibialis anterior muscle at three different ankle positions [5° dorsiflexion, 5° plantar flexion (PF), and 15° PF] and one distal location at a constant ankle position (5° PF distal). Ultrasound imaging of tibialis anterior fascicles, centered on the location of the needle probe, was performed for each condition to estimate fascicle length. Sarcomere length and fascicle length increased with increasing muscle-tendon unit length, although the correlation between sarcomere length change and muscle fascicle length change was only moderate (r2 = 0.45). Passive sarcomere length was longer at the distal imaging site than the proximal site (P = 0.01). When sarcomere number was estimated from sarcomere length and fascicle length, there were fewer sarcomeres in the fibers of distal location than the proximal location (P = 0.01). These data demonstrate that fascicle length changes are representative of sarcomere length changes, although significant variability in sarcomere length exists within a muscle and sarcomere number per fiber is region-dependent.NEW & NOTEWORTHY Sarcomere and fascicle lengths were measured in vivo from human muscle to examine the relationship between the different scales of organization. Changes in fascicle length were moderately related to sarcomere length changes; however, sarcomere length and number per fiber varied from proximal to distal regions of the muscle. Differences in average sarcomere operating lengths across the muscle suggest potentially different stresses or strains experienced within different regions of muscle.


Bi-lineage inducible and immunoregulatory electrospun fibers scaffolds for synchronous regeneration of tendon-to-bone interface.
Facilitating regeneration of the tendon-to-bone interface can reduce the risk of postoperative retear after rotator cuff repair. Unfortunately, undesirable inflammatory responses following injury, difficulties in fibrocartilage regeneration, and bone loss in the surrounding area are major contributors to suboptimal tendon-bone healing. Thus, the development of biomaterials capable of regulating macrophage polarization to a favorable phenotype and promoting the synchronous regeneration of the tendon-to-bone interface is currently a top priority. Here, strontium-doped mesoporous bioglass nanoparticles (Sr-MBG) were synthesized through a modulated sol-gel method and Bi-lineage Inducible and Immunoregulatory Electrospun Fibers Scaffolds (BIIEFS) containing Sr-MBG were fabricated. The BIIEFS were biocompatible, showed sustained release of multiple types of bioactive ions, enhanced osteogenic and chondrogenic differentiation of mesenchymal stem cells (MSCs), and facilitated macrophage polarization towards the M2 phenotype in vitro. The implantation of BIIEFS at the torn rotator cuff resulted in greater numbers of M2 macrophages and the synchronous regeneration of tendon, fibrocartilage, and bone at the tendon-to-bone interface, leading to a significant improvement in the biomechanical strength of the supraspinatus tendon-humerus complexes. Our research offers a feasible strategy to fabricate immunoregulatory and multi-lineage inducible electrospun fibers scaffolds incorporating bioglass nanoparticles for the regeneration of soft-to-hard tissue interfaces.


Effects of the extraction method and chromatographic separation solvent in the antioxidant activity of different species of "espinheira-santa".
Bioactivity of "espinheira-santa" leaves can be evaluated through solvent purification processes. Species of the same genus may contain different compounds, which may be separated by conventional chromatography using different solvents. The extraction process also influences the contents of these compounds. In order to optimize the above process research is required on variables such as solvents, temperature and extraction time. The objective of this work was to evaluate the antioxidant activity (ABTS, DPPH and FRAP) of extracts and purified fractions from leaves of Maytenus ilicifolia and M. aquafolium. Percolation at 28 °C for 7 days, and ultrasound at 50, 60 and 70 °C for 15 min were the extraction methods tested. Open column chromatography (silica gel) was used in the fractionation of extracts, and hexane, chloroform and methanol were the elution solvents used. The evaluation methods of the antioxidant activity were DPPH, FRAP and ABTS. Plant species showed no significant differences between methods for DPPH, but the fractions obtained with chromatography had significant differences, the crude ethanolic extract (CEE) and the methanolic been in general superior. "espinheira-santa" is a plant with antioxidant potential, but the extraction methods are not optimal. Still, it can be said that the separation by chromatography provided a better visualization of the nature of the components of that plant that best stood out in relation to the antioxidant activity.


Intermittent theta burst stimulation over the parietal cortex has a significant neural effect on working memory.
The crucial role of the parietal cortex in working memory (WM) storage has been identified by fMRI studies. However, it remains unknown whether repeated parietal intermittent theta-burst stimulation (iTBS) can improve WM. In this within-subject randomized controlled study, under the guidance of fMRI-identified parietal activation in the left hemisphere, 22 healthy adults received real and sham iTBS sessions (five consecutive days, 600 pulses per day for each session) with an interval of 9 months between the two sessions. Electroencephalography signals of each subject before and after both iTBS sessions were collected during a change detection task. Changes in contralateral delay activity (CDA) and K-score were then calculated to reflect neural and behavioral WM improvement. Repeated-measures ANOVA suggested that real iTBS increased CDA more than the sham one (p = .011 for iTBS effect). Further analysis showed that this effect was more significant in the left hemisphere than in the right hemisphere (p = .029 for the hemisphere-by-iTBS interaction effect). Pearson correlation analyses showed significant correlations for two conditions between CDA changes in the left hemisphere and K score changes (ps <.05). In terms of the behavioral results, significant K score changes after real iTBS were observed for two conditions, but a repeated-measures ANOVA showed a nonsignificant main effect of iTBS (p = .826). These results indicate that the current iTBS protocol is a promising way to improve WM capability based on the neural indicator (CDA) but further optimization is needed to produce a behavioral effect.


Incidence of contrast-induced acute kidney injury in a large cohort of all-comers undergoing percutaneous coronary intervention: Comparison of five contrast media.
There is controversy as to whether iso-osmolar contrast media (IOCM) are associated with lower risk of contrast-induced acute kidney injury (CI-AKI), compared with low-osmolar contrast media (LOCM). We aimed to evaluate if a differential risk of CI-AKI exists after percutaneous coronary intervention (PCI) according to different contrast media (CM) types. We performed a single-center retrospective study in a cohort of all-comers undergoing PCI between January 2012 and December 2016. CI-AKI was defined as an increase in serum creatinine ≥0.3 mg/dl or ≥50% within 72 h from PCI. IOCM were represented by iodixanol, whereas four different LOCM were utilized (ioversol, iopromide, iomeprol, iobitridol). Multiple-treatment inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis was performed to identify whether CM type was an independent predictor of CI-AKI. We included 2648 subjects (ioversol, n = 272; iopromide, n = 818; iomeprol, n = 611; iobitridol, n = 460; iodixanol, n = 487). CI-AKI occurred in 300 patients (11.7%) overall, with no differences across CM groups (ioversol 13.0%, iopromide 11.5%, iomeprol 10.2%, iobitridol 13.9%, iodixanol 11.3%; p = 0.42). CI-AKI requiring dialysis was observed in 8 patients (0.3%) overall (p = 0.50). On IPTW-adjusted analysis, none of the LOCM was associated with a significantly different risk of CI-AKI compared with iodixanol: ioversol OR 0.986 (95% confidence interval [CI] 0.611-1.591), iopromide OR 0.870 (95% CI 0.606-1.250), iomeprol OR 0.904 (95% CI 0.619-1.319), iobitridol OR 1.258 (95% CI 0.850-1.861). In a large cohort of all-comers undergoing PCI, there were no differences in the adjusted risk of CI-AKI across 4 LOCM, compared with iodixanol.


Synthesis and structural characterization of high spin M/Cu (M = Mn, Fe) heterobimetallic and Fe/Cu2 trimetallic phosphinoamides.
The heterobimetallic complexes [Mn((i)PrNPPh(2))(3)Cu((i)PrNHPPh(2))] (1) and [Fe((i)PrNPPh(2))(3)Cu((i)PrNHPPh(2))] (2) have been synthesized by the one pot reaction of LiN(i)PrPPh(2), MCl(2) (M = Mn, Fe), and CuI in high yield. Addition of excess CuI into 2 or directly to the reaction mixture led to the formation of a heterotrimetallic [Fe((i)PrNPPh(2))(3)Cu(2)((i)PrNPPh(2))] (3) in good yield. Complexes 1-3 have been characterized by means of elemental analysis, paramagnetic (1)H NMR, UV-vis spectroscopy, cyclic voltammetry, and single crystal X-ray analysis. In all three complexes, Mn or Fe are in the +2 oxidation state and have a high spin electron configuration, as evidenced by solution Evans' method. In addition, the oxidation state of Fe in complex 3 is confirmed by zero-field (57)Fe Mössbauer spectroscopy. X-ray crystallography reveals that the three coordinate Mn/Fe centers in the zwitterionic complexes 1-3 adopt an unusual trigonal planar geometry.


[What is the utility of proton pump inhibitor testing in non-cardiac chest pain?].
Noncardiac chest pain (NCCP) often represents a diagnostic and therapeutic challenge. Given that gastroesophageal reflux disease (GERD) is the most common cause of NCCP, initial treatment with proton-pump inhibitors (PPI) has been proposed for all patients (PPI testing), reserving esophageal function testing solely for non-responders. The aim of the present study was to provide evidence on the clinical utility of PPI testing with high-dose pantoprazole in patients with NCCP. We carried out a study of diagnostic performance with a cohort design in patients with NCCP, who had been assessed by the Cardiology Service. All patients underwent upper endoscopy, esophageal manometry, and 24h esophageal pH monitoring before PPI testing with pantoprazole 40 mg every 12h for 1 month. Before and after treatment, we assessed the severity (intensity and frequency) of chest pain, quality of life, and anxiety and depression by means of specific questionnaires. The diagnosis of GERD was based on a pathological finding of esophageal pH monitoring. A positive response to PPI testing was defined as an improvement in chest pain >50% compared with the baseline score after 1 month of PPI therapy. We included 30 consecutive patients (17 men/13 women) with a mean age of 49 years. Of these 30 patients, 20 with NCCP had GERD (67%, 95%CI: 47%-83%). A positive response to PPI therapy was observed in 13 of the 30 (43%) patients with NCCP: 11 of the 20 (55%) patients in the GERD-positive group and 2 of the 10 (20%) in the GERD-negative group. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PPI testing was 55%, 80%, 85%, 47% and 63%, respectively. A significant reduction in chest pain after pantoprazole therapy (P=.003) and a slight non significant improvement in anxiety and depression was achieved in the GERD-positive group as compared to the GERD-negative group. In NCCP, PPI testing with pantoprazole has a low sensitivity for the diagnosis of GERD, placing in doubt the strategy of reserving functional study to non-responders to antisecretory therapy. Esophageal function testing and accurate diagnosis would allow appropriate targeted therapy for all patients with NCCP.


Anatomy and physiology of the right ventricle.
Under normal baseline conditions the unique anatomy, myocardial ultrastructure, and coronary physiology of the right ventricle (RV) reflect a high-volume low-pressure pump. Early work described the RV as a passive conduit with minimal pumping capability. It is now appreciated that through a mechanism of ventricular interdependence, RV systolic function and diastolic load are extremely important in the prognosis and treatment of congestive heart failure, cardiac transplantation, pulmonary hypertension, congenital heart disease, and left ventricle assist devices. Magnetic resonance imaging with three-dimensional analysis has shown the complex geometry of the RV and the interaction of both ventricles within the pericardium.


Economic impact of musculoskeletal disorders (MSDs) on work in Europe.
Musculoskeletal disorders (MSDs) are the leading cause of work disability, sickness absence from work, 'presenteeism' and loss of productivity across all the European Union (EU) member states. It is estimated that the total cost of lost productivity attributable to MSDs among people of working age in the EU could be as high as 2% of gross domestic product (GDP). This paper examines the available evidence on the economic burden of MSDs on work across Europe and highlights areas of policy, clinical and employment practice which might improve work outcomes for individuals and families and reduce the economic and social costs of MSDs.


Phototunable interpenetrating polymer network hydrogels to stimulate the vasculogenesis of stem cell-derived endothelial progenitors.
Vascularization of engineered scaffolds remains a critical obstacle hindering the translation of tissue engineering from the bench to the clinic. We previously demonstrated the robust micro-vascularization of collagen hydrogels with induced pluripotent stem cell (iPSC)-derived endothelial progenitors; however, physically cross-linked collagen hydrogels compact rapidly and exhibit limited strength. We have synthesized an interpenetrating polymer network (IPN) hydrogel comprised of collagen and norbornene-modified hyaluronic acid (NorHA) to address these challenges. This dual-network hydrogel combines the natural cues presented by collagen's binding sites and extracellular matrix (ECM)-mimicking fibrous architecture with the in situ modularity and chemical cross-linking of NorHA. We modulated the IPN hydrogel's stiffness and degradability by varying the concentration and sequence, respectively, of the NorHA peptide cross-linker. Rheological characterization of the photo-mediated gelation process revealed that the IPN hydrogel's stiffness increased with cross-linker concentration and was decoupled from the bulk NorHA content. Conversely, the swelling of the IPN hydrogel decreased linearly with increasing cross-linker concentration. Collagen microarchitecture remained relatively unchanged across cross-linking conditions, although the addition of NorHA delayed collagen fibrillogenesis. Upon iPSC-derived endothelial progenitor encapsulation, robust, lumenized microvascular networks developed in IPN hydrogels over two weeks. Subsequent computational analysis showed that an initial rise in stiffness increased the number of branch points and vessels, but vascular growth was suppressed in high stiffness IPN hydrogels. These results suggest that an IPN hydrogel consisting of collagen and NorHA is highly tunable, compaction resistant, and capable of supporting vasculogenesis.


Projections to the superior colliculus from the dorsal hypothalamic area and other prosencephalic structures derived from the embryonic subthalamic longitudinal band of the diencephalon.
After injections of an aqueous solution of horseradish peroxidase (HRP) restricted to the superior colliculus of the cat, labeled neurons were found ipsilaterally in the dorsal hypothalamic area, lateral hypothalamus, zone incerta, reticular thalamic nucleus and ventral lateral geniculate. In most cases labeled neurons were observed in the same structures of the contralateral side. Some scattered neurons were observed in other hypothalamic structures and the globus pallidus. Most of these prosencephalic formations are subthalamic derivatives, thus having a common embryologic origin.


Associations between COVID-19 lockdown and post-lockdown on the mental health of pregnant women, postpartum women and their partners from the Queensland family cohort prospective study.
There are very few developed countries where physical isolation and low community transmission has been reported for COVID-19 but this has been the experience of Australia. The impact of physical isolation combined with low disease transmission on the mental health of pregnant women is currently unknown and there have been no studies examining the psychological experience for partners of pregnant women during lockdown. The aim of the current study was to examine the impact of the first COVID-19 lockdown in March 2020 and post lockdown from August 2020 on the mental health of pregnant women or postpartum women and their partners. Pregnant women and their partners were prospectively recruited to the study before 24 weeks gestation and completed various questionnaires related to mental health and general wellbeing at 24 weeks gestation and then again at 6 weeks postpartum. The Depression, Anxiety and Stress Scale (DASS-21) and the Edinburgh Postnatal Depression Scale (EPDS) were used as outcome measures for the assessment of mental health in women and DASS-21 was administered to their partners. This analysis encompasses 3 time points where families were recruited; before the pandemic (Aug 2018-Feb 2020), during lockdown (Mar-Aug 2020) and after the first lockdown was over (Sept-Dec 2020). There was no significant effect of COVID-19 lockdown and post lockdown on depression or postnatal depression in women when compared to a pre-COVID-19 subgroup. The odds of pregnant women or postpartum women experiencing severe anxiety was more than halved in women during lockdown relative to women in the pre-COVID-19 period (OR = 0.47; 95%CI: 0.27-0.81; P = 0.006). Following lockdown severe anxiety was comparable to the pre-COVID-19 women. Lockdown did not have any substantial effects on stress scores for pregnant and postpartum women. However, a substantial decrease of over 70% in the odds of severe stress was observed post-lockdown relative to pre-COVID-19 levels. Partner's depression, anxiety and stress did not change significantly with lockdown or post lockdown. A reproductive age population appear to be able to manage the impact of lockdown and the pandemic with some benefits related to reduced anxiety.


Serum ceruloplasmin as cancer marker in oral pre-cancers and cancers.
Oxidative stress leads to a compensatory increase in levels of serum ceruloplasmin in patients with such imbalances. Greater than normal serum ceruloplasmin levels are noticed in numerous cancers including the leukemias and Hodgkin's lymphoma. The purpose of the present study was to estimate and evaluate the efficacy of serum ceruloplasmin levels as a potential biomarker in the early detection of oral potentially malignant epithelial lesions (PMELs) including leukoplakia, oral submucous fibrosis (OSMF), and oral squamous cell carcinoma (OSCC) patients. The present observational study was conducted over a period of 2 years wherein 100 subjects aged between 18 to 60 years were divided into four groups with Group A consisting of 25 healthy controls, Group B and C with 25 patients each, clinically diagnosed with oral leukoplakia and OSMF and Group D with 25 patients clinically diagnosed and histopathologically proven OSCC. The patients were subjected to incisional biopsy after routine hematological investigation while the same sera samples were used for analysis of serum ceruloplasmin levels. Comparison of serum ceruloplasmin levels between the groups was performed using one way analysis of variance (one way ANOVA) test while P < 0.05 was considered statistically significant. The mean serum ceruloplasmin levels were found to be 43.19 ± 1.90mg/dl in subjects of group A, 47.68 ± 1.51mg/dl in group B, 47.74 ± 1.45mg/dl in group C and 47.73 ± 0.74mg/dl in group D. Using one-way ANOVA, statistically significant variations were found in the values of mean serum ceruloplasmin levels in subjects of the four groups (F-value = 59.58, P = 0.0001). The observations of the present study revealed that serum ceruloplasmin levels were found to be raised in all 3 study groups including oral leukoplakia, OSMF and OSCC as compared to the controls while the results were found to be statistically significant.


Complement deficiency and disease: an update.
Complement deficiencies are probably vastly under-diagnosed within clinical medicine. Judging from a Swedish study of C2 deficiency, a deficiency with an estimated prevalence of about 1/20,000 in Western countries, less than 10% of the deficiencies of the classical and alternative pathways and the late complement components are identified in Sweden. C1 inhibitor deficiency and deficiencies of MBL and MASP-2 were not included in the assessment. The introduction of new screening methods should facilitate detection of complement deficiencies in clinical practice. In our study of C2 deficiency (n=40), 57% of the patients had a history of invasive infection with encapsulated bacteria, mainly Streptococcus pneumoniae. This emphasizes the importance of the classical and/or the lectin pathway in defence against severe infection. Rheumatological disease, mainly systemic lupus erythematosus was present in 43% of the patients. In addition, a significant association was found between C2 deficiency and atherosclerosis. Complement-dependent disease mechanisms are discussed together with the potential importance of non-complement genes for disease expression in complement deficiencies. Analysis of larger patient groups is required in order to establish guidelines for investigation and treatment of patients with complement deficiency.


The Posterior Cingulate Cortex Reflects the Impact of Anxiety on Drift Rates During Cognitive Processing.
Generally, anxiety is thought to impair ongoing cognitive operations. Surprisingly, however, anxiety has been shown to improve performance during the Go/NoGo task. Understanding how anxiety can facilitate task performance may shed light on avenues to address the cognitive deficits commonly associated with anxiety. A total of 39 participants (mean age ± SD = 27.5 ± 7.22 years; 18 women) performed a Go/NoGo task during periods of safety and periods of experimental anxiety, induced using the unpredictable delivery of aversive stimuli. Computational analysis and ultrahigh field (7T) functional magnetic resonance imaging were used to determine how induced anxiety affected computational processes and blood oxygen level-dependent responses during the task. Induced anxiety improved accuracy during the Go/NoGo task. Induced anxiety was associated with an amplified drift rate process, which is thought to reflect increased informational uptake. In addition, changes in drift rate during the anxiety condition were associated with enhanced blood oxygen level-dependent responses within the posterior cingulate cortex during Go trials. These results may reflect the impact of induced anxiety on the activity of neurons within the posterior cingulate cortex, whose activity patterns mimic the buildup of evidence accumulation. Collectively, these results shed light on the mechanisms underlying facilitated task performance and suggest that anxiety can improve cognitive processing by enhancing information uptake and increasing activity within the posterior cingulate cortex.


Long-term outcome of esophageal mucosal squamous cell carcinoma without lymphovascular involvement after endoscopic resection.
Esophageal cancer is an aggressive cancer with a reported 3-year survival of 20%. However, early-stage esophageal cancer can be cured by endoscopic resection (ER). The long-term survival of esophageal mucosal squamous cell carcinoma after ER was investigated by calculating the standard mortality rate (SMR). From January 1995 to December 2004, 110 patients with 138 esophageal mucosal squamous cell carcinomas without lymphovascular involvement were treated by ER. Long-term survival after ER was compared with that in the general population by calculating SMR. Subgroup analysis of patients without second primary cancer diagnosed within 1 year before ER (subgroup A) was also performed. A total of 108 patients (98.2%) were followed-up completely, with a mean observation period of 4.7 (0.4-11.3) years. The cumulative 5-year survival rate of all patients and subgroup A was 79.5% and 86.6%, respectively. Overall mortality (SMR, 1.68; 95% confidence interval [CI], 1.05-2.55) and mortality from malignant tumor (SMR, 3.14; 95% CI, 1.79-5.09) was significantly higher than that in the general population. SMR of esophageal cancer was high, although it was not significantly different from that in the general population (SMR, 4.82; 95% CI, 0.06-26.81). In subgroup A overall mortality (SMR, 0.86; 95% CI, 0.41-1.57) was similar to that in the general population. High overall mortality in patients with esophageal mucosal cancer after ER was mainly due to elevated mortality from second primary cancer. Favorable mortality in subgroup A indicates the efficiency of ER as a curative treatment for esophageal mucosal cancer.


Poly(vinyl alcohol)/sodium alginate polymer membranes as eco-friendly and biodegradable coatings for slow release fertilizers.
The use of slow release fertilizers (SRFs) is an effective approach for reducing agriculture cost, environmental and ecological issues simultaneously. The present study provides a series of poly(vinyl alcohol) (PVA)/sodium alginate (SA) polymer membranes as eco-friendly and biodegradable coatings for SRFs. Moreover, polymer-coated urea (PCU) granules were fabricated through coating the urea granules with the resulting membranes. Our first interest was to fabricate three membranes (PS1, PS2, PS3) of different PVA/SA weight ratios (9:1, 8:2, 7:3) using glutaraldehyde as a crosslinking agent, and crosslink the PS3 membrane with a CaCl2 solution further to obtain the PC3 membrane. The chemical properties and morphologies of the membranes were characterized. Second, the nitrogen release behavior of the PCU granules was measured and calculated, respectively. Crosslinking with glutaraldehyde made the PS1, PS2, PS3 membranes uniform and compact, whereas crosslinking with a CaCl2 solution formed an 'egg box' structure inside the PC3 membrane. PS3 membrane with the minimum PVA/SA weight ratio had the highest hydrophily (water uptake: 106.25%, water contact angle: 55.1o ), whereas PC3 membrane had the lowest hydrophily (water uptake: 21.57%, water contact angle: 67.3o ). The biodegradation ratios of the membranes were in the range 44-60% in 90 days, indicating that they had excellent biodegradability. The measured fractional release on the day 30 of the PCU granules ranged from 89.33% to 97.07%. The calculated nitrogen release behavior agreed well with the measured values. The resulting eco-friendly and biodegradable PVA/SA membranes are alternative coatings for SRFs. © 2022 Society of Chemical Industry.


[Spyridon Kanellis, a 19th century daring plagiarist].
In 1883, a case of daring plagiarism was revealed during a session of the Biology Society in Paris. This article discusses the details of this plagiarism and the identity of its perpetrator, a physician by the name of Spiridion Kanellis.


Color-Doppler US features of a pyogenic granuloma of the upper dorsum tongue.
The diagnosis of oral lesions is based on clinical history, clinical examination and imaging exams. Different imaging modalities are available for the diagnosis and follow-up of these lesions such as computed tomography, magnetic resonance imaging, color-Doppler ultrasound, angiography and positron emission tomography. To date, color-Doppler ultrasound is considered the first-line imaging approach since it provides a non-invasive, cost-effective, real-time evaluation of oral anomalies. It provides both morphological and vascular information which are useful to determine the best therapeutic options. Differential diagnosis of a bleeding lobular mass of the tongue is, however, not always easy and includes several vascular and non-vascular lesions. We present herein a case of pyogenic granuloma of the tongue that at Color-Doppler US appeared as hypervascular lesion.


Incorporation and validation of clinically relevant performance metrics of simulation (CRPMS) into a novel full-immersion simulation platform for nerve-sparing robot-assisted radical prostatectomy (NS-RARP) utilizing three-dimensional printing and hydrogel casting technology.
To incorporate and validate clinically relevant performance metrics of simulation (CRPMS) into a hydrogel model for nerve-sparing robot-assisted radical prostatectomy (NS-RARP). Anatomically accurate models of the human pelvis, bladder, prostate, urethra, neurovascular bundle (NVB) and relevant adjacent structures were created from patient MRI by injecting polyvinyl alcohol (PVA) hydrogels into three-dimensionally printed injection molds. The following steps of NS-RARP were simulated: bladder neck dissection; seminal vesicle mobilization; NVB dissection; and urethrovesical anastomosis (UVA). Five experts (caseload >500) and nine novices (caseload <50) completed the simulation. Force applied to the NVB during the dissection was quantified by a novel tension wire sensor system fabricated into the NVB. Post-simulation margin status (assessed by induction of chemiluminescent reaction with fluorescent dye mixed into the prostate PVA) and UVA weathertightness (via a standard 180-mL leak test) were also assessed. Objective scoring, using Global Evaluative Assessment of Robotic Skills (GEARS) and Robotic Anastomosis Competency Evaluation (RACE), was performed by two blinded surgeons. GEARS scores were correlated with forces applied to the NVB, and RACE scores were correlated with UVA leak rates. The expert group achieved faster task-specific times for nerve-sparing (P = 0.007) and superior surgical margin results (P = 0.011). Nerve forces applied were significantly lower for the expert group with regard to maximum force (P = 0.011), average force (P = 0.011), peak frequency (P = 0.027) and total energy (P = 0.003). Higher force sensitivity (subcategory of GEARS score) and total GEARS score correlated with lower nerve forces (total energy in Joules) applied to NVB during the simulation with a correlation coefficient (r value) of -0.66 (P = 0.019) and -0.87 (P = 0.000), respectively. Both total and force sensitivity GEARS scores were significantly higher in the expert group compared to the novice group (P = 0.003). UVA leak rate highly correlated with total RACE score r value = -0.86 (P = 0.000). Mean RACE scores were also significantly different between novices and experts (P = 0.003). We present a realistic, feedback-driven, full-immersion simulation platform for the development and evaluation of surgical skills pertinent to NS-RARP. The correlation of validated objective metrics (GEARS and RACE) with our CRPMS suggests their application as a novel method for real-time assessment and feedback during robotic surgery training. Further work is required to assess the ability to predict live surgical outcomes.


Ethanol rapidly induces steroidogenic acute regulatory protein expression and translocation in rat adrenal gland.
Acute ethanol exposure increases GABAergic neuroactive steroids in plasma and brain by releasing these steroids or their precursors from the adrenal glands. The present study showed that ethanol administration rapidly increases the expression of steroidogenic acute regulatory protein (StAR) in the cytosolic and mitochondrial fractions of adrenal glands. The increased StAR protein expression paralleled increases in plasma pregnenolone, progesterone and corticosterone levels. The rapid synthesis and translocation of StAR protein in adrenals likely represent the mechanism of ethanol-induced increases in neuroactive steroids.


[Study on genetic phenotype of asthma through examination of neonates' cord blood cells and interleukin-4].
To identify the genetic phenotypes of asthma based on the examination of the umbilical cord blood from neonates of the mothers with asthma. Umbilical cord blood was collected from 39 asthmatic lying-in women and 46 healthy lying-in women. Eosinophils and basophils absolute counts, total immunoglobulin E, and interleukin (IL)-4 were examined. Mononuclear cells (MNCs) from the umbilical cord blood were cultured. IL-4 in the supernatant was test by ELISA. White cells were collected from the umbilical cord blood. Basophils and T lymphocytes were purified, cultured, and stimulated by hyper osmotic mannitol. RT-PCR was used to test the mRNA expression of IL-4 in the supernatant. There were no significant differences in the counts of basophils and eosinophils, total IgE, and IL-4 in the cord blood, and IL-4 in the supernatant of cultured MNCs. After stimulation of hyper-osmotic mannitol, equine anti-human IgE, and dust mite the HBDT positive rates were 64.10%, 17.95%, and 0% respectively in the neonates of asthmatic women group, the former two rates being both significantly higher than those in the neonates of healthy women group (15.22% and 2.17% respectively, P < 0.05 and P < 0.025). After stimulation of hyper-osmotic mannitol, IL-4 mRNA was markedly expressed in the purified basophils of both groups and was almost not expressed in the purified eosinophils of both groups. There is qualitative abnormalities in the basophils from the cord blood of neonates of asthmatic mothers that strongly express IL-4 mRNA. Such characteristics may be an asthma-related genetic phenotype.


Ether lysophospholipid-induced production of platelet-activating factor in human polymorphonuclear leukocytes.
Human polymorphonuclear leukocytes (PMN) produced considerable amounts of platelet-activating factor (PAF) when exposed to various concentrations of lyso-PAF, especially in the absence of albumin. The amount of produced PAF in the presence of 5 microM lyso-PAF (without albumin) was 1.1 pmol/10 min per 2.5 X 10(6) cells, which was close to the level in the case of opsonized zymosan stimulation. We found that the activity of neither acetyltransferase nor acetylhydrolase was affected markedly by the treatment of cells with lyso-PAF, suggesting that the increased availability of lyso-PAF could be responsible for the induction of PAF synthesis. We also found that PAF synthesis was induced not only by lyso-PAF but also by ether-containing ethanolamine lysophospholipids, 1-alkenyl(alkyl)-sn-glycero-3-phosphoethanolamine (GPE). The addition of 1-alkenyl(alkyl)-GPE caused the degradation of pre-existing 1-alkyl-2-arachidonoyl-sn-glycero-3-phosphocholine (GPC) and an increased level of lyso-PAF, followed by the formation of PAF. By contrast, 1-acyl-GPC and 1-acyl-GPE failed to induce PAF production. These results suggest a possible key role of the availability of lyso-PAF in triggering the biosynthesis of PAF in human PMN.


Investigation of the loss of byssus in Mytilus galloprovincialis from mussel farms in the Adriatic Sea.
A fungal infection has been found in the mussel Mytilus galloprovincialis from Adriatic Sea mussel farms. The infection ultimately results in the loss of the byssus, with serious consequences for mussel farming yield. The pathogen provokes the progressive destruction of the foot muscles, also damaging related structures such as the intra-organism part of the byssus apparatus, resulting in loss of the thread component. The affected health status of the animal is also sustained by modifications in the digestive gland structure, ranging from hyperactivity to extreme cell death in the tubula. At present, the identity of the harmful fungus is unknown.


Item strength affects working memory capacity.
Do the processing and online manipulation of stimuli that are less familiar require more working memory (WM) resources? Is it more difficult to solve demanding problems when the symbols involved are less rather than more familiar? We explored these questions with a dual-task paradigm in which subjects had to solve algebra problems of different complexities while simultaneously holding novel symbol-digit associations in WM. The symbols were previously unknown Chinese characters, whose familiarity was manipulated by differential training frequency with a visual search task for nine hour-long sessions over 3 weeks. Subsequently, subjects solved equations that required one or two transformations. Before each trial, two different integers were assigned to two different Chinese characters of the same training frequency. Half of the time, those characters were present as variables in the equation and had to be substituted for the corresponding digits. After attempting to solve the equation, subjects had to recognize which two characters were shown immediately before that trial and to recall the integer associated with each. Solution accuracy and response times were better when the problems required one transformation only; variable substitution was not required; or the Chinese characters were high frequency. The effects of stimulus familiarity increased as the WM demands of the equation increased. Character-digit associations were also recalled less well with low-frequency characters. These results provide strong support that WM capacity depends not only on the number of chunks of information one is attempting to process but also on their strength or familiarity.


Gene delivery to human sweat glands: a model for cystic fibrosis gene therapy.
Gene therapy vectors are mostly studied in cultured cells, rodents, and sometimes in non-human primates, but it is useful to test them in human tissue prior to clinical trials. In this study, we investigated the possibility of using human sweat glands as a model for testing cystic fibrosis (CF) gene therapy vectors. Human sweat glands are relatively easy to obtain from skin biopsy, and can be tested for CFTR function. Using patients' sweat glands could provide a safe model to study the efficacy of CF gene therapy. As the first step to explore using sweat glands as a model for CF gene therapy, we examined various ex vivo gene delivery methods for a helper-dependent adenovirus (HD-Ad) vector. Gene delivery to sweat glands in skin organ culture was studied by topical application, intradermal injection or submerged culture. We found that transduction efficiency can be enhanced by pretreating isolated sweat glands with dispase, which suggests that the basement membrane is a critical barrier to gene delivery by adenoviral vectors. Using this approach, we showed that Cftr could be efficiently delivered to and expressed by the epithelial cells of sweat glands with our helper-dependent adenoviral vector containing cytokeratin 18 regulatory elements. Based on this study we propose that sweat glands might be used as an alternative model to study CF gene therapy in humans.


Effect of different doses of progestin on uterine leiomyomas in postmenopausal women.
To evaluate the effects of two doses of medroxyprogesterone acetate (MPA) on uterine leiomyoma sizes and on uterine bleeding pattern in postmenopausal women treated with oral hormone replacement therapy (HRT). Thirty natural postmenopausal women affected by uterine leiomyomas were enrolled and treated with oral micronized estradiol (E(2)) at dose of 2 mg per day, and randomized to receive in association MPA at dose of 2.5 mg daily (group A) or of 5 mg daily (group B). At the beginning of the study and after 1 year of treatment, uterine leiomyomata dimensions were measured using transvaginal ultrasonography (TV-USG). The subjects were instructed to note on a daily dairy the number and severity of abnormal uterine bleeding (AUB) episodes. After 1 year of therapy, a significant changes in mean uterine leiomyomas size was observed in the group treated with higher dose of MPA. No significant differences in uterine bleeding were detected between the two groups. In postmenopausal women with uterine leiomyomas, it is necessary to use the minimal efficacious dose of progestin during HRT because of a higher risk to increase the tumors dimensions.


Relationship between online social support and adolescents' mental health: A systematic review and meta-analysis.
The potential benefits of supportive interactions on social networking sites on adolescents' mental health are promising; however, no systematic evaluation has been conducted on this topic. This review examined empirical research on the relationship between social support derived from social networking sites and adolescents' mental health both theoretically and empirically. Followed PRISMA guidelines, we conducted a systematic literature search on six English and three Chinese databases in February 2020. Four thousand one hundred and seventy-seven articles were screened first by title, then abstract, and lastly, full articles. Fourteen studies (five English and nine Chinese) were identified, with total sample of 11,616 adolescents (age: 10-19 years; females: 42.7%-56.3%). Meta-analysis showed that the correlation of online social support with self-esteem was moderate and significant (r = .29), but with depression was small and insignificant (r = -.09). Sensitivity analysis indicated that social support from acquaintances on the internet may not be as beneficial as from real-life acquaintances. Despite that there isn't enough research on other specific mental health outcomes to run a quantitative synthesis, individual studies suggest that online social support (OSS) may be associated with increased self-identity and life satisfaction, decreased loneliness and social anxiety, it also counteracts the negative effect of stress and cyberbullying on mental health. OSS might be beneficial for adolescents' mental health, especially self-esteem, although the causal relationship requires longitudinal studies to confirm, and the underlying mechanisms need further investigation.


Observations on avian pasteurellosis in Britain.
An investigation into the extent and significance of Pasteurella multocida infections of birds and poultry in Britain during a three year period (1974--1977) was undertaken. This was achieved by means of postal questionnaires, coupled with the biochemical and serological examination of bacterial isolates from 91 outbreaks in poultry and from nine cases in other avian species.


Narcolepsy in children and young people in Ireland: 2006-2017.
To describe the population of young people in Ireland diagnosed with narcolepsy with regards to vaccine exposure, symptomatology, investigation results and experience of medical treatment. Retrospective review of medical records at the single tertiary referral centre for young people with narcolepsy in Ireland. Sixty-seven patients were diagnosed with narcolepsy between July 2006 and July 2017. Sixty-one (91%) of these developed symptoms after receiving the Pandemrix vaccine. The population was largely homogeneous with low hypocretin (87.5%), HLA DQB1∗0602 positivity (95%) and unremarkable findings on MRI Brain (100%). 77.6% experienced cataplexy; we also measured high levels of obesity, school non-attendance and psychosocial complexity. Symptoms often continued despite treatment, with multiple medications prescribed in 76.1% of patients. Prescription of sodium oxybate was associated with a significant reduction in BMI standard deviation scores at 6 months, with improved IOTF obesity scores seen at 36 month follow-up. This paper describes the experience of narcolepsy in children and young people in Ireland from 2006 - 2017 at the national tertiary referral centre. Narcolepsy in children and young people in Ireland carries a significant burden of illness, with impact on participation in education as well as physical and mental health. Symptoms can be refractory to medical treatment. Referral to tertiary centres for prompt treatment and multidisciplinary input is essential.