The prognostic relevance of lymph node ratio in patients with oral squamous cell carcinoma treated with neoadjuvant therapy regimen and radical surgery.
This study aims at investigating the prognostic significance of lymph node ratio (LNR) in a cohort of patients with oral squamous cell carcinomas (OSCC), treated with neoadjuvant radiochemotherapy followed by radical surgery. The study included 171 treatment-naive patients with biopsy-proven primary OSCC, being reviewed retrospectively. All patients received a concomitant neoadjuvant radiochemotherapy (RCT) followed by radical surgery of the primary tumor and neck dissection based on the pretreatment staging results. The Kaplan-Meier survival analysis method was used to estimate the events of interest for overall survival (OS). Prognostic factors were identified through univariate and multivariate analysis. The 5-year overall survival rate for all patients was 48 %. In univariate analysis, patient's age and data compiled from the histopathological examination as margin status, extracapsular spread, ypT, ypN, ypUICC, number of positive lymph nodes and lymph node ratio (LNR) had a statistically significant impact on overall survival. Multivariate analysis revealed an independent significant impact of patient age, ypT, margin status and LNR on OS. ypN showed no statistical significant impact on OS. Our results show that LNR is an important predictor for OS in patients with OSCC that were treated with neoadjuvant radiochemotherapy and radical surgery.


Levels of VEGF-A mRNA in plasma from patients with colorectal carcinoma as possible surrogate marker of angiogenesis.
The regulator of angiogenesis most extensively studied is VEGF. VEGF mRNA in plasma from patients with colorectal cancer was analyzed as a possible surrogate marker of tumor angiogenesis. VEGF mRNA was measured by quantitative PCR in plasma, tumors and circulating tumor cells from colorectal cancer patients. Circulating VEGF protein was analyzed by ELISA. Microvessel density was determined. Levels of VEGF mRNA and protein in plasma were higher in patients than in controls. VEGF mRNA was overexpressed in tumors with respect to normal tissues. Levels of VEGF protein were associated with VEGF mRNA in plasma, but no associations with tumor samples were found. A trend to statistical significance was shown between high VEGF mRNA and vascular invasion. MVD was not related to VEGF mRNA in plasma. Thus, VEGF mRNA could be a marker similar to VEGF protein in plasma.


Electropolymerized surface ion imprinting films on a gold nanoparticles/single-wall carbon nanotube nanohybrids modified glassy carbon electrode for electrochemical detection of trace mercury(II) in water.
Electrochemical detection of Hg(II) using a electropolymerized ion imprinting poly(2-mercaptobenzothiazole) films at the surface of gold nanoparticles/single-walled carbon nanotube nanohybrids modified glassy carbon electrode (PMBT/AuNPs/SWCNTs/GCE) is described for the first time. The Hg(II)-imprinted PMBT/AuNPs/SWCNTs/GCE sensor exhibits larger binding to functionalized capacity, larger affinity, faster binding kinetics and higher selectivity to template Hg(II). The differential pulse anodic stripping voltammetry (DPASV) response of the Hg(II)-imprinted PMBT/AuNPs/SWCNTs/GCE sensor to Hg(II) is ca. 3.7- and 10.5-fold higher than that at the non-imprinted PMBT/AuNPs/SWCNTs/GCE and the imprinted PMBT/AuNPs/GCE, respectively, and the detection limit for Hg(II) is 0.08 nM (S/N=3, which is well below the guideline value given by the World Health Organization) and a sensitivity of 0.749 μA nM(-1) was obtained. Excellent wide linear range (0.4-96.0 nM) and good repeatability (relative standard deviation of 2.6%) were obtained for Hg(II). The interference experiments show that Ag(I), Pb(II), Cd(II), Zn(II) and Cu(II) had little or no influence on the Hg(II) signal. These values, particularly the high sensitivity and excellent selectivity in contrast to the values reported previously in the area of electrochemical Hg(II) detection, demonstrate the analytical performance of the Hg(II)-imprinted PMBT/AuNPs/SWCNTs/GCE toward Hg(II) is superior to the existing electrodes and could be used for efficient determination of Hg(II) in natural water samples.


Murine interferon system regulation: isolation and characterization of a mutant 3T6 cell engaged in the semiconstitutive synthesis of interferon.
We describe the isolation and characterization of a virus-resistant mutant of murine 3T6 cells. The mutant, designated 3T6-VrB2, displays a high degree of resistance to infection by members of the toga-, rhabdo- and picornavirus classes. The level of this resistance to infection is similar to the parent 3T6 pretreated with approximately 100 lU/ml of interferon. Upon co-cultivation of 3T6-VrB2 cells with interferon-sensitive mouse cells, an antiviral state is induced in the latter cells as measured by a reduction of virus yield following infection. The nature of the induction is defined by a series of experiments using anti-mouse interferon antiserum. In the presence of this antiserum, the ability of the mutant to induce an antiviral state in interferon-sensitive mouse cells upon co-cultivation is eliminated. Additionally, growth of the mutant cells in the presence of this antiserum causes a reversal of the virus-resistant phenotype. Our results indicate that 3T6-VrB2 contains a mutation affecting the regulation of the murine interferon system such that the cell is engaged in the semiconstitutive synthesis of interferon.


