Particulate matter pollution and the COVID-19 outbreak: results from Italian regions and provinces.
Particulate matter exposure has been associated with the appearance and severity of several diseases, including viral infections. The aim of this study was to investigate whether coronavirus disease 2019 (COVID-19) cases and deaths across Italian regions and provinces in March 2020 were linked to past exposure to fine and coarse particulate matter (namely, PM2.5 and PM10, respectively). Geographical distributions of COVID-19 cases and deaths (105,792 and 12,428, respectively, up to 31st March 2020), PM2.5 and PM10 exposure, and demographic characteristics were extracted from publicly accessible databases. Adjusted regression models were performed to test the association between particulate matter exposure in different Italian regions and provinces and COVID-19 incidence proportions and death rates. A heterogeneous distribution of COVID-19 cases/deaths and particulate matter exposure was observed in Italy, with the highest numbers in Northern Italy regions and provinces. Independent associations between regional PM2.5/PM10 exposure and COVID-19 incidence proportion and death rate were observed (COVID-19 incidence proportion: β = 0.71, p = 0.003, β = 0.61, p = 0.031, respectively; COVID-19 death rate: β = 0.68, p = 0.004 and β = 0.61, p = 0.029, respectively). Similarly, PM2.5/PM10 exposures were independently associated with COVID-19 incidence proportion (β = 0.26, p = 0.024 and β = 0.27, p = 0.006, respectively) at the provincial level. The number of days exceeding the provincial limit value of exposure to PM10 (50 µg/m3) was also independently associated with the COVID-19 incidence proportion (β = 0.30, p = 0.008). Exposure to PM2.5 and PM10 is associated with COVID-19 cases and deaths, suggesting that particulate matter pollution may play a role in the COVID-19 outbreak and explain the heterogeneous distribution of COVID-19 in Italian regions and provinces.


CRISPR/Cas-based screening of long non-coding RNAs (lncRNAs) in macrophages with an NF-κB reporter.
The innate immune system protects against infections by initiating an inducible inflammatory response. NF-κB is one of the critical transcription factors controlling this complex response, but some aspects of its regulation remain unclear. For example, although long non-coding RNAs (lncRNAs) have been shown to critically regulate gene expression, only a fraction of these have been functionally characterized, and the extent to which lncRNAs control NF-κB expression is unknown. Here, we describe the generation of a GFP-based NF-κB reporter system in immortalized murine bone marrow-derived macrophages (iBMDM). Activation of this reporter, using Toll-like receptor ligands, resulted in GFP expression, which could be monitored by flow cytometry. We also established a CRISPR/Cas9 gene deletion system in this NF-κB reporter line, enabling us to screen for genes that regulate NF-κB signaling. Our deletion-based approach identified two long intergenic non-coding(linc)RNAs, lincRNA-Cox2 and lincRNA-AK170409, that control NF-κB signaling. We demonstrate a potential novel role for lincRNA-Cox2 in promoting IκBα degradation in the cytoplasm. For lincRNA-AK170409, we provide evidence that this nuclearly-localized lincRNA regulates a number of inflammation-related genes. In conclusion, we have established an NF-κB-GFP iBMDM reporter cell line and a line that stably expresses Cas9. Our approach enabled the identification of lincRNA-Cox2 and lincRNA-AK170409 as NF-κB regulators, and this tool will be useful for identifying additional genes involved in regulating this transcription factor critical for immune function.


Pulmonary effects of continuous endotoxin infusion in the rat.
A major hindrance to the elucidation of the pathogenesis of the adult respiratory distress syndrome (ARDS) is the lack of an animal model consistent with the clinical course in humans. A continuous intravenous infusion of endotoxin (LPS) over a several day period was used to more closely parallel the clinical setting. Male Sprague-Dawley rats infused with LPS via indwelling right atrial catheters become tachypneic, lethargic and anorectic with a steady loss in body weight. Serial blood gas analyses demonstrate an early respiratory alkalosis followed by increasing acidosis and hypoxia. Lungs demonstrate 1) pulmonary leukoaggregation, 2) interstitial and intraalveolar edema, 3) Type I pneumocyte injury, 4) proliferation of Type II pneumocytes, and 5) thickening of the microvascular walls. Differential neutrophil count in bronchoalveolar lavage (BAL) fluid increased from 1% to a peak of 59.1% +/- 3.0% and protein content was elevated. A prolonged infusion of LPS in the rat produces a lung injury which mimics many of the pathophysiologic and histologic features associated with sepsis-induced ARDS in humans.


RNA-dependent synthesis of ergosteryl-3β-O-glycine in Ascomycota expands the diversity of steryl-amino acids.
A wide range of bacteria possess virulence factors such as aminoacyl-tRNA transferases (ATTs) that are capable of rerouting aminoacyl-transfer RNAs away from protein synthesis to conjugate amino acids onto glycerolipids. We recently showed that, although these pathways were thought to be restricted to bacteria, higher fungi also possess ergosteryl-3β-O-L-aspartate synthases (ErdSs), which transfer the L-Asp moiety of aspartyl-tRNAAsp onto the 3β-OH group of ergosterol (Erg), yielding ergosteryl-3β-O-L-aspartate (Erg-Asp). Here, we report the discovery, in fungi, of a second type of fungal sterol-specific ATTs, namely, ergosteryl-3β-O-glycine (Erg-Gly) synthase (ErgS). ErgS consists of a freestanding DUF2156 domain encoded by a gene distinct from and paralogous to that of ErdS. We show that the enzyme only uses Gly-tRNAGly produced by an independent glycyl-tRNA synthetase (GlyRS) to transfer glycine onto the 3β-OH of Erg, producing Erg-Gly. Phylogenomics analysis also show that the Erg-Gly synthesis pathway exists only in Ascomycota, including species of biotechnological interest, and more importantly, in human pathogens, such as Aspergillus fumigatus. The discovery of a second type of Erg-aa not only expands the repertoire of this particular class of fungal lipids but suggests that Erg-aa synthases might constitute a genuine subfamily of lipid-modifying ATTs.


Skeletal muscle characteristics predict body fat gain in response to overfeeding in never-obese young men.
The associations between skeletal muscle morphological and metabolic properties and the changes in body composition and metabolic rates in response to long-term overfeeding were investigated in 24 healthy young male identical twins (12 pairs). The proportions of muscle fiber types (type I, type IIA, and type IIB) and the activities of creatine kinase (CK), oxoglutarate dehydrogenase (OGDH), and phosphofructokinase (PFK) were determined from biopsies of the vastus lateralis before and after the overfeeding protocol. Body weight, fat mass (FM), fat-free mass (FFM), percent body fat (%FAT), resting metabolic rate (RMR), and thermic effect of a standardized meal (TEM) were also measured before and after 100 days of overfeeding. Type I muscle fiber proportions correlated inversely with the changes of FM and %FAT (r = -0.43, P =.035; r = -0.49, P =.01), and type IIA positively with the same overfeeding-induced changes (r = 0.43, P =.035; r = 0.47, P =.021). Baseline CK and PFK activities correlated negatively with the changes of RMR (r = -0.49, P =.017; r = -0.53, P =.01). OGDH activity at baseline correlated negatively with the changes of FM (r = -0.47, P = 0.02) but the ratio of PFK/OGDH correlated positively with the change of FM (r = 0.46, P =.02). We conclude that overfeeding induced a lower gain of FM in individuals with higher proportions of type I fiber, lower proportions of type IIA fiber, and higher OGDH activities at baseline. CK and PFK activities at baseline were associated with an attenuated increase in RMR when challenged by overfeeding. The significant correlations range from 0.43 to 0.53, and account for 18% to 28% of the variance in the response to overfeeding. The results suggest that an elevated skeletal muscle oxidative capacity plays a protective role in the response to long-term positive energy balance.


Sports Nutrition: Diets, Selection Factors, Recommendations.
An athlete's diet is influenced by external and internal factors that can reduce or exacerbate exercise-induced food intolerance/allergy symptoms. This review highlights many factors that influence food choices. However, it is important to remember that these food choices are dynamic, and their effectiveness varies with the time, location, and environmental factors in which the athlete chooses the food. Therefore, before training and competition, athletes should follow the recommendations of physicians and nutritionists. It is important to study and understand the nutritional strategies and trends that athletes use before and during training or competitions. This will identify future clinical trials that can be conducted to identify specific foods that athletes can consume to minimize negative symptoms associated with their consumption and optimize training outcomes.


The impact of total enteral nutrition on distraction osteogenesis in a rat model.
Limb lengthening by gradual mechanical distraction, termed distraction osteogenesis (DO), results in new bone formation. We have developed a rat tibial model for DO and have proceeded to study the effects of nutrition on this process. We have combined the intragastric diet delivery system of total enteral nutrition (TEN) with DO in the rat model. The first study was designed to address the weight loss associated with DO in dogs and patients. Rats in the chow + DO group lost 10% body weight over the 20-day distraction period but gradually gained weight back to the preoperative level by the end of the 5th week of the bone consolidation period. In contrast, in the TEN + DO group, a weight gain was recorded during the 20-day distraction phase. A second study was conducted to determine the effects of TEN on the rate and histology of regenerate bone formation. The weight changes replicated those seen in the first study. Standardized radiographs, taken on day 20, revealed increases (p < 0.003) in regenerate bone formation in the TEN group when compared with the chow group. Increased numbers of osteoclasts in the TEN group may indicate an accelerated entry into the remodeling phase of consolidation. Serum IGF-I values, taken at day 20, did not differ between the groups. These results demonstrate that the nutritional support dramatically increased the mineralized bone formed over the 20-day distraction period.


Robot-Assisted Laparoscopic Adenomyomectomy for Patients Who Want to Preserve Fertility.
An adenomyomectomy is a conservative-surgical option for preserving fertility. Conventional laparoscopic adenomyomectomies present difficulties in adenomyoma removal and suturing of the remaining myometrium. Robot-assisted laparoscopic surgery could overcome the limitations of conventional laparoscopic surgery. Four patients with severe secondary dysmenorrhea and pelvic pain visited Seoul St. Mary's Hospital and were diagnosed with adenomyosis by pelvic ultrasonography and pelvic magnetic resonance imaging (MRI). The four patients were unmarried, nulliparous women, who desired a fertility-preserving treatment. We performed robot-assisted laparoscopic adenomyomectomies. The dysmenorrhea and pelvic pain of the patients nearly disappeared after surgery. No residual adenomyosis was observed on the follow-up pelvic MRI. A robot-assisted laparoscopic adenomyomectomy was feasible, and could be a minimally invasive surgical option for fertility-sparing treatment in patients with adenomyosis.


Lactobacillus acidophilus Endocarditis Complicated by Pauci-Immune Necrotizing Glomerulonephritis.
Infective endocarditis (IE) is more common in patients with predisposing cardiac lesions and has many potential complications, including stroke and arterial thromboembolisms. Renal manifestations have an estimated prevalence of ∼20%. Rapidly progressive glomerulonephritis (RPGN) is a nephrological emergency manifested by autoimmune-mediated progressive loss of renal function over a relatively short period of time. Here, we report the case of a 60-year-old Caucasian male, who presented with speech impairment and was found to have multiple embolic strokes caused by aortic valve IE. His renal function declined rapidly, and his urine sediment featured hematuria and proteinuria. ANCA titer was negative by immunofluorescence (IF); however, the PR3 antibody was elevated. The renal biopsy revealed pauci-immune focally necrotizing glomerulonephritis with the presence of ∼25% cellular crescents. He was initially treated with plasmapheresis and pulse dose steroids. Hemodialysis was initiated for uremic symptoms. After four weeks of antibiotic therapy and with blood cultures remaining negative, he was treated with rituximab. Two months after discharge, his renal function showed improvement, and hemodialysis was discontinued. This case highlights several complications associated with lactobacillus endocarditis including RPGN.


Towards Genotype-Specific Care for Chronic Hepatitis B: The First 6 Years Follow Up From the CHARM Cohort Study.
There is increasing evidence to suggest that, among those with chronic hepatitis B virus infection, the natural history and rate of progression to cirrhosis and hepatocellular carcinoma is influenced by hepatitis B virus genotype. The unique hepatitis B virus genotype C4 circulates among Indigenous Australians. The aim of this work is to describe the process of establishing this cohort and review the first 6 years of available data in an effort to understand the real-world clinical care and natural history of this subgenotype. We followed a longitudinal cohort of Indigenous Australians from the Northern Territory of Australia with established subgenotype C4 infections. We assigned phases of disease according to Gastroenterological Society of Australia and Asian Pacific Association for the Study of the Liver criteria using clinical and laboratory information that had been collected for clinical management. Of 193 patients followed over a median of 38 months, 58 (30%) individuals transitioned from 1 disease phase to another, 10 (5%) cleared hepatitis B e antigen, and 6 cleared hepatitis B surface antigen (3%). In this relatively young cohort (median age 40.3 years), 26 (13%) had cirrhosis by the end of the follow up period, with the majority of these being in the immune control phase of disease. In this cohort of hepatitis B subgenotype C4 patients, we report an aggressive and dynamic clinical phenotype. High rates of cirrhosis at a young age appear to occur in the early phases of disease.


[Clinical effects of different ways of mechanical ventilation combined with pulmonary surfactant in treatment of acute lung injury/acute respiratory distress syndrome in neonates: a comparative analysis].
To compare the therapeutic effects of high-frequency oscillatory ventilation+pulmonary surfactant (HFOV+PS), conventional mechanical ventilation+pulmonary surfactant (CMV+PS), and conventional mechanical ventilation (CMV) alone for acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in neonates. A total of 136 neonates with ALI/ARDS were enrolled, among whom 73 had ALI and 63 had ARDS. They were divided into HFOV+PS group (n=45), CMV+PS group (n=53), and CMV group (n=38). The neonates in the first two groups were given PS at a dose of 70-100 mg/kg. The partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), PaO2/fraction of inspired oxygen (FiO2), oxygenation index (OI), and respiratory index (RI) were measured at 0, 12, 24, 48, and 72 hours of mechanical ventilation. At 12, 24, and 48 hours of mechanical ventilation, the HFOV+PS group had higher PaO2 and lower PaCO2 than the CMV+PS and CMV groups (P<0.05). At 12, 24, 48, and 72 hours of mechanical ventilation, the HFOV+PS group had higher PaO2/FiO2 and lower OI and RI than the CMV+PS and CMV groups (P<0.05). The HFOV+PS group had shorter durations of mechanical ventilation and oxygen use than the CMV+PS and CMV groups (P<0.05). There were no significant differences in the incidence rates of air leakage and intracranial hemorrhage and cure rate between the three groups. In neonates with ALI/ARDS, HFOV combined with PS can improve pulmonary function more effectively and shorten the durations of mechanical ventilation and oxygen use compared with CMV+PS and CMV alone. It does not increase the incidence of complications.


Synthesis, Characterization, and Antifungal Activity of Schiff Bases of Inulin Bearing Pyridine ring.
As a renewable, biocompatible, and biodegradable polysaccharide, inulin has a good solubility in water and some physiological functions. Chemical modification is one of the important methods to improve the bioactivity of inulin. In this paper, based on 6-amino-6-deoxy-3,4-acetyl inulin (3), three kinds of Schiff bases of inulin bearing pyridine rings were successfully designed and synthesized. Detailed structural characterization was carried out using FTIR, 13C NMR, and ¹H NMR spectroscopy, and elemental analysis. Moreover, the antifungal activity of Schiff bases of inulin against three plant pathogenic fungi, including Botrytis cinerea, Fusarium oxysporum f.sp.niveum, and Phomopsis asparagi, were evaluated using in vitro hypha measurements. Inulin, as a natural polysaccharide, did not possess any antifungal activity at the tested concentration against the targeted fungi. Compared with inulin and the intermediate product 6-amino-6-deoxy-3,4-acetyl inulin (3), all the synthesized Schiff bases of inulin derivatives with >54.0% inhibitory index at 2.0 mg/mL exhibited enhanced antifungal activity. 3NS, with an inhibitory index of 77.0% exhibited good antifungal activity against Botrytis cinerea at 2.0 mg/mL. The synthesized Schiff bases of inulin bearing pyridine rings can be prepared for novel antifungal agents to expand the application of inulin.


Comparative analysis of expression profiles of chemokines, chemokine receptors, and components of signaling pathways mediated by chemokines in eight cell types during rat liver regeneration.
It has been documented that chemokines can positively regulate liver regeneration at the tissue level after partial hepatectomy. However, the precise mechanism of the effects of chemokines on regeneration at the cellular level remains poorly defined. In this study, 8 cell types from rat regenerating liver at 8 recovery time points after 2/3 hepatectomy were isolated and purified using Percoll density gradient centrifugation and immunomagnetic bead methods. The expression profiles of each cell type were monitored using a microarray. RT-PCR analysis was performed to validate the reliability of the microarray results. The results showed that, on the whole, the expression profiles of chemokine and receptor genes varied among different cell types; most genes involved in chemokine signaling pathways showed an increase in expression across the 8 liver cell types during liver regeneration. The implication of these genes in regeneration was analyzed by bioinformatics and systems biology methods. According to the microarray results and gene synergy, activation of chemokine signaling pathways at 24 h in biliary epithelial cells and at 2-12 h in dendritic cells may be triggered by CCL2-CCR2 and CCL7-CCR3, respectively; activation of Plc/Pkc and Pi3k/Akt pathways at 2-12 h in sinusoidal endothelial cells might be caused by CCL7-CCR1; and activation of the Src/Ptk, Src/Vav, and Plc/Pkc pathways at the priming stage may be related to the inductive effect of CCL7. These data suggest the potential relevance of the pro-inflammatory chemokines for liver regeneration at the cellular level.


Interleukin-11 attenuates human vascular smooth muscle cell proliferation.
Interleukin (IL)-11 is a growth factor for megakaryocytes, osteoclasts, and intestinal mucosa. IL-11 is also an anti-inflammatory agent, mediating many of its effects by inhibition of the transcriptional activator nuclear factor (NF)-kappa B. The purposes of this study were to examine the effects of IL-11 on human vascular smooth muscle cell (VSMC) proliferation and NF-kappa B activity. VSMC were cultured from human transplant donor aortas, stimulated with basic fibroblastic growth factor (bFGF), and treated with IL-11. VSMC stimulated with bFGF demonstrated an increase in cell number by direct cell counting and mitochondrial activity. IL-11 caused a concentration-dependent decrease in bFGF-induced VSMC proliferation. Furthermore, IL-11 attenuated bFGF-induced increases in cytoplasmic and intranuclear unbound NF-kappa B p65. Similarly, IL-11 attenuated VSMC expression of two NF-kappa B-dependent cytokines, IL-8 and IL-6. Stimulated VSMC did not secrete IL-11, suggesting that endogenous IL-11 did not account for our observations. In conclusion, IL-11 inhibits human VSMC proliferation in vitro and is associated with suppression of NF-kappa B.


Transcellular route of diffusion through stratum corneum: results from finite element models.
Insight into the stratum corneum (SC) permeation pathway for hydrophilic compounds is gained by comparing experimental measurements of permeability and lag time (tlag) with the predictions of a finite element (FE) model. A database of permeability and lag time measurements (n=27) of hydrophilic compounds was compiled from the literature. Transcellular and lateral lipid diffusion pathways were modeled within a brick-and-mortar geometry representing fully hydrated human SC. Modeled tlag's for the lipid pathway are too brief to account for the experimental quantities, whereas the transcellular pathway with preferential corneocyte partitioning does account for them. Measured tlag's are highly correlated (p<0.0001) with the compound's octanol-water partition coefficient, supporting the hypothesis of an aqueous-lipid partition mechanism in the permeation of hydrophilic compounds. The importance of the lag time for identifying the diffusion pathway is demonstrated.


Catecholamine and beta-adrenoceptor influences on airway reactivity to antigen in guinea pigs.
The aim of the present study was to analyze the increased airway reactivity to antigen induced by beta-adrenoceptor blockade, adrenalectomy or medullectomy and to assess the contribution of circulating catecholamines to the increased reactivity. In anesthetized guinea pigs sensitized to ovalbumin (OA), administration of OA produced a dose-related bronchoconstriction characterized by threshold increases in airway insufflation pressure at 0.1 mg/kg i.v. and a near-maximal increase by 0.3 mg/kg i.v. Pretreatment with R(+) propranolol (0.5 mg/kg i.v.) 5 min prior to antigen did not significantly alter airway responses to antigen when compared to vehicle-treated animals. However, pretreatment with 0.5 mg/kg i.v. S(-) propranolol, racemic propranolol or nadolol markedly enhanced (10- to 15-fold) the airway response to the low-dose antigen. In addition, in guinea pigs which had been adrenalectomized, the reactivity to low-dose antigen was enhanced to a similar extent as that of beta-antagonist-treated animals when compared to sham-operated animals. Baseline plasma concentrations of epinephrine were significantly higher in sham-operate guinea pigs (1,494 +/- 223 ng/ml) when compared to adrenalectomized animals (412 +/- 44 ng/ml). Upon antigen exposure, epinephrine levels rose 5-fold (6,859 +/- 1,308 ng/ml) from baseline in sham-operated guinea pigs and were not significantly changed in adrenalectomized animals (848 +/- 208 ng/ml). Specific airway conductance measurements in conscious guinea pigs revealed that animals which had been medullectomized 2 weeks previously responded to lower provocative concentrations of aerosol OA (0.05-0.5%) than corresponding sham-operated animals. Airway reactivity to inhaled acetylcholine (0.1-1%) was similar in medullectomized and sham guinea pigs. Plasma concentrations of epinephrine were significantly lower in medullectomized guinea pigs (327 +/- 88 ng/ml) when compared to sham-operated animals (832 +/- 162 ng/ml). The results of the present study indicate that beta-adrenoceptor antagonism or changes in circulating epinephrine levels markedly alter the response to antigen in sensitized guinea pigs.


Diagnosis and management of GI stromal tumors by EUS-FNA: a survey of opinions and practices of endosonographers.
There is no consensus regarding the best management strategy for diagnosing and treating GI stromal tumors (GISTs). Our purpose was to examine the practice patterns of endosonographers in diagnosing and managing GISTs, particularly features of GISTs suggestive of malignancy, features that prompt surgical referral, and surveillance patterns. An invitation to complete an online survey was e-mailed to all 413 members of the American Society for Gastrointestinal Endoscopy EUS Special Interest Group. A total of 134 (32%) members responded; 59% of respondents use EUS features combined with FNA findings to diagnose GIST, and 89% consider a c-kit-positive stain on FNA most suggestive of GIST. However, 60% would diagnose GIST when cytologic samples are insufficient for diagnosis, and 40% would diagnose GIST if cytologic samples are sufficient but c-kit is negative. A total of 92% use size as the main criterion to distinguish benign from malignant GISTs, and 90% refer lesions >5 cm for surgery. For lesions not resected, 70% survey annually, 19% less than annually, 10% more than annually, and 1% do not survey. The opinions of the respondents do not necessarily reflect the opinions and practices of endosonographers nationwide. There are inherent limitations to an online multiple-choice survey, including low response rates. There are substantial practice variations in diagnosing, resecting, and surveying GISTs. A majority of our survey respondents have made the diagnosis of GIST without FNA confirmation. Size >5 cm is the feature used most to predict malignancy and to prompt surgical referral. Surveillance practices for unresected GISTs are variable. Evidence is needed to establish practice guidelines in this area.


An Iron-Porphyrin Complex with Large Easy-Axis Magnetic Anisotropy on Metal Substrate.
Easy-axis magnetic anisotropy separates two magnetic states with opposite magnetic moments, and single magnetic atoms and molecules with large easy-axis magnetic anisotropy are highly desired for future applications in high-density data storage and quantum computation. By tuning the metalation reaction between tetra-pyridyl-porphyrin molecules and Fe atoms, we have stabilized the so-called initial complex, an intermediate state of the reaction, on Au(111) substrate, and investigated the magnetic property of this complex at a single-molecule level by low-temperature scanning tunneling microscopy and spectroscopy. As revealed by inelastic electron tunneling spectroscopy in magnetic field, this Fe-porphyrin complex has magnetic anisotropy energy of more than 15 meV with its easy-axis perpendicular to the molecular plane. Two magnetic states with opposite spin directions are discriminated by the dependence of spin-flip excitation energy on magnetic field and are found to have long spin lifetimes. Our density functional theory calculations reveal that the Fe atom in this complex, decoupled from Au substrate by a weak ligand field with elongated Fe-N bonds, has a high-spin state S = 2 and a large orbital angular momentum L = 2, which give rise to easy-axis anisotropy perpendicular to the molecular plane and large magnetic anisotropy energy by spin-orbit coupling. Since the Fe atom is protected by the molecular ligand, the complex can be processed at room or even higher temperatures. The reported system may have potential applications in nonvolatile data storage, and our work demonstrates on-surface metalation reactions can be utilized to synthesize organometallic complexes with large magnetic anisotropy.


The chemistry of vitamin B 12. The co-ordination of biologically important molecules.
The following equilibrium constants (given as logK in units of m(-1)) were determined for the substitution of co-ordinated H(2)O in aquocobalamin by glycine (bound through N) 5.8, cysteine (bound through S) 6.0 or 8.3, depending on the value chosen for the pK of the thiol group, and phenolate 2.9. The spectrum of the phenolate cobalamin shows an additional intense absorption band at 468nm with a molar extinction coefficient of 1.1x10(4), which is assigned to a charge transfer from the phenolate to the cobalt ion. Equilibrium constants have also been determined for the equilibria between adenylcobamide cyanide and CN(-), HO(-) and H(+), which show that the adenine is more easily displaced by CN(-) and HO(-) than is 5,6-dimethylbenziminazole in vitamin B(12), but can be protonated by acid while still remaining co-ordinated to the cobalt. It is shown that in the binding of corrinoids to proteins and polypeptides the formation of hydrogen bonds is far more important than co-ordination by the metal.


Translating Hedgehog in Cancer: Controlling Protein Synthesis.
Developmental Hedgehog (Hh) signaling is found deregulated in a broad spectrum of human malignancies and, thus, is an attractive target for cancer therapy. Currently available Hh inhibitors have shown the rapid occurrence of drug resistance, due to altered signaling in collateral pathways. Emerging observations suggest that Hh signaling regulates protein translation in pathways that depend both on Cap- and IRES-mediated translation. In addition, translational regulators have been shown to modulate Hh function. In this opinion, we describe this novel Hh/translation crosstalk and argue that it plays a relevant role in Hh-mediated tumorigenesis and drug resistance. As such, we suggest that drugs targeting translation might be introduced in novel protocols aimed at treating malignancies driven by aberrant Hh signaling.


Psychological treatment of emotional problems by general practitioners.
Since the pioneering work of Balint (1964; Balint & Norell, 1973) there has been little empirical study of general medical practitioners' psychological treatment of patients presenting with emotional problems. In this study 88 patients presenting to GPs for help with emotional problems were interviewed at home about their experiences of their consultations with the GPs. Their audiotaped consultations were then analysed using four different coding systems: a content coding system devised for the study, two verbal response mode systems (Byrne & Long, 1976; Stiles, 1982), and ratings of the doctor's empathic understanding and concern and warmth. Less than half the average consultation was found to comprise psychological treatment broadly defined as any discussion and listening to patients' psychosocial concerns. Although psychological treatment generally was associated with positive patient experiences, the strongest effects found were for listening interactions (where patients described their problems in their own words with non-directive encouragement from the doctor) and for rated doctor empathy. The results are discussed in relation to the work of Balint (1964) and associated findings in empirical studies of psychotherapy.


Assessment of the aggregation state of integral membrane proteins in reconstituted phospholipid vesicles using small angle neutron scattering.
The assessment of the physical size of integral membrane protein complexes has generally been limited to samples solubilized in non-ionic detergent, a process which may introduce artifacts of unknown scope and severity. A system has been developed that allows observation of the small angle scattering profile of an integral membrane protein while incorporated in small unilamellar phospholipid vesicles. Contrast matching of isotopically substituted phospholipid eliminates the contribution of the bilayer to the observed scattering, resulting in a profile dependent only on the structure of the individual membrane protein complexes and their spatial arrangement in the vesicle. After appropriate compensation for their spatial arrangement, information about the molecular mass and radius of gyration of the individual complexes can be obtained. The validity of the approach has been established using monomeric bacteriorhodopsin as a model system.


Descriptive epidemiology of changes in objectively measured sedentary behaviour and physical activity: six-year follow-up of the EPIC-Norfolk cohort.
Sedentary time increases and total physical activity decreases with age. The magnitude and correlates of changes in sedentary time, light-intensity physical activity (LPA), moderate-to-vigorous intensity physical activity (MVPA), and overall physical activity remain unclear. We quantified these changes and identified their individual and sociodemographic correlates. We used data from 1259 adults (67.8 ± 6.9 years; 41.9% women) who participated in the EPIC-Norfolk Study. Activity was assessed at baseline (2004-2011) and follow-up (2012-2016) for 7 days using accelerometers. Potential correlates of change were specified a priori. We used unadjusted and adjusted sex-stratified linear regressions to identify correlates of change. Only 3.7% of adults met the current MVPA recommendations. Sedentary time increased by 3.0 min/day/year (SD = 12.3). LPA, MVPA, and overall PA decreased by 1.7 min/day/year (SD = 5.4), 3.0 min/day/year (SD = 6.0), and 8.8 cpm/year (SD = 18.8), respectively. Correlates of greater rates of increase in sedentary time included older age and higher BMI in men, and older age, higher BMI, smoking, and urban dwelling in women. Correlates of greater rates of decrease in physical activity included older age, higher BMI, living alone, depression, car use, and/or fair/poor self-rated health in men, and older age, higher BMI, depression, smoking, and/or urban dwelling in women (e.g. depressed women had a 1.0 min/day/year greater rate of decline in MVPA than non-depressed women, 95% CI -1.8, - 0.2). Most (> 95%) adults are insufficiently active. Sedentary time increases and LPA, MVPA and overall physical activity decreases over time, with more pronounced rates of change observed in specific sub-groups (e.g. among older and depressed adults). To promote active living, the correlates of these changes should be considered in future interventions.


Computers in nursing research.
Nicola Eaton launches a four-part, monthly series by considering the range of uses of computer hardware and software for nurse researchers. The other articles in the series will look at expert systems in nursing, computers in nurse education and interactive video as a teaching medium.


Extraparenchymal neurocysticercosis in the United States.
Neurocysticercosis (NCC) is endemic in the developing world but is becoming more common in the United States because of immigration. Although NCC is pleomorphic in its presentation, extraparenchymal NCC may be challenging to diagnose and treat. Extraparenchymal NCC is probably more frequent than previously thought. Neurologists and neuroradiologists in the United States are often unaware of the pretreatment/post-treatment radiographic patterns of extraparenchymal NCC and the potentially poor prognosis if not correctly diagnosed and managed. The review of this condition is important given increasing incidence in the United States.


Expression of MRP and mdr1 in human gastrointestinal cancer cell lines: a correlation with resistance against doxorubicin.
The mRNA expression of mdr1 and MRP, each of which codes for a transport protein belonging to ATP-binding cassette superfamily and are reported to be responsible for multidrug resistance phenotype, were semi-quantified by RT-PCR in a panel of gastrointestinal cancer cell lines. Although the expression of MRP was predominant in esophageal cancer cell lines, expression of either or both of the genes was detected in all the cell lines tested. Expression of these two genes added together correlated significantly with chemosensitivity against doxorubicin, implicating that expression of both genes should be evaluated in the future analysis of multidrug resistance phenotype. The ID50 values for pirarubicin, although generally lower than the values for doxorubicin, correlated well with the latter, suggesting that the similar phenotype as that for doxorubicin might be responsible for drug resistance against this semisynthetic anthracycline glycoside.


Phoneme manipulation not onset-rime manipulation ability is a unique predictor of early reading.
Phonological awareness is known to be an excellent predictor of later reading acquisition. It remains unclear, however, whether phoneme manipulation alone best explains this association or whether an additional direct contribution of onset-rime awareness is predictive. This issue is explored here. A longitudinal study is reported predicting national test and teacher-assessed performance of 351 children aged 7 from phonological awareness measures, pupil baseline attainment and background measures at age 5. Explicit phoneme manipulation skills at age 5 correlated most strongly with literacy skills at age 5. Phoneme manipulation at age 5 predicted all four reading measures taken at age 7 after pupil background, baseline data and onset-rime awareness were controlled in regression analyses. Onset-rime manipulation did not predict reading at 7 in parallel analyses. After controlling for initial reading at age 5, phoneme manipulation still predicted reading comprehension, and teacher-assessed reading and writing at age 7. Results support the existence of a route from phoneme manipulation, but not an additional direct route from explicit onset-rime manipulation at 5, to reading at 7. Practically, findings show that professionals can augment baseline and pupil background data with phoneme manipulation screening in the early identification of learning needs.


Role of cyclic GMP and calcineurin in homologous and heterologous desensitization of natriuretic peptide receptor-A.
The natriuretic peptide receptor-A (NPR-A) mediates natriuretic, hypotensive, and antihypertrophic effects of natriuretic peptides through the production of cGMP. In pathological conditions such as heart failure, these effects are attenuated by homologous and heterologous desensitization mechanisms resulting in the dephosphorylation of the cytosolic portion of the receptor. In contrast with natriuretic peptide-induced desensitization, pressor hormone-induced desensitization is dependent on protein kinase C (PKC) stimulation and (or) cytosolic calcium elevation. Mechanisms by which PKC and Ca(2+) promote NPR-A desensitization are not known. The role of cGMP and of the cytosolic Ca(2+) pathways in NPR-A desensitization were therefore studied. In contrast with the activation of NPR-A by its agonist, activation of soluble guanylyl cyclases of LLC-PK1 cells by sodium nitroprusside also leads to a production of cGMP but without altering NPR-A activation. Consequently, cGMP elevation per se does not appear to mediate homologous desensitization of NPR-A. In addition, cytosolic calcium increase is required only for the heterologous desensitization pathway since the calcium chelator BAPTA-AM blocks only PMA or ionomycin-induced desensitization. Calcineurin inhibitors block the NPR-A guanylyl cyclase heterologous desensitization induced by ionomycin, suggesting an essential role for this Ca(2+)-stimulated phosphatase in NPR-A desensitization. In summary, the present report demonstrates that neither cGMP nor Ca(2+) cytosolic elevation cause NPR-A homologous desensitization. Our results also indicate for the first time a role for calcineurin in NPR-A heterologous desensitization.


Three-dimensional motion detection of a 20-nm gold nanoparticle using twilight-field digital holography with coherence regulation.
In the twilight-field method for obtaining interference fringes with high contrast in in-line digital holography, only the intensity of the reference light is regulated to be close to the intensity of the object light, which is the ultra-weak scattered light from a nanoparticle, by using a low-frequency attenuation filter. Coherence of the light also strongly affects the contrast of the interference fringes. High coherence causes a lot of undesired coherent noise, which masks the fringes derived from the nanoparticles. Too-low coherence results in fringes with low contrast and a correspondingly low signal-to-noise ratio. Consequently, proper regulation of the coherence of the light source, in this study the spectral width, improves the minimum detectable size in holographic three-dimensional position measurement of nanoparticles. By using these methods, we were able to measure the position of a gold nanoparticle with a minimum diameter of 20 nm.


Positively deviant networks: what are they and why do we need them?
This paper aims to report "positively deviant" experiences of three public sector networks seeking to enhance organizational and system level capacities. It is the authors' thesis that the knowledge base concerning the true benefits and pitfalls of networks can be captured and interpreted only through intense, ongoing learning effort embedded in practice on the ground, combined with sustained in-depth observation and collaborative research. The paper describes through case examples why and how different kinds of networks within different jurisdictional contexts and different organizational cultures are being used to enhance the climate for change towards better health care and improved health. The authors describe the contexts, structures, processes and impacts of three "positively deviant" networks. The network form can provide opportunity for nurturing changes and innovations within large organizational and complex system environments. This opportunity to create additional and different pathways for improved decision making and service provision comes with challenges that should be recognized. The authors' experiences indicate that, for networks, a key component of success relates to pulling and pushing at the edges of multiple connections and boundaries in "positively deviant" ways. This pushing and pulling is intrinsically evidence of organizational and intraorganizational learning--in the examples presented--for the improvement of health care and health. Other networks can learn from the reported experiences and add their own cases to the empirical understanding of how networks can make a difference; this in turn can help the conceptual and theoretical understanding of them.


Comparison of echocardiographic indices of right ventricular systolic function and ejection fraction obtained with continuous thermodilution in critically ill patients.
Though echocardiographic evaluation assesses the right ventricular systolic function, which of the existing parameters best reflects the right ventricular ejection fraction (RVEF) in the critically ill patients is still uncertain. We aimed to determine the relationship between echocardiographic indices of right ventricular systolic function and RVEF. Prospective observational study was conducted in a mixed Surgical Intensive Care Unit (Hôpital Lariboisière, Paris, France) from November 2017 to November 2018. All critically ill patients monitored with a pulmonary artery catheter were assessed. We collected echocardiographic indices of right ventricular function (tricuspid annular plane systolic excursion, TAPSE; peak systolic velocity of pulsed tissue Doppler at lateral tricuspid annulus, S'; fractional area change, FAC; right ventricular index of myocardial performance, RIMP; isovolumic acceleration, IVA; end-diastolic diameter ratio, EDDr) and compared them with the RVEF obtained from continuous volumetric pulmonary artery catheter. Twenty-five patients were analyzed. Admission diagnosis was acute heart failure in 11 patients and septic shock in 14 patients. Median age was 70 years [57-80], norepinephrine median dose was 0.29 μg/kg/min [0.14-0.50], median Sequential Organ Failure Assessment score was 12 [10-14], and mortality at day 28 was 56%. When compared to RVEF, TAPSE had the highest correlation coefficient (rho = 0.78, 95% CI 0.52 to 0.89, p < 0.001). S' was also correlated to RVEF (rho = 0.64, 95% CI 0.60 to 0.80, p = 0.001) whereas FAC, RIMP, IVA, and EDDr did not. TAPSE lower than 16 mm, S' lower than 11 cm/s, and EDDr higher than 1 were always associated with a reduced RVEF. We found that amongst indices of right ventricular systolic function, TAPSE and S' were well correlated with thermodilution-derived RVEF in critically ill patients.


Odd carbon long linear chains HC2n+1H (n = 4-11): properties of the neutrals and radical anions.
The optimized geometries, adiabatic electron affinities, vertical electron affinities, vertical electron detachment energies (for the anions), and IR-active vibrational frequencies have been predicted for the long linear carbon chains HC(2)(n)()(+1)H (n = 4-11). The B3LYP density functional combined with DZP and TZ2P basis sets was used in this theoretical study. These methods have been extensively calibrated versus experiment for the prediction of electron affinities (Chem. Rev. 2002, 102, 231). The computed physical properties are discussed and compared with the even carbon chains HC(2)(n)()H. The predicted electron affinities form a remarkably regular sequence: 2.12 eV (HC(9)H), 2.42 eV (HC(11)H), 2.66 eV (HC(13)H), 2.85 eV (HC(15)H), 3.01 eV (HC(17)H), 3.14 eV (HC(19)H), 3.25 eV (HC(21)H), and 3.35 eV (HC(23)H). These electron affinities are as much as 0.4 eV higher than those for analogous even carbon chains. The predicted structures display an intermediate cumulene-polyacetylene type of bonding, with the inner carbons appearing cumulenic and the outer carbons polyacetylenic.


Secondary hemophagocytic syndrome in adults: a case series of 18 patients in a single institution and a review of literature.
Hemophagocytic lymphohistiocytosis (HLH) is rare in adults and is usually fatal without treatment. We present a consecutive series of 18 adults with HLH diagnosed at our institution between 2004 and 2009. All diagnoses were confirmed by pathology. The median age at diagnosis was 56 years (range: 18-73 years), with a male: female ratio of 2:1. Patients uniformly presented with fever. Fifty-five per cent of the patients presented with evidence of hepatomegaly or splenomegaly. All of the patients had at least a bi- or trilineage cytopenia. Elevated liver enzymes, hyperferritinemia, hypertriglyceridemia and hyperfibrinogenemia were seen in 50, 100, 40 and 50% of patients, respectively. The presumed causes were as follows; haematological malignancies (n = 4), post-autologous stem cell transplant (n = 2), infection (n = 2), rheumatologic illness (n = 2), sickle cell disease (n = 1), post-orthotopic liver transplant (n = 1) and idiopathic (n = 3). The median time from suspicion to diagnosis was 5 days (1-27 days). Corticosteroids and/or cyclosporine were the most frequently used treatment regimen. Other agents used were etoposide, IVIG, cyclophosphamide and chemotherapy. The mortality rate was 72%, with multi-system organ failure being the most common cause of death. Median survival time from diagnosis was 35 days. Six patients are alive to date. In a univariate analysis, the presence of fever was the only factor that was statistically significant for predicting a poor prognosis (early mortality) (p = 0.05). In conclusion, a high index of suspicion is the critical factor for early diagnosis. Early treatment with immunosuppressant is warranted, and a thorough diagnostic evaluation to identify the underlying cause should be undertaken.


Investigating Genetic and Other Determinants of First-Onset Myocardial Infarction in Malaysia: Protocol for the Malaysian Acute Vascular Events Risk Study.
Although the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse. The Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results. By June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire. Tobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; P<.001), previous smoking (OR 1.34, 95% CI 1.12-1.60; P=.001), a history of high blood pressure (OR 2.13, 95% CI 1.86-2.44; P<.001), a history of diabetes mellitus (OR 2.72, 95% CI 2.34-3.17; P<.001), a family history of coronary heart disease (OR 1.28, 95% CI 1.07-1.55; P=.009), and obesity (BMI >30 kg/m2; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models. The MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action. RR1-10.2196/31885.


[Intraperitoneal hemorrhage during and after percutaneous radiofrequency ablation of hepatic tumors: reasons and management].
Intraperitoneal hemorrhage is one of the most common complications of radiofrequency (RF) ablation of hepatic tumors. This study was designed to investigate the reason and management of intraperitoneal hemorrhage occurred during or after percutaneous RF ablation of hepatic tumors. Three hundred and fifty-six patients with hepatic tumors have been treated at 592 procedures of ultrasound guided RF ablation. Intraperitoneal hemorrhage occurred in 5 patients (0.8%). The reasons and management of intraperitoneal hemorrhage in these 5 cases were retrospectively analyzed. Two patients with liver metastasis and one hepatocellular carcinoma (HCC) patient suffered from hemorrhage during the RF treatment. Two patients with recurrent HCC after surgery developed hemorrhage 20 minutes or 4 hours after RF treatment. One case of hemorrhage was due to the inappropriate electrode positioning induced liver laceration while treating a 1 cm liver metastasis near the liver capsule. One was due to the injury of a small vessel by the RF needle in another liver metastasis patient. Three cases were due to tumor rupture with two cases induced by cough or position change after treating large protruding HCC lesions. Four (80%) of the 5 cases of hemorrhage were rapidly identified by ultrasound. The causes and sites of bleeding during the RF treatment in three cases were confirmed through ultrasound, which were successfully treated using RF coagulation to achieve hemostasis of the bleeding site. Two patients with post-ablation hemorrhage recovered in one hour and 24 hours, respectively after given blood transfusion and other conservative measures. No surgical intervention was required. Two patients died of wide spread metastasis 23 - 36 months afterwards and the other three patients have lived for 18 - 25 months to date. It is important to perform close monitoring during and after RF ablation in order to identify intraperitoneal hemorrhage in time. RF ablation of the bleeding sites was a simple and effective management when the bleeding site could be confirmed by ultrasound. The hemorrhage due to the rupture of large and protruding liver tumors could be serious and should be considered as contraindication for RF treatment.


Live attenuated influenza virus (LAIV) induces different mucosal T cell function in nonsmokers and smokers.
Smokers are more susceptible to respiratory infections, including influenza. To explore the effect of smoking on influenza-induced responses within the nasal mucosa, we have developed a protocol using inoculation with live attenuated influenza virus (LAIV) vaccine followed by sampling of the nasal mucosa. Mucosal cell populations were harvested through superficial biopsy of the nasal inferior turbinate pre and post LAIV inoculation and analyzed using flow cytometry. The majority of nasal biopsy CD45+ immune cells at baseline were CD3+ T lymphocytes. Following LAIV, these lymphocytes increased in nonsmokers but not in smokers. A subset of individuals was negative for helper T cell marker CD4 and cytotoxic T cell marker CD8 but positive for the γδ T cell receptor (TCR). Increases in γδ TCR+ cells were greater in nonsmokers, than in smokers. Thus, LAIV-induced changes in CD3 T as well as γδ T lymphocyte percentages are suppressed in smokers compared to nonsmokers.


[Unmarried, pre-nuptial and marital fertility: the family in process of change. An empirical analysis of Austrian women giving birth to their first child, 1950-1990].
"This analysis provides an outline of the changes in family formation behaviour in Austria in the years 1950 to 1990. Using vital statistical data and retrospective data of the 1981 census all women with their first confinement in the years 1950 to 1990 were classified into three distinct groups according to their form of family formation behaviour: 1. Mother is unmarried at date of birth...,2. mother marries during pregnancy, 3. mother is married at time of conception. Changes in family formation behaviour over time are discussed in detail, focussing on different age groups and on regional differences." (SUMMARY IN ENG)


A novel system for the comprehensive collection of nonvolatile molecules from human exhaled breath.
Characterization of nonvolatile molecules in exhaled breath particles can be used for respiratory disease monitoring and diagnosis. Conventional methods for the collection of nonvolatile molecules in breath heavily rely on the physical properties of exhaled breath particles. Strategies taking advantage of their chemical properties have not yet been explored. In the present study, we developed a column system in which the surface chemistry between organic nonvolatile molecules and octadecyl carbon chain was exploited for the comprehensive collection of metabolites, lipids, and proteins. We demonstrated that the collection system had the capture efficiency of 99% and the capacity to capture representative nonvolatile molecules. The collection system was further evaluated using human subjects and proteins collected from human exhaled breath were characterized and identified using gel electrophoresis and bottom-up proteomics. The identified 303 proteins from mass spectrometry were further searched against reported bronchoalveolar lavage fluid proteomes and it was shown that 60 proteins have the tissue origin of lower respiratory airways. In summary, we demonstrate that our collection system can collect nonvolatile molecules from human exhaled breath in an efficient and comprehensive manner and has the potential to be used for the study of respiratory diseases.


Enhanced protoplast growth at the interface between oxygenated fluorocarbon liquid and aqueous culture medium supplemented with pluronic F-68.
Protoplasts isolated from cell suspensions of albino Petunia hybrida were grown for 10 d at the interface between aqueous culture medium and oxygenated perfluorodecalin. Protoplasts synthesised new cell walls and divided normally at the fluorocarbon/culture medium interface, the mean division frequency of protoplasts being increased by 37% (P < 0.05) in this system when the perfluorodecalin was saturated with oxygen prior to use. The mean division frequency of protoplasts was further increased to a maximum of 52% above control (P < 0.01) when the medium overlaying the oxygenated perfluorodecalin was supplemented with 0.01% (w/v) of the co-polymer surfactant, Pluronic F-68. These results demonstrate a beneficial and synergistic effect of supplementing protoplast culture systems with oxygenated perfluorodecalin and Pluronic F-68.


Comparison of intraocular treatment of DMTU and SOD following retinal ischemia in rats.
The effect of intravitreal injections of DMTU (dimethylthiourea) and SOD (superoxide dismutase), two free radical scavengers, was evaluated in a rat model of retinal ischemia induced by elevated intraocular pressure. The drugs were administered just before or just after a 60 min ischemia. At days 2 and 7 after reperfusion, retinal recovery was evaluated by electroretinography. At day 7, layer thicknesses and cell rows were measured from histologic sections of paraffin-embedded retinas. In the vehicle-treated control group, we observed a decrease in the inner retinal layers and b-wave amplitude impairment. SOD injection (6 units/eye) protected the retina from ischemia/reperfusion injury. At day 2 after reperfusion, electroretinographic recovery was more efficient when SOD was administered just after ischemia (99%) than after pretreatment with SOD (81%) (p<0.03). In the DMTU-treated group (75 microg/eye), only the pretreatment induced significant electrophysiologic (40%) (p<0.001) and morphologic recovery.


Cartilage warping: an experimental model.
Cadaveric cartilage was cut into blocks with a newly devised cartilage cutter. Over one-hundred pieces of cartilage were used to define a kinetics curve of cartilage warping. Kinetics curves were developed for a control group of cartilage blocks placed in saline-soaked gauze (n = 46). In addition, kinetics curves were developed for cartilage placed in hypotonic saline (n = 14), hypertonic saline (n = 14), and cyanoacrylate glue (n = 6). Photographs of all groups were taken at timed intervals in order to plot the cartilage warping. It was found that pieces of cartilage which were cut peripherally (n = 6) warped twice as much as those cut centrally (n = 40). This was significant to p = 0.001. Within 15 minutes, centrally cut pieces of cartilage warped to approximately 90 percent of their end warpage; on the other hand, peripherally cut pieces of cartilage required 30 minutes to warp 90 percent of their destined warpage. The variables used did not significantly alter the kinetics curves as compared with control.


Transgender college students' mental health: Comparing transgender students to their cisgender peers.
Objective: Although researchers in higher education have focused more attention on transgender individuals, gaps remain, particularly related to aspects of health and wellness. Participants: Participants were a nationally representative sample of college students. Methods:Anova and follow up post hoc tests were utilized to examine measures of transgender college students' mental health in comparison to their cisgender peers who identify as heterosexual, lesbian, gay, and bisexual. Results: Findings indicate that transgender students were more likely to report physically harming themselves or attempt suicide, but responded similarly to peers on other measures. Conclusions: Individuals who work with transgender college students can benefit from this reserach by understanding how to support and avoid marginalizing these students.


[Laser-assisted induction of arthrosis].
In a controlled experimental trial the induction of gonarthrosis following laser-assisted meniscectomy was assessed. A XeCl excimer laser (lambda = 308 nm, pulsewidth 20 ns, repetition rate 10-70 Hz, radiant exposure 10-40 mJ/mm2) and a continuous wave Nd:YAG laser (lambda = 1064 nm, energy density 21-93 W/mm2) were employed in connection with 600-micrometer and 800-micrometer quartz fibers, respectively. In an animal model, effects on the remaining meniscus and the corresponding cartilage surfaces were studied in vivo within an observation period of 6 months. For evaluation of the pathogenesis in laser induced arthrosis, morphological and biomechanical studies were performed on native human menisci. Compared to conventional meniscectomy, laser energy effectively prevents further fibrillation of the meniscal structure. A remodelling of the meniscus did not occur in any experimental group. The degree of reactive synovitis, assessed by macroscopic and histologic scoring, was significantly greater following Nd:YAG laser surgery than after excimer laser resection and conventional surgery (P < 0.05). On X-ray, more progression of degenerative changes was observed following laser procedures than after conventional meniscectomy. The proteoglycan content in the femoral cartilage corresponding to the zone of meniscus resection was significantly lower in the laser group than after conventional meniscectomy (P < 0.01), which substantiates macroscopic and radiographic findings indicating degenerative derangement of the hyaline cartilage. On light microscopy and scanning electron microscopy of meniscus specimens, excimer laser irradiation led to well-delineated resection borders with a mean transitional zone of 20 micrometers, whereas menisci exposed to Nd:YAG laser irradiation presented extensive vaporization zones with the surface covered by an amorphous structure. Menisci irradiated by excimer or Nd:YAG laser energy showed significantly increased rigidity (P < 0.05 and P < 0.01); the maximum value of radial strain at flexion was lower following Nd:YAG laser irradiation (mean 1.5 +/- 0.3%) and following excimer laser irradiation (mean 2.4 +/- 0.3%) than in non-irradiated menisci (mean 3.0 +/- 0.5%). These observations lead to the conclusion that laser-assisted meniscectomy promotes the early manifestation of gonarthrosis by virtue of a reduced femorotibial contact area and alterations in the biomechanical properties of the meniscus.


Early embryonic lethality caused by targeted disruption of the mouse thioredoxin gene.
Thioredoxins belong to a widely distributed group of small proteins with strong reducing activities mediated by a consensus redox-active dithiol (Cys-Gly-Pro-Cys). Thioredoxin was first isolated as a hydrogen donor for enzymatic synthesis of deoxyribonucleotides by ribonucleotide reductase in Escherichia coli. Recent studies have revealed a variety of roles that thioredoxin plays in transcription, growth control, and immune function. In this report, we describe the phenotype of mice carrying a targeted disruption of the thioredoxin gene (Txn). Heterozygotes are viable, fertile, and appear normal. In contrast, homozygous mutants die shortly after implantation, and the concepti were resorbed prior to gastrulation. When preimplantation embryos were placed in culture, the inner cell mass cells of the homozygous embryos failed to proliferate. These results indicate that Txn expression is essential for early differentiation and morphogenesis of the mouse embryo.


Ets-related protein PU.1 regulates expression of the immunoglobulin J-chain gene through a novel Ets-binding element.
In a primary immune response, a signal from interleukin-2 (IL-2) activates transcription of the gene encoding the pentamer IgM joining component, the J chain. Recently, a bifunctional control element (JB) in the J-chain promoter has been identified. This finding was pursued in the present study by purifying and characterizing the nuclear protein (NF-JB) that mediates the positive regulatory activity of the JB element. The analyses revealed that NF-JB is identical to the Ets-related B-cell- and macrophage-specific transcriptional factor, PU.1, despite the fact that the JB site lacks the GGA core reported to be essential for binding by members of the Ets oncoprotein family. The two factors were found to be indistinguishable with respect to their DNA-binding characteristics, size, and peptide structure. Moreover, in transient transfection assays, PU.1 alone activated reporter constructs containing the JB cis-element, and the activation was shown to be dependent on a glutamine-rich sequence in the amino-terminal portion of PU.1. Finally, a dominant negative mutant of PU.1 was capable of suppressing the transcriptional activity of a 1.2-kb J-chain promoter sequence. These results establish an important role for PU.1 in the regulation of immunoglobulin J-chain gene expression and provide new insights into the function(s) of the Ets transcription factors in lymphoid cells.


The Sensory and Motor Components of the Cortical Hierarchy Are Coupled to the Rhythm of the Stomach during Rest.
Bodily rhythms appear as novel scaffolding mechanisms orchestrating the spatiotemporal organization of spontaneous brain activity. Here, we follow-up on the discovery of the gastric resting-state network (Rebollo et al., 2018), composed of brain regions in which the fMRI signal is phase-synchronized to the slow (0.05 Hz) electrical rhythm of the stomach. Using a larger sample size (n = 63 human participants, both genders), we further characterize the anatomy and effect sizes of gastric-brain coupling across resting-state networks, a fine grained cortical parcellation, as well as along the main gradients of cortical organization. Most (67%) of the gastric network is included in the somato-motor-auditory (38%) and visual (29%) resting state networks (RSNs). Gastric brain coupling also occurs in the granular insula and, to a lesser extent, in the piriform cortex. Thus, all sensory and motor cortices corresponding to both exteroceptive and interoceptive modalities are coupled to the gastric rhythm during rest. Conversely, little gastric-brain coupling occurs in cognitive networks and transmodal regions. These results suggest not only that gastric rhythm and sensory-motor processes are likely to interact, but also that gastric-brain coupling might be a mechanism of sensory and motor integration that mostly bypasses cognition, complementing the classical hierarchical organization of the human brain.SIGNIFICANCE STATEMENT While there is growing interest for brain-body communication in general and brain-viscera communication in particular, little is known about how the brain interacts with the gastric rhythm, the slow electrical rhythm continuously produced in the stomach. Here, we show in human participants at rest that the gastric network, composed of brain regions synchronized with delays to the gastric rhythm, includes all motor and sensory (vision, audition, touch and interoception, olfaction) regions, but only few of the transmodal regions associated with higher-level cognition. Such results prompt for a reconsideration of the classical view of cortical organization, where the different sensory modalities are considered as relatively independent modules.


Endstage liver disease associated with nitrofurantoin requiring liver transplantation.
To report the apparent development of endstage liver disease secondary to nitrofurantoin administration. A 40-year-old woman developed hepatic failure after receiving nitrofurantoin 200 mg po bid for one month for prophylaxis against urinary-tract infections. Symptoms first occurred after two weeks of nitrofurantoin therapy. Other causes of hepatic failure (e.g., viral infection, autoimmune disorder, concomitant medications, cancer, Wilson's disease, ethanol abuse, pregnancy) were ruled out. Acute and chronic hepatic injury has previously been reported with the use of nitrofurantoin. The proposed mechanism may be immunoallergic or metabolic in origin. On evaluating concomitant diseases and medications in our patient as well as the temporal sequence of her signs and symptoms, it appears that she developed hepatic failure secondary to the use of nitrofurantoin, ultimately necessitating orthotopic liver transplantation. The potential for the development of such a severe adverse reaction warrants careful evaluation of symptoms that may potentially be caused by hepatic damage as well as immediate discontinuation of nitrofurantoin in patients presenting with jaundice.


Navigation Options for Spinal Surgeons: State of the Art 2021.
The use of navigation in spinal surgery has been increasing over the past decade. There are three primary types of navigation in spinal surgery: three-dimensional image-based computer-assisted navigation, robot-assisted navigation, and three-dimensional printed patient-specific drill guides for navigation. All three have demonstrated increased accuracy in placement of spinal instrumentation versus freehand or fluoroscopic-assisted techniques. Each has unique preoperative and intraoperative technical considerations. All three typically rely on three-dimensional imaging and will have varied radiation exposure to the patient and surgical staff based on specific imaging settings used. Navigation options are continually improving and are expected to broaden efficiency, accuracy, and indications in the future.


Gender-based challenges faced by older Sikh women as immigrants: recognizing and acting on the risk of coronary artery disease.
Gender and ethnocultural affiliation can influence people's health beliefs and their ability to make behavioural changes associated with risk reduction. The authors undertook a series of grounded theory studies aimed at describing and explaining how gender and ethnocultural affiliation influence the process that people undergo when faced with the need to make behavioural changes to reduce the risk of coronary artery disease (CAD). Here, they describe the gender-based influences associated with managing CAD risk in a small sample of older Sikh immigrants to Canada. Data were collected through semi-structured interviews, using an interpreter when necessary. Interviews were audiotaped to enable verification of interpretation and transcription. Data were analyzed using constant comparative methods. The core variable that emerged in the series of studies was "meeting the challenge." The process of managing CAD risk included pre-diagnosis or event, liminal or changing self, and living with CAD. Intra-, inter-, and extrapersonal factors as well as sociodemographic characteristics influenced the participants' ability to meet the challenge of managing CAD risk. Health-care providers and policy-makers have a responsibility to work with ethnocultural communities in order to (1) enhance the ability of health-care providers to provide ethnoculturally sensitive care, and (2) develop ethnoculturally relevant resources to enable health promotion and disease prevention. The ultimate aim is to improve health outcomes for Sikh immigrants as vulnerable members of society.


Sensory Modulation Dysfunction in Child Victims of Trauma: a Scoping Review.
Due to the high level of violence globally, providing intervention for child victims of trauma has become a priority for various government departments and health professionals including occupational therapists. Child appropriate sensory modulation intervention, which has its theoretical origins within the occupational therapy profession, has been suggested as a suitable treatment approach for children who are victims of trauma, since the initial experience of trauma occurs on a somatosensory level. Advances in trauma care indicate that children may experience the effects of trauma as an inability to appropriately regulate and organize sensory responses. This results in sensory modulation dysfunction associated with emotional and behavior difficulties. This scoping review provides an overview of the extent to which sensory modulation dysfunction has been identified and treated in child victims of trauma. Using the Arksey and O'Malley (2005) framework, five databases and three manual hand searches were conducted. This scoping review confirmed the scarcity of research available. The 13 studies which met the inclusion criteria indicated that child victims of trauma (CVT) present with a sensory modulation disorder (SMD). Sensory modulation intervention, within the theoretical framework of Ayres Sensory Integration® (ASI®), alone and in combination with psychotherapy approaches was found to be valuable for CVT, in the studies chartered. Identification and treatment of sensory modulation dysfunction in CVT has been researched and is becoming an area of increasing need. Therefore, to remain relevant to the violent contexts within communities, there is a need to expand research in this field.


Functional analysis of the human complement receptor 2 (CR2/CD21) promoter: characterization of basal transcriptional mechanisms.
Human complement receptor (CR) type 2 (CR2/CD21) is a 145-kDa membrane protein encoded within the regulators of complement activation gene cluster localized on human chromosome 1q32. Understanding the mechanisms that regulate CR2 expression is important because CR2 is expressed during specific stages of B cell development, and several lines of evidence suggest a role for altered CR2 function or expression in a number of autoimmune diseases. Additionally, even modest changes in CR2 expression are likely to affect relative B cell responses. In this study we have delineated the transcriptional requirements of the human CR2 gene. We have studied the human CR2 proximal promoter and identified sites important for controlling the level of transcription in CR2-expressing cells. We have determined that four functionally relevant sites lie within very close proximity to the transcriptional initiation site. These sites bind the transcription factors USF1, an AP-2-like transcription factor, and Sp1.


Suicide ideation among recent immigrants: an epidemiological study.
This paper reports preliminary results of an epidemiological survey of suicide ideation among recent adult immigrants from the former Soviet Union to Israel. The study presents one-month prevalence rates of suicide ideation, and the relationship of suicide ideation with demographics, self-rated psychological distress, depression, emotional isolation and social support. Results show that the one-month prevalence rate of suicide ideation in the population is 16.9%. Suicide ideation was most frequent among socially and emotionally isolated immigrants with lower social support. The strongest predictor of suicide ideation for both sexes was level of psychological distress, whereas the severity of depression predicted suicide ideation only in females. The findings can be used as a point of departure for the development of suicide prevention programs.


QbD Approach towards Robust Design Space for Flutamide/PiperineSelf-Emulsifying Drug Delivery System with Reduced Liver Injury.
Flutamide which is used to treat prostate cancer and other diseases induces liver damage during and after the therapy. The aim of this study was to develop a flutamide/piperineco-loaded self-emulsifying drug delivery system (FPSEDDS) to inhibit flutamide-induced liver injury by utilizing piperine as a metabolic inhibitor. The development of SEDDS was carried out following a quality by design (QbD) approach. The risk assessment study was performed to identify critical quality attributes (CQAs) and critical material attributes (CMAs)/critical process parameters (CPPs). I-optimal mixture design was executed with three CMAs as the independent variables and CQAs as the dependable variables. The effectiveness of optimized SEDDS to circumvent flutamide-induced hepatotoxicity was assessed in mice. The numerical optimization suggested an optimal formulation with a desirability value of 0.621, using CQAs targets as optimization goals with 95% prediction intervals (α = 0.05). The optimal formulation exhibited the grade A SEDDS characteristics with the guarantee of high payloads in self-formed oily droplets. The design space was also obtained from the same optimization goals. All CQA responses of verification points were found within the 95% prediction intervals of the polynomial models, indicating a good agreement between actual versus predicted responses within the design space. These obtained responses also passed CQAs acceptance criteria. Finally, hematoxylin-eosin staining revealed the minimal flutamide-induced hepatotoxicity from the optimal SEDDS formulation as compared to the control and flutamide/piperine normal suspension. We demonstrate that the piperine containing optimized SEDDS formulation developed by QbD significantly reduces the flutamide-induced liver injury in mice.


Pulmonary edema following pericardiotomy for cardiac tamponade.
A 57-year-old man with a history of a previous myocardial infarction presented with acute cardiac tamponade due to malignant pericardial effusion. Immediately following emergency surgical drainage of the pericardium by subxiphoid window, acute pulmonary edema developed. The sudden increase in venous return following the release of cardiac compression may result in this rare complication. Gradual removal of pericardial fluid under hemodynamic monitoring is advisable, particularly in patients with preexisting heart disease.


Robotic gastrointestinal surgery: early experience and system description.
Robotic technology has recently been introduced to gastrointestinal laparoscopic surgery. Its addition offers the promise of opening more procedures up to minimally invasive surgery. One system is described and illustrated in detail using antireflux surgery as an example. Seventy patients underwent robotically assisted gastrointestinal surgical procedures. These procedures were antireflux surgery (25), bowel resection (18), cholecystectomy (8), Heller myotomy (5), splenectomy (5), exploratory laparoscopy (4), adrenalectomy (1), pyloroplasty (1), and resection of a gastric mass (1) and duodenal (1) and colonic (1) polyps. Seventeen percent of patients required conversion to either an open or a standard laparoscopic procedure. This early experience with an the first Food and Drug Administration-approved general surgery robotic surgical system showed that it is safe and effective, the system has significant promise.


Microbial biofilms in endodontic infections: an update review.
Biofilms and microbial aggregates are the common mechanisms for the survival of bacteria in nature. In other words, the ability to form biofilms has been regarded as a virulence factor. Microbial biofilms play an essential role in several infectious diseases such as pulp and periradicular pathosis. The aim of this article was to review the adaptation mechanisms of biofilms, their roles in pulpal and periapical pathosis, factors influencing biofilm formation, mechanisms of their antimicrobial resistance, models developed to create biofilms, observation techniques of endodontic biofilms, and the effects of root canal irrigants and medicaments as well as lasers on endodontic biofilms. The search was performed from 1982 to December 2010, and was limited to papers in English language. The keywords searched on Medline were "biofilms and endodontics," "biofilms and root canal irrigation," "biofilms and intra-canal medicament," and "biofilms and lasers." The reference section of each article was manually searched to find other suitable sources of information.


Trypanosoma brucei: ecto-phosphatase activity present on the surface of intact procyclic forms.
The results presented in this paper indicate that procyclic forms of Trypanosoma brucei possess a phosphatase activity detected in the external cell surface able to hydrolyze about 0.7 nmol.mg-1.min-1 p-nitrophenylphosphate. A faster rate of hydrolysis was observed when membrane-enriched fractions were used. This activity is weakly sensitive to 1 mM NaF, 10 mM tartrate and 10 mM levamizole but strongly inhibited by 0.1 mM vanadate. Inhibition by both NaF and vanadate have a competitive character. This phosphatase activity decreases by increasing the pH from 6.8 to 8.4, a pH range in which cell viability was maintained during at least 1 hour. In the membrane-enriched fractions this phosphatase activity showed to be an acid phosphatase. In addition, intact cells could catalyze the dephosphorylation of [32P]phosphocasein phosphorylated at serine and threonine residues.


Development of Guiding Principles for a New Era in Graduate Education.
Many external drivers may be influencing a paradigm shift in graduate education. Workforce dynamics are driving a re-examination of what is instructed in graduate programs as well as how curricula are delivered. Most graduate programs have made incremental changes in their philosophical approaches, but new and more dramatic paradigms may be needed to sufficiently address the future needs of employers and students alike.


Development of a physiologically-based pharmacokinetic model of 2-phenoxyethanol and its metabolite phenoxyacetic acid in rats and humans to address toxicokinetic uncertainty in risk assessment.
2-Phenoxyethanol (PhE) has been shown to induce hepatotoxicity, renal toxicity, and hemolysis at dosages ≥ 400 mg/kg/day in subchronic and chronic studies in multiple species. To reduce uncertainty associated with interspecies extrapolations and to evaluate the margin of exposure (MOE) for use of PhE in cosmetics and baby products, a physiologically-based pharmacokinetic (PBPK) model of PhE and its metabolite 2-phenoxyacetic acid (PhAA) was developed. The PBPK model incorporated key kinetic processes describing the absorption, distribution, metabolism and excretion of PhE and PhAA following oral and dermal exposures. Simulations of repeat dose rat studies facilitated the selection of systemic AUC as the appropriate dose metric for evaluating internal exposures to PhE and PhAA in rats and humans. Use of the PBPK model resulted in refinement of the total default UF for extrapolation of the animal data to humans from 100 to 25. Based on very conservative assumptions for product composition and aggregate product use, model-predicted exposures to PhE and PhAA resulting from adult and infant exposures to cosmetic products are significantly below the internal dose of PhE observed at the NOAEL dose in rats. Calculated MOEs for all exposure scenarios were above the PBPK-refined UF of 25.


[Correlation between levels of fibrinogen, beta455 g/A fibrinogen gene polymorphism and chronic periodontitis].
To investigate the relationship between plasma levels of fibrinogen, the-beta455 G/A fibrinogen gene polymorphism and the severity of periodontal inflammation and to explore the possible role of fibrinogen in the association of periodontitis with coronary heart disease (CHD). A total of 121 patients with moderate to severe periodontitis and periodontally healthy and gingivitis controls were enrolled in the study. Peripheral blood samples were collected and the plasma fibrinogen levels were determined by the clotting method of Clauss. Polymerase chain reaction and restriction fragment length polymorphism analysis with Hae III were used to examine the -beta455 G/A fibrinogen gene polymorphism. Fibrinogen levels were significantly higher in moderately or severely chronic periodontitis patients [(3.45 +/- 0.68) g/L] than periodontally healthy and gingivitis controls [(2.47 +/- 0.42) g/L, P < 0.001]. The carrier status of the A allele at position -455 in the beta fibrinogen gene was associated with elevated fibrinogen levels and the frequency of the-A455 allele in the beta fibrinogen gene in the patient group was significantly higher than in the control group (P = 0.032). Carriers of the -A455 allele were about 3-fold more likely to have moderate or severe periodontitis as compare to individuals without the -A455 allele( OR = 3. =135, P= 0.008). Fg-beta455 G/A polymorphism may contribute to the elevated plasma fibrinogen levels and put individuals at higher risk of having severe periodontitis. As the independent risk factor of CHD, fibrinogen levels and Fg-beta455 G/A polymorphism may play a role in the pathogenesis of periodontitis.


Ethmoidal hematoma in nine horses.
Ethmoidal hematoma was diagnosed in 9 horses by results of physical examination, endoscopy, radiography, and histologic examination of tissues. The horses had stertorous breathing (n = 4) or intermittently sanguineous nasal discharge (n = 7). All horses underwent sinusotomy and extirpation of the lesion. At reexamination 15 to 104 months after surgery (mean, 61 months), 3 horses had recurrence of ethmoidal hematoma, and 1 horse had ethmoidal hematoma involving the contralateral ethmoturbinates. One of the horses with recurrence of ethmoidal hematoma also developed a contralateral lesion; both lesions recurred and additional surgeries were performed.


Synthesis of multilayered alginate microcapsules for the sustained release of fibroblast growth factor-1.
Alginate microcapsules coated with a permselective poly-L-ornithine (PLO) membrane have been investigated for the encapsulation and transplantation of islets as a treatment for type 1 diabetes. The therapeutic potential of this approach could be improved through local stimulation of microvascular networks to meet mass transport demands of the encapsulated cells. Fibroblast growth factor-1 (FGF-1) is a potent angiogenic factor with optimal effect occurring when it is delivered in a sustained manner. In this article, a technique is described for the generation of multilayered alginate microcapsules with an outer alginate layer that can be used for the delivery of FGF-1. The influence of alginate concentration and composition (high mannuronic acid (M) or guluronic acid (G) content) on outer layer size and stability, protein encapsulation efficiency, and release kinetics was investigated. The technique results in a stable outer layer of alginate with a mean thickness between 113 and 164 μm, increasing with alginate concentration and G-content. The outer layer was able to encapsulate and release FGF-1 for up to 30 days, with 1.25% of high G alginate displaying the most sustained release. The released FGF-1 retained its biologic activity in the presence of heparin, and the addition of the outer layer did not alter the permselectivity of the PLO coat. This technique could be used to generate encapsulation systems that deliver proteins to stimulate local neovascularization around encapsulated islets.


Opportunities and challenges of sustainable agricultural development in China.
This paper introduces the concepts and aims of sustainable agriculture in China. Sustainable agricultural development comprises sustainability of agricultural production, sustainability of the rural economy, ecological and environmental sustainability within agricultural systems and sustainability of rural society. China's prime aim is to ensure current and future food security. Based on projections of China's population, its economy, societal factors and agricultural resources and inputs between 2000 and 2050, total grain supply and demand has been predicted and the state of food security analysed. Total and per capita demand for grain will increase continuously. Total demand will reach 648 Mt in 2020 and 700 Mt in 2050, while total grain yield of cultivated land will reach 470 Mt in 2010, 585 Mt in 2030 and 656 Mt in 2050. The per capita grain production will be around 360kg in the period 2000-2030 and reach 470kg in 2050. When productivities of cultivated land and other agricultural resources are all taken into consideration, China's food self-sufficiency ratio will increase from 94.4% in 2000 to 101.3% in 2030, suggesting that China will meet its future demand for food and need for food security. Despite this positive assessment, the country's sustainable agricultural development has encountered many obstacles. These include: agricultural water-use shortage; cultivated land loss; inappropriate usage of fertilizers and pesticides, and environmental degradation.


Sponge-like loose and porous SnO2 microspheres with rich oxygen vacancies and their enhanced room-temperature gas-sensing performance.
Structure and surface modification of semiconductor materials are of great importance in gas sensors. In this study, a facile citric acid-assisted solvothermal method via a precise calcination process was leveraged to synthesize sponge-like loose and porous SnO2 microspheres with rich oxygen vacancies (denoted as LP-SnO2-Ov). When this material was used in a gas sensor, it exhibited an extremely high response to 10 ppm hydrogen sulfide gas at room temperature (Ra/Rg = 9688), which was 54 times higher than that of commercial SnO2. Furthermore, the response time of LP-SnO2-Ov was 5 s, while the recovery time was 177 s. Moreover, it displayed such high selectivity and stability for hydrogen sulfide gas that its properties remained almost unchanged after 1 month. This method paves a new way to fabricate materials possessing a sponge-like loose and porous structure with oxygen vacancies, which is promising for many other scientific fields such as lithium-ion batteries and photocatalysis.


RNA interference is not involved in natural antisense mediated regulation of gene expression in mammals.
Antisense transcription, yielding both coding and non-coding RNA, is a widespread phenomenon in mammals. The mechanism by which natural antisense transcripts (NAT) may regulate gene expression are largely unknown. The aim of the present study was to explore the mechanism of reciprocal sense-antisense (S-AS) regulation by studying the effects of a coding and non-coding NAT on corresponding gene expression, and to investigate the possible involvement of endogenous RNA interference (RNAi) in S-AS interactions. We have examined the mechanism of S-AS RNA base pairing, using thymidylate synthase and hypoxia inducible factor-1alpha as primary examples of endogenous genes with coding and non-coding NAT partners, respectively. Here we provide direct evidence against S-AS RNA duplex formation in the cytoplasm of human cells and subsequent activation of RNAi. Collectively, our data demonstrate that NAT regulation of gene expression occurs through a pathway independent of Dicer associated RNAi. Moreover, we introduce an experimental strategy with utility for the functional examination of other S-AS pair interactions.


Complementary DNA cloning, messenger RNA expression, and induction of alpha-class glutathione S-transferases in mouse tissues.
Glutathione S-transferases (EC 126.96.36.199) are a multigene family of related proteins divided into four classes. Each class has multiple isoforms that exhibit tissue-specific expression, which may be an important determinant of susceptibility of that tissue to toxic injury or cancer. Recent studies have suggested that alpha-class glutathione S-transferase isoforms may play an important role in the development of cancers. Several alpha-class glutathione S-transferase isozymes have been characterized, purified, and cloned from a number of species, including rats, mice, and humans. Here we report on the cloning, sequencing, and mRNA expression of two alpha-class glutathione S-transferases from mouse liver, termed mYa and mYc. While mYa was shown to be identical to the known alpha-class glutathione S-transferase complementary DNA clone pGT41 (W. R. Pearson et al., J. Biol. Chem., 263: 13324-13332, 1988), the other clone, mYc, was demonstrated to be a novel complementary DNA clone encoding a glutathione S-transferase homologous to rat Yc (subunit 2). The mRNA for this novel complementary DNA is expressed constitutively in mouse liver. It also is the major alpha-class glutathione S-transferase isoform expressed in lung. The levels of expression of the butylated hydroxyanisole-inducible form (mYa) are highest in kidney and intestine. Treatment of mice with butylated hydroxyanisole had little effect on the expression levels of mYc but strongly induced mYa expression in liver. Butylated hydroxyanisole treatment increased expression levels for both mYa and mYc to varying degrees in kidney, lung, and intestine. The importance of the novel mouse liver alpha-class glutathione S-transferase isoform (mYc) in the metabolism of aflatoxin B1 and other carcinogens is discussed.


Factors Associated with Unwanted Pregnancy among Adolescents in Russia.
To identify social and behavioral factors associated with unintended pregnancy among adolescents in Russia. Cross-sectional. The investigation group consisted of 145 adolescents aged 15-19 years admitted to a youth-friendly clinic for induced abortion. The control group consisted of 77 sexually active never pregnant adolescent girls of similar age admitted for other reasons. Both groups completed a self-administered questionnaire about their occupation, educational level of their mother, family structure and socioeconomic status, relationship with their mother, sexual behavior, and substance use. Factors associated with unintended pregnancy. In the bivariate analysis pregnant adolescents tended to have a lower educational level, to live in a nonintact family, to prefer stronger alcohol drinks, and to have a younger age at sexual debut and more frequent sexual intercourse. In the log-linear model six factors appeared to be directly linked to pregnancy: mother's lower education, alcohol consumption, nonintact family structure, low academic grades, higher frequency of sexual intercourse, and lower age at sexual debut. Although the issue of unwanted pregnancy and possible ways to prevent it should be kept in mind in the psychosocial assessment of any adolescent, the results of our study suggest that some adolescents are at increased risk of unwanted pregnancy. This group includes adolescent girls with low educational attainment, living in a disrupted family, and reporting other risk behaviors. These adolescents might specially benefit from specific preventive programs to reduce the number of adverse outcomes.


The role of angiotensin II in cognition and behaviour.
Polymorphisms of the renin-angiotensin system are associated with cardiovascular disorders, possibly as a consequence of increased brain angiotensin II activity. Within the brain, angiotensin controls blood pressure, fluid balance and hormone secretion; it also influences behaviour: reduction of central angiotensin function has both antidepressant-like and axiolytic-like actions. Evidence concerning the role of the renin-angiotensin system in learning and memory is contradictory, although more studies support the proposal that angiotensin reduces cognitive function. Studies of renin-angiotensin system genotype and psychological status have suggested an association between the angiotensin-converting enzyme deletion allele and age related cognitive decline, but a greater prevalence of the insertion allele in Alzheimer's disease. The deletion allele has also been associated with depressive illness, as has the M allele of the angiotensinogen gene although other studies have failed to replicate these findings. The role of the brain renin-angiotensin system in human psychopathology remains to be fully explored.


The RING finger protein NtRCP1 is involved in the floral transition in tobacco (Nicotiana tabacum).
The transition from the vegetative phase to the reproductive phase is a major developmental process in flowering plants. The underlying mechanism controlling this cellular process remains a research focus in the field of plant molecular biology. In the present work, we identified a gene encoding the C3H2C3-type RING finger protein NtRCP1 from tobacco BY-2 cells. Enzymatic analysis demonstrated that NtRCP1 is a functional E3 ubiquitin ligase. In tobacco plants, expression level of NtRCP1 was higher in the reproductive shoot apices than in the vegetative ones. NtRCP1-overexpressing plants underwent a more rapid transition from the vegetative to the reproductive phase and flowered markedly earlier than the wild-type control. Histological analysis revealed that the shoot apical meristem of NtRCP1-overexpressing plants initiated inflorescence primordia precociously compared to the wild-type plant due to accelerated cell division. Overexpression of NtRCP1 in BY-2 suspension cells promoted cell division, which was a consequence of the shortened G2 phase in the cell cycle. Together, our data suggest that NtRCP1 may act as a regulator of the phase transition, possibly through its role in cell cycle regulation, during vegetative/reproductive development in tobacco plant.


Trends in the characteristics of DI and SSI disability awardees and duration of program participation.
We analyze the effects of trends in the age and diagnostic mix of new disability awardee cohorts from 1975 through 1993 on expected duration on the Disability Insurance (DI) and Supplemental Security Income (SSI) rolls. The 1975-93 shift toward younger awardees is estimated to increase duration by 1.4 years for DI and about 5 years for SSI. Much of the increase in SSI duration is attributable to the recent influx of childhood awardees. For working age adults, the DI and SSI trends are comparable. We also estimate that about half of the 1975-93 increase in DI duration is explained by the increase in the proportion of younger DI-insured workers. During the 1993-2006 period, the effect of changes in the age mix of DI-insured workers will be reversed. This will moderate, but not eliminate, likely upward pressures on caseloads arising from the anticipated rise in incidence rates and the future effects of past increases in expected duration.


Note: Automated maskless micro-multidomain photoalignment.
We present a fully automated maskless exposure system for the fabrication of microscopic orientational surface alignment patterns. The maskless system allows us to fabricate arbitrary surface patterns over a 2 mm × 2 mm area with a resolution of 2.2 μm. A confocal autofocus system insures accurate and repeatable focus. Microscopic orientational surface patterns have been demonstrated to exhibit a variety of novel functionalities, such as surface alignment multi-stability.