Manganese-Catalyzed Asymmetric Hydrogenation of Quinolines Enabled by π-π Interaction*.
The non-noble metal-catalyzed asymmetric hydrogenation of N-heteroaromatics, quinolines, is reported. A new chiral pincer manganese catalyst showed outstanding catalytic activity in the asymmetric hydrogenation of quinolines, affording high yields and enantioselectivities (up to 97 % ee). A turnover number of 3840 was reached at a low catalyst loading (S/C=4000), which is competitive with the activity of most effective noble metal catalysts for this reaction. The precise regulation of the enantioselectivity were ensured by a π-π interaction.


A monoclonal antibody against the type II isotype of beta-tubulin. Preparation of isotypically altered tubulin.
Mammalian brain tubulin consists of several isotypes of alpha and beta subunits that separate on polyacrylamide gels into three electrophoretic classes, designated alpha, beta 1, and beta 2. It has not been possible hitherto to resolve the different isotypes in a functional form. To this end, we have now isolated a monoclonal antibody, using as an immunogen a chemically synthesized peptide corresponding to the carboxyl-terminal sequence of the major tubulin isotype (type II) found in the beta 1-tubulin electrophoretic fraction. The antibody binds to beta 1 but not to alpha or beta 2. When pure tubulin from bovine brain is passed through an immunoaffinity column made from the anti-type II antibody, the tubulin that elutes in the unbound fraction is enriched greatly for the beta 2 electrophoretic variant. The tubulin that binds to the column appears to contain only alpha and beta 1, not beta 2. When these tubulin fractions are characterized by immunoblotting using the anti-type II antibody, the antibody binds only to the beta 1 band in the bound fraction, not to the beta 1 band in the unbound fraction. Using polyclonal antibodies generated against the carboxyl-termini of types I, III, and IV, we demonstrate that the beta 1 electrophoretic species is comprised of isotypes I, II, and IV, whereas the beta 2 variant is comprised exclusively of type III beta-tubulin. Further, we calculate that beta-tubulin in purified bovine brain tubulin is comprised of 3% type I, 58% type II, 25% type III, and 13% type IV tubulins.


Molecular probes of the vestibular nerve. I. Peripheral termination patterns of calretinin, calbindin and peripherin containing fibers.
Vestibular afferents have different physiological properties that can be at least partially correlated with the morphology that the peripheral ending makes with type I and type II hair cells. If the location of the ending in the sensory epithelium is included, the correlations are further improved. It is also known that vestibular afferents can be immunohistochemically stained for a variety of different substances. We have concentrated on three of these markers, calretinin, calbindin and peripherin, because the sources of afferents to the vestibular nuclear complex that contain these substances are restricted, in two cases to the primary afferents. We demonstrate that calretinin is found only in the calyx-only afferents that are located at the apex of the cristae ampullaris and along the striola of the maculae. The area containing stained calyces is equal to or slightly smaller than the central zone of the cristae as defined by the Goldberg group [J. Neurophysiol. 60 (1988) 167]. Calbindin is also found in calyces at the apex of the cristae and along the striola of the otoliths. Examination of adjacent sections of all endorgans indicates that calbindin staining overlaps with calretinin, but is always several hair cells wider on each side. Peripherin also stains fibers in the neuroepithelium. The greatest density of staining is in the peripheral zone of the cristae, i.e. at the base and toward the planum semilunatum. We suggest that these substances are useful markers for specific sets of vestibular afferents.


The calcium sensing receptor modulates fluid reabsorption and acid secretion in the proximal tubule.
The proximal tubule uses a complex process of apical acid secretion and basolateral bicarbonate absorption to regulate both luminal acidification and fluid absorption. One of the primary regulators of apical acid secretion is the luminal sodium-hydrogen exchanger expressed along the apical membrane of the proximal tubule. Similarly, the calcium-sensing receptor (CaSR) is also located along the luminal membrane of the proximal tubule. Here we investigated the role of CaSR in proton secretion and fluid reabsorption in proximal tubules by modulating luminal calcium concentration, using both in vivo micropuncture in rats and in vitro perfused mouse proximal tubules. Using CaSR knockout mice and a calcimimetic agent, we found that increased proton secretion and fluid reabsorption were CaSR dependent. Activating CaSR by either raising the luminal calcium ion concentration or by the calcimimetic caused a concomitant increase in sodium-dependent proton extrusion and fluid reabsorption, whereas in proximal tubules isolated from CaSR knockout mice varying calcium ion concentration had no effect. Application of a calcimimetic in lower concentrations of calcium ion stimulated these processes in vitro and in vivo. Thus, in both rats and mice, increased luminal calcium concentration leads to enhanced fluid reabsorption in the proximal tubule, a process related to activation of CaSR.


Photodynamic therapy with zinc-tetra(p-sulfophenyl)porphyrin bound to cyclodextrin induces single strand breaks of cellular DNA in G361 melanoma cells.
The basis of photodynamic therapy (PDT) is the phototoxicity resulting from co-action of light, sensitizer and oxygen. In this study we demonstrate in vitro phototoxicity measurement on G361 cell lines using ZnTPPS(4) sensitizer bound to cyclodextrin hpbetaCD. We have proved its photodamage effect on cancer cell lines in the visible region of spectrum. We used the halogen lamp (24V/250W) as a source of radiation. After 24h incubation of cell cultures with 10 microM ZnTPPS(4) and 1mM cyclodextrine hpbetaCD, the cells were irradiated for 7.5 min at the total irradiation dose of 12.5 Jcm(-2). Analysis of DNA damage in the cell line after PDT was proved by comet assay and using inversion fluorescent microscope with image analysis. This treatment method gave rise to DNA damage. The used radiation dose of visible light in the absence of sensitizers does not induce DNA breaks in tumour cells. In conclusion, binding of ZnTPPS(4) sensitizer to cyclodextrin hpbetaCD may improve the efficacy of PDT for the treatment of malign melanoma.


Usefulness of right ventricular tissue Doppler imaging for diagnosis of right ventricular myocardial infarction.
Right ventricular myocardial infarction (RVMI) is a complication of acute inferior myocardial infarction and sometimes causes severe hemodynamic disturbance. It is therefore important to promptly detect RVMI and assess the severity of right ventricular (RV) dysfunction. Tissue Doppler imaging (TDI) is a useful method to assess left ventricular function and RV function. In this study, we investigated the possibility of diagnosing RVMI using tricuspid annular velocity determined by TDI. Thirty consecutive patients with first acute inferior myocardial infarction were studied. The diagnosis of RVMI was based on an ST-segment elevation of at least 0.1 mV in lead V4R. The patients were classified into 12 patients with RVMI (the RVMI group) and 18 patients without RVMI (non-RVMI group). All patients underwent two-dimensional echocardiography, pulsed Doppler and TDI, and coronary angiography within 48 h after onset of myocardial infarction. Tricuspid inflow velocity was recorded by pulsed Doppler and early diastolic tricuspid inflow velocity (TVE) was measured. Peak early diastolic velocity of the tricuspid annulus (TVe') at the RV free wall was recorded using TDI. The ratio of TVE to TVe' (TVE/TVe') was calculated. TVe' was significantly lower in the RVMI group compared to that in the non-RVMI group (5.9 ± 1.3 vs. 9.1 ± 3.1; p = 0.0025). On the basis of a TVe' cutoff value of less than 8.3 cm/s, RVMI was diagnosed with 100 % sensitivity and 61 % specificity. The early diastolic tricuspid annular velocity determined by TDI is a noninvasive and sensitive index for diagnosing RVMI.


Werner Syndrome Protein Expression in Breast Cancer.
Werner protein (WRN) plays an important role in DNA repair, replication, transcription, and consequently genomic stability via its DNA-helicase and exonuclease activity. Loss of function of WRN is associated with Werner syndrome (WS), which is characterized by premature aging and cancer predisposition. Malignancies that are commonly linked to WS are thyroid carcinoma, melanoma, breast cancer, meningioma, and soft tissue and bone sarcomas. Currently, the clinicopathologic significance of WRN in breast cancer is largely unknown. We investigated the clinicopathologic and prognostic significance of WRN protein expression in a cohort of clinically annotated series of sporadic (n = 1650) and BRCA-mutated (n = 75) invasive breast cancers. We correlated WRN protein expression to clinicopathologic characteristics, DNA repair protein expression, and survival outcomes. There is strong evidence of association between low nuclear and cytoplasmic WRN co-expression and low levels of KU70/KU80, DNA-PK, DNA Pol-B, CKD18, cytoplasmic RECQL4, and nuclear BLM protein expression (adjusted P-values < .05). Tumors with low nuclear or cytoplasmic WRN expression have worse overall breast cancer-specific survival (BCSS) (adjusted P-values < .05). In topoisomerase I overexpressed tumors, low WRN nuclear expression was associated with poor BCSS (P-value < .05). In BRCA-mutated tumors, low WRN cytoplasmic expression conferred shortest BCSS (P < .05). Low WRN protein expression is associated with poor BCSS in patients with breast cancer. This can be used to optimize the risk stratification for personalized treatment.


Verbal memory and semantic clustering in right brain-damaged patients.
Twenty-four right brain-damaged patients without ostensive signs of intellectual impairment or disturbances of verbal comprehension, and 20 normal control subjects were given two lists of words, one (the Rey's Auditory) in which 15 words were semantically unrelated and a second in which 15 two-syllable words belonged to one of three categories. The results demonstrated no difference between the two subject groups, either in the immediate or the delayed recall sections of the Rey's test. The immediate recall section of the semantic verbal memory task, on the contrary, showed significantly poor performance by the right brain-damaged patients. These results suggest an impairment of semantic clustering processes after right hemisphere damage.


Correlation Between β-Glucan and Neutrophil/Eosinophil Ratio of Paranasal Sinus Mucosa and Blood in the Diagnosis of Chronic Fungal Rhinosinusitis.
Chronic fungal rhinosinusitis is a major health problem because of the large impact on quality of life and difficult medical treatment. Its prevalence is increasing. There is currently an opportunity to establish the diagnosis without invasive intervention by utilizing β-glucan, which is the largest component of fungal cell wall and neutrophil/eosinophil ratio (NER). We sought to discover the correlation between β-glucan level and the NER of paranasal sinuses mucosa and blood as a potential diagnostic marker for patients with chronic fungal rhinosinusitis. We conducted a cross-sectional study involving 20 subjects. Blood sampling and maxillary sinus surgery were performed, and fungal identification in the sinus mucosa was determined using the polymerase chain reaction. If a fungal species with β-glucan was found, then the examination was continued with the measurement of β-glucan by enzyme-linked immunosorbent assay, neutrophil, and eosinophil flow cytometry in sinus mucosa and blood. Aspergillus flavus is the most commonly found fungus. All subjects passed the positive β-glucan limit (3 80 pg/mL) of the mucosal sample and only one subject had intermediate results (60-79 pg/mL) from their blood sample. Seventeen subjects had mucosal eosinophilic inflammation whereas the blood of 12 subjects revealed neutrophilic inflammation. There was no significant difference between the level of β-glucan in blood and mucosal sinus (p = 0.886), so that β-glucan examination of blood can describe β-glucan levels in paranasal sinuses. There was a significant difference between mucosal NER and blood (p < 0.001). β-glucan level with NER in both paranasal sinus mucosa and blood had no significant correlation (p > 0.050). β-glucan can be used to establish the diagnosis of chronic fungal rhinosinusitis. However, differential diagnosis of allergy or infection cannot be excluded by examination of blood NER. Still, it is hoped that the process of diagnosis can be obtained quickly and precisely without the need for invasive procedure although it requires more research, especially related to the diagnostic test.


Barriers to support for new graduated nurses in clinical settings: A qualitative study.
New graduated nurses often find the transition to registered nurse a traumatic experience and studies suggest that within some countries this process is inadequately supported. The reasons for this inadequacy remain unclear. The current study was conducted to identify barriers impeding the provision of support to new graduated nurses in clinical settings within Iran. This is a qualitative study conducted through unstructured and semi-structured interviews with 18 licensed nurses (experienced nurses) recruited through purposive sampling. Data were collected at various hospital centers in Iran. All interviews were recorded and transcribed and analysis was completed through the use of content analysis. Barriers to support new graduated nurses included a lack of support-seeking behaviors, management weaknesses, ineffective communication, personal characteristics, and cultural barriers. Understanding the problems and barriers likely to prevent goal attainment is an important step toward reaching those goals. The present study provides a greater and more focused understanding of the barriers impeding the support of new graduated nurses within clinical settings. These barriers mainly include deficiencies in the organizational structure, management, and personal characteristics of colleagues and new graduated nurses. This study will have been a successful undertaking if it can help resolve these barriers.


A 2022 Survey of Commercially Available Smartphone Apps for Sleep: Most Enhance Sleep.
Commercially available smartphone apps represent an ever-evolving and fast-growing market. Our review systematically surveyed currently available commercial sleep smartphone apps to provide details to inform both providers and patients alike, in addition to the healthy consumer market. Most current sleep apps offer a free version and are designed to be used while awake, prior to sleep, and focus on the enhancement of sleep, rather than measurement, by targeting sleep latency using auditory stimuli. Sleep apps could be considered a possible strategy for patients and consumers to improve their sleep, although further validation of specific apps is recommended.


ADP-ribosylation suppresses phosphorylation of the L-type pyruvate kinase.
L-type pyruvate kinase (EC 18.104.22.168) purified from pig liver was ADP-ribosylated by incubation with NAD and ADP-ribosyltransferase purified from hen liver nuclei. Maximal incorporation of the ADP-ribose moiety from NAD into the L-type pyruvate kinase was 0.98 mol/mol of subunit. The Km values for NAD and L-type pyruvate kinase were 0.17 mM and 9.7 microM, respectively. ADP-ribosylation of the L-type pyruvate kinase resulted in suppression of the subsequent phosphorylation catalyzed by cAMP-dependent protein kinase. The ADP-ribosylation-induced suppression of phosphorylation of the L-type pyruvate kinase also resulted in suppression of the phosphorylation-induced inactivation. Amino acid analysis, after exhaustive sequential digestion of ADP-ribosyl-L-type pyruvate kinase with pepsin, aminopeptidase M and carboxy-peptidase B showed arginine to be the ADP-ribose-accepting amino acid. These results together with finding of the ADP-ribosyltransferase activity in mammalian liver cytosol (Moss, J. and Stanley, S.J. (1981) J. Biol. Chem. 256, 7830-7833) suggest that ADP-ribosylation may participate in the regulation of the L-type pyruvate kinase activity through changes in the rate of phosphorylation.


Association of Cellulytic Enzyme Activities in Eucalyptus Mulches with Biological Control of Phytophthora cinnamomi.
ABSTRACT A series of samples were taken from mulched and unmulched trees starting at the surface of mulch or soil to a 15 cm soil depth, forming a vertical transect. Saprophytic fungi isolated from the soil samples on rose bengal medium and surveyed visually were most abundant in mulches and at the interface of mulch and soil (P < 0.05). Microbial activity as assayed by the hydrolysis of fluorescein diacetate was significantly greater in mulch layers than in soils. Cellulase and laminarinase enzyme activities were greatest in upper mulch layers and rapidly decreased in soil layers (P < 0.05). Enzyme activities against Phytophthora cinnamomi cell walls were significantly greater in mulch than in soil layers. When Phytophthora cinnamomi was incubated in situ at the various transect depths, it was most frequently lysed at the interface between soil and mulch (P < 0.001). Roots that grew in mulch layers were significantly less infected with Phytophthora cinnamomi than roots formed in soil layers. In mulched soil, roots were commonly formed at the mulch-soil interface where Phytophthora populations were reduced, whereas roots in unmulched soil were numerous at the 7.5 cm depth where Phytophthora cinnamomi was prevalent. Enzyme activities were significantly and positively correlated with each other, microbial activity, and saprophytic fungal populations, but significantly and negatively correlated with Phytophthora recovery.


Determination of pesticide residues in wine by membrane-assisted solvent extraction and high-performance liquid chromatography-tandem mass spectrometry.
The determination of pesticides in food products is an essential issue to guarantee food safety and minimise health risks of consumers. A protocol based on membrane-assisted solvent extraction and liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) that allows the determination of 18 pesticides in red wine at minimum labour effort for sample preparation was developed and validated. Ten millilitres of wine were extracted using 100 μL of toluene filled in a non-porous polyethylene membrane bag which is immersed in the wine sample. After 150 min extraction under stirring, an aliquot of the extraction solution is analysed using HPLC-MS/MS. The limits of quantification ranged from 3 ng/L for Pirimicarb to 1.33 μg/L for Imidacloprid. Quantification by matrix-matched calibration provided relative standard deviations ≤16 % for most of the target pesticides. The linearity of calibration was given over three to four orders of magnitude, which enables the reliable measurement of a broad range of pesticide concentrations, and for each target pesticide, the sensitivity of the protocol meets the maximum residue levels set by legislations at least for wine grapes. Good agreement of results was found when the new method was compared with a standard liquid-liquid extraction protocol. In five wine samples analysed, Carbendazim and Metalaxyl were determined at micrograms per litre concentrations, even in some of the organic wines. Tebuconazol and Cyprodinitril were determined at lower abundance and concentration, followed by Spiroxamin and Diuron.


Court rejects appeal for safe supply of medical marijuana.
As previously reported, in a May 1999 decision in Wakeford v Canada, the Ontario Superior Court of Justice granted an HIV-positive man an "interim constitutional exemption" from the provisions in the Controlled Drugs and Substances Act that make it an offence to possess or to produce or cultivate marijuana.


Superficial Temporal Artery-Posterior Cerebral Artery Bypass Through Zygomatic Anterior Temporal Approach for Complex Posterior Cerebral Artery Aneurysm.
Posterior cerebral artery (PCA) aneurysms are rare, and most are giant, dissecting, or fusiform in morphology. Proximal occlusion of the PCA without revascularization causes high risk of ischemic complications. This study aimed to evaluate the safety and validity of using superficial temporal artery (STA)-PCA bypass through zygomatic anterior temporal approach in complex PCA aneurysms. Trapping or resecting of aneurysms and reconstruction of distal PCA through a zygomatic anterior temporal approach were performed in 6 patients from June 2017 to August 2020. Postoperative angiography confirmed obliteration of aneurysms and patency of bypass artery. Neurological function was assessed by the modified Rankin Scale (mRS). Patients were 4 men and 2 women with a mean age of 43.8 years (range, 21-58 years). Subarachnoid hemorrhage occurred in 5 patients. Hunt and Hess grade was IV in 3 patients, III in 2 patients, and I in 1 patient. All PCA aneurysms were treated with trapping or resection of the aneurysms and revascularization of distal PCA. Postoperatively, all aneurysms were eliminated, and no new permanent neurological deficit was found. During follow-up, mRS score of all patients improved: 2 patients had mRS score 0, 1 patient had mRS score 1, 1 patient had mRS score 3, and 2 patients had mRS score 4. Long-term graft patency rate was 100%. STA-PCA bypass appears to be safe and effective for the treatment of complex PCA aneurysms requiring supplementation of blood flow in the area of the PCA. We established a surgical route, allowing the procedure to be done through the zygomatic anterior temporal approach. This approach provides adequate operative field exposure and reduces retraction of temporal lobe.


Utility of exercise testing to assess athletes for post COVID-19 myocarditis.
This study assessed a functional protocol to identify myocarditis or myocardial involvement in competitive athletes following SARS-CoV2 infection. We prospectively evaluated competitive athletes (n = 174) for myocarditis or myocardial involvement using the Multidisciplinary Inquiry of Athletes in Miami (MIAMI) protocol, a median of 18.5 (IQR 16-25) days following diagnosis of COVID-19 infection. The protocol included biomarker analysis, ECG, cardiopulmonary stress echocardiography testing with global longitudinal strain (GLS), and targeted cardiac MRI for athletes with abnormal findings. Patients were followed for median of 148 days. We evaluated 52 females and 122 males, with median age 21 (IQR: 19, 22) years. Five (2.9%) had evidence of myocardial involvement, including definite or probable myocarditis (n = 2). Three of the 5 athletes with myocarditis or myocardial involvement had clinically significant abnormalities during stress testing including ventricular ectopy, wall motion abnormalities and/or elevated VE/VCO2, while the other two athletes had resting ECG abnormalities. VO2max, left ventricular ejection fraction and GLS were similar between those with or without myocardial involvement. No adverse events were reported in the 169 athletes cleared to exercise at a median follow-up of 148 (IQR108,211) days. Patients who were initially restricted from exercise had no adverse sequelae and were cleared to resume training between 3 and 12 months post diagnosis. Screening protocols that include exercise testing may enhance the sensitivity of detecting COVID-19 related myocardial involvement following recovery from SARS-CoV2 infection.


Role of surgery in patients with focally progressive gastrointestinal stromal tumors resistant to imatinib.
The benefits of surgery for focally progressive gastrointestinal stromal tumor (GIST) during imatinib therapy are still in discussion. The aim of this study was to compare the outcomes of surgical resection of progressive lesions following tyrosine kinase inhibitor (TKI) therapy (S group) or TKI therapy alone (NS group) in GIST patients. We retrospectively investigated 57 patients with focally progressive GIST during imatinib therapy who were treated in Zhongshan hospital, Fudan University. Progression-free survival (PFS) and overall survival (OS) in the S group were significantly longer than those in the NS group. Among S group, the patients with R0 resection showed longer PFS than R2 resection; however, no difference was found between these two groups. Moreover, PFS and OS were not different in the NS-S group compared with S group. On multivariate analysis, surgery is an independent prognostic factor for longer PFS and OS. Our study supports the decision of treating GIST patients who were focally resistant to imatinib with surgery resection based on its benefit.


Entrainment of the circadian rhythm in the rat pineal N-acetyltransferase activity by prolonged periods of light.
Entertainment of the circadian rhythm in the pineal N-acetyltranferase activity by prolonged periods of light was studied in rats synchronized with a light:dark regime of 12:12 h by observing phase-shifts in rhythm after delays in switching off the light in the evening or after bringing forward of the morning onset of light. When rats were subjected to delays in switching off the light of up to 10 h and then were released into darkness, phase-delays of the evening N-acetyltransferase rise during the same night corresponded roughly to delays in the light switch off. However, phase-delays of the morning decline were much smaller. After a delay in the evening switch off of 11 h, no N-acetyltransferase rhythm was found in the subsequent darkness. The evening N-acetyltransferase rise was phase-delayed by 6.2 h at most 1 day after delays. Phase-delays of the morning N-acetyltransferase decline were shorter than phase-delays of the N-acetyltransferase rise by only 0.7 h to 0.9 h at most. Hence, 1 day after delays in the evening switch off, the period of the high night N-acetyltransferase activity may be shortened only slightly. The N-acetyltransferase rhythm was abolished only after a 12 h delay in switching off the light. Rats were subjected to a bringing forward of the morning light onset and then were released into darkness 4 h before the usual switch off of light. In the following night, the morning N-acetyltransferase decline, but not the evening rise, was phase advanced considerably. Moreover, when the onset of light was brought forward to before midnight, the N-acetyltransferase rise was even phase-delayed. Hence, 1 day after bringing forward the morning onset of light, the period of the high night N-acetyltransferase activity may be drastically reduced. When rats were subjected to a 4 h light pulse around midnight and then released into darkness, the N-acetyltransferase rhythm in the next night was abolished. The data are discussed in terms of a two-component pacemaker controlling the N-acetyltransferase rhythm. It is suggested that delays in the evening switch off of light may disturb the N-acetyltransferase rhythm the next day only a little, as the morning component may adjust to phase-delays of the evening component almost within one cycle.(ABSTRACT TRUNCATED AT 400 WORDS)


Maternal uniparental disomy of chromosome 16 in a case of spontaneous abortion.
To investigate the involvement of uniparental disomies (UPDs) in spontaneous abortions, we analyzed in detail the polymorphism of microsatellites on each chromosome in cases of abortion. Of the 52 spontaneous abortions investigated, 25 had a normal karyotype. The polymorphic analysis of these cases revealed that, in the villi from 24 of the 25 cases, biparental patterns were present in informative microsatellites in all autosomes. In the remaining case with a 46,XX karyotype (case 18), however, the informative patterns of the microsatellites of chromosome 16 appeared to be both of maternal origin. The results also showed that the region from the distal end of the short arm to near the middle point of the long arm of chromosome 16 (pter to D16S3107) were heterozygous, and those of the remaining region of the long arm (D16S3018 to qter) were homozygous. That is, this fetus had maternal isodisomy and heterodisomy of chromosome 16, originating from a maternal, meiosis I non-disjunction of dyad 16 that accompanied a crossover at near the middle point of the long arm. The present finding suggests that some UPDs may become a cause for spontaneous abortions.


Differential effects of soluble and immobilized fibronectins on aortic endothelial cell proliferation and attachment.
We studied the effects of soluble and immobilized forms of plasma fibronectin on bovine aortic endothelial cell (AEC) proliferation and attachment. Soluble fibronectin stimulated AEC growth at 10 micrograms/ml, but at higher concentrations of soluble fibronectin AEC growth was progressively inhibited. The growth rates of arterial smooth muscle cells (ASMC) and dermal fibroblasts (DF) were not altered by soluble fibronectin concentrations of 10 to 100 micrograms/ml. Plasma fibronectin, immobilized by attachment to culture dish surfaces, had no significant effects on the proliferation of any of the cell types examined. The attachment rates of AEC were decreased in the presence of 50 micrograms/ml soluble fibronectin. Immobilized fibronectin increased the rate of AEC attachment, but had no significant effects on ASMC or DF attachment; however, 12 h after plating there was nearly 100% attachment in all groups, whether or not fibronectin was present in the system. That soluble and immobilized fibronectins elicit disparate cellular responses is consistent with published reports of different cell surface receptors for different forms of the protein; in this manner, cells enmeshed in an interstitial matrix containing immobilized fibronectin could still respond to soluble fibronectin in the extracellular milieu.


Neighborhood Socioeconomic Deprivation and Weight Change in a Large U.S. Cohort.
Both excessive weight gain and weight loss are important risk factors in the older population. Neighborhood environment may play an important role in weight change, but neighborhood effects on weight gain and weight loss have not been studied separately. This study examined the associations between neighborhood socioeconomic deprivation and excessive weight gain and weight loss. This analysis included 153,690 men and 105,179 women (aged 51-70 years). Baseline addresses were geocoded into geographic coordinates and linked to the 2000 U.S. Census at the Census tract level. Census variables were used to generate a socioeconomic deprivation index by principle component analysis. Excessive weight gain and loss were defined as gaining or losing >10% of baseline (1995-1996) body weight at follow-up (2004-2006). The analysis was performed in 2015. More severe neighborhood socioeconomic deprivation was associated with higher risks of both excessive weight gain and weight loss after adjusting for individual indicators of SES, disease conditions, and lifestyle factors (Quintile 5 vs Quintile 1: weight gain, OR=1.36, 95% CI=1.28, 1.45 for men and OR=1.20, 95% CI=1.13, 1.27 for women; weight loss, OR=1.09, 95%% CI=1.02, 1.17 for men and OR=1.23, 95% CI=1.14, 1.32 for women). The findings were fairly consistent across subpopulations with different demographics and lifestyle factors. Neighborhood socioeconomic deprivation predicts higher risk of excessive weight gain and weight loss.


Low pH-responsive proteins revealed by a 2-DE based MS approach and related physiological responses in Citrus leaves.
Rare data are available on the molecular responses of higher plants to low pH. Seedlings of 'Sour pummelo' (Citrus grandis) and 'Xuegan' (Citrus sinensis) were treated daily with nutrient solution at a pH of 2.5, 3, or 6 (control) for nine months. Thereafter, we first used 2-dimensional electrophoresis (2-DE) to investigate low pH-responsive proteins in Citrus leaves. Meanwhile, we examined low pH-effects on leaf gas exchange, carbohydrates, ascorbate, dehydroascorbate and malondialdehyde. The objectives were to understand the adaptive mechanisms of Citrus to low pH and to identify the possible candidate proteins for low pH-tolerance. Our results demonstrated that Citrus were tolerant to low pH, with a slightly higher low pH-tolerance in the C. sinensis than in the C. grandis. Using 2-DE, we identified more pH 2.5-responsive proteins than pH 3-responsive proteins in leaves. This paper discussed mainly on the pH 2.5-responsive proteins. pH 2.5 decreased the abundances of proteins involved in ribulose bisphosphate carboxylase/oxygenase activation, Calvin cycle, carbon fixation, chlorophyll biosynthesis and electron transport, hence lowering chlorophyll level, electron transport rate and photosynthesis. The higher oxidative damage in the pH 2.5-treated C. grandis leaves might be due to a combination of factors including higher production of reactive oxygen species, more proteins decreased in abundance involved in antioxidation and detoxification, and lower ascorbate level. Protein and amino acid metabolisms were less affected in the C. sinensis leaves than those in the C. grandis leaves when exposed to pH 2.5. The abundances of proteins related to jasmonic acid biosynthesis and signal transduction were increased and decreased in the pH 2.5-treated C. sinensis and C. grandis leaves, respectively. This is the first report on low pH-responsive proteins in higher plants. Thus, our results provide some novel information on low pH-toxicity and -tolerance in higher plants.


Food intake, locomotor activity, and egg laying in zebra finches: contributions to reproductive energy demand?
We tested two alternative hypotheses: (1) that energy costs of egg production in a small, short-lived passerine, the zebra finch (Taeniopygia guttata), are additive to the animal's total energy budget and are met by an increase in food intake or (2) that birds compensate for the energy costs of egg production by reducing energy expended on locomotor activity, thus, reallocating, but not increasing, their total energy budget. Breeding pairs of zebra finches had 8% lower daily food intake than nonbreeding pairs. Among breeding pairs, food intake varied with stage of egg formation but was lowest during egg laying, when egg formation costs were predicted to be highest. Female feeding behaviour (number of feeding bouts, peck rate) did not vary significantly during the laying cycle. Clutch size, but not egg size, was negatively correlated with food intake; that is, daily food intake was lowest for pairs in which females laid the largest clutches. Breeding pairs had much lower locomotor activity levels (114 hops h-1) than nonbreeding pairs (214 hops h-1), and activity declined sharply from 177 hops h-1 during the prelaying period to 106 hops h-1 at the start of the yolk-formation period. Clutch size was negatively correlated with locomotor activity on the day of peak energy demand for laying; that is, daily locomotor activity level was lowest for pairs in which females laid the largest clutches. Therefore, females reduced activity but did not increase food intake during the laying cycle, despite the additional energy requirements of egg production. These data suggest that the prevailing view of small passerines as "classic" income breeders needs to be reevaluated.


Effects of buprenorphine maintenance dose on mu-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers.
The clinical effectiveness of opioid maintenance for heroin dependence is believed to result from a medication's ability to decrease mu-opioid receptor (muOR) availability thereby replacing agonist effects, alleviating withdrawal symptoms and attenuating heroin effects. We empirically tested this hypothesis in five heroin-dependent volunteers who were successively maintained on 32, 16, 2, and 0 mg daily buprenorphine (BUP) tablet doses. We predicted and confirmed that higher BUP doses would decrease in vivo muOR availability (measured with PET and [(11)C]carfentanil), increase plasma levels of BUP and its metabolite nor-BUP, and decrease withdrawal symptoms and hydromorphone (HYD) responses. Relative to placebo, BUP significantly decreased mean (+/-SEM) whole-brain muOR availability 41+/-8, 80+/-2, and 84+/-2% at 2, 16, and 32 mg, respectively. Regions of interest (ROIs) (prefrontal cortex, anterior cingulate, thalamus, amygdala, nucleus accumbens, caudate) showed similar dose-dependent effects. Changes in muOR availability varied across ROIs (prefrontal cortex, 47% vs amygdala, 27%) at BUP 2 mg, but were more homogeneous across ROIs at BUP 32 mg (94-98%; except thalamus, 88%). Relative to placebo (0 ng/ml), peak plasma levels of BUP and nor-BUP were comparable and dose-dependent (0.5-1, 5-6, and 13-14 ng/ml at 2, 16, and 32 mg, respectively). muOR availability decreases were negatively correlated with BUP plasma level and positively correlated with questionnaire-based opioid withdrawal symptoms and attenuation of HYD symptoms. These findings suggest that high-dose BUP maintenance produces near-maximal muOR occupation, muOR availability correlates well with plasma levels, and BUP-related opioid symptoms and antagonist blockade exhibit concentration-effect relationships.


Pigmentary mosaicism in hypomelanosis of Ito. Further evidence for functional disomy of Xp.
We report on a female with mental and motor retardation, facial dysmorphism, abnormal pigmentation reminiscent to hypomelanosis of Ito (HI), and karyotypic mosaicism involving a small supernumerary marker chromosome. The marker chromosome was defined by fluorescence in situ hybridisation (FISH) as a ring X chromosome with breakpoints in the juxtacentromeric region. FISH analysis showed that the ring does not include the XIST locus at the X-inactivation centre and, therefore, may not be subject to X inactivation. X-inactivation studies with the HUMARA (human androgen receptor) and FMR1 assay showed a skewed X-inactivation pattern (85:15) with preferential inactivation of the paternal X chromosome. These results are discussed with respect to the role of functional disomy of Xp in the pathogenesis of HI.


Cotinine ameliorates memory and learning impairment in senescent mice.
This study aimed to assess the effects of cotinine on age-induced memory and learning impairment and related downstream pathways in mice. Thirty aged (18-month old) and 10 young mice (8-week old) were randomly divided into 4 groups (n = 10 each) and subjected to cotinine at 5 mg/kg dose and/or methyllycaconitine (MLA) at 1 mg/kg, i.p. dose (α7 nAChRs antagonist) for 4 weeks. Morris water maze (MWM) and novel object recognition (NOR) tasks were used to assess spatial and recognition learning and memories of the mice, respectively. Levels of oxidative stress, apoptosis, neuroinflammation, and structural synaptic plasticity, and also neurotrophic factors and α7 nAChRs were assessed in the hippocampus using either ELISA or Western blotting. Aging was associated with learning and memory disabilities and dysregulation of the assessed pathways in the hippocampus of mice. Chronic cotinine treatment improved learning and memory in aged animals, indicated by decreased latency time, and increased time spent in the target quadrant and discrimination index (DI) in the MWM and NOR tasks. Also, chronic cotinine injection increased total antioxidant capacity (TAC), SOD and GSH-px activity, PSD-95, GAP-43, SYN, brain-derived neurotrophic factor, and neural growth factor levels and decreased malondialdehyde, TNF-α, and IL-1β in the hippocampus of aged mice. Conversely, MLA treatment reversed most of the mentioned effects via the blockade of α7 nAChRs. Cotinine improves age-induced memory and learning impairment via its modulatory effects on α7 nAChRs and subsequent activation/deactivation of the mentioned pathways in the hippocampus of aged mice.


Recurrent primary acquired melanosis with atypia involving a clear corneal phacoemulsification wound.
To report a case of corneal primary acquired melanosis (PAM) with atypia after cataract surgery. Retrospective case report with literature review. Excision of an elevated pigmented conjunctival lesion was performed at the time of cataract extraction by clear corneal phacoemulsification by an outside surgeon. Histopathologic examination revealed PAM with atypia. Three months after the initial surgery, recurrent melanosis involving the peripheral corneal epithelium was noted, with extension of pigment into the corneal stroma through the paracentesis site. Excision of the involved corneal epithelium and the adjacent conjunctiva was performed, and microscopically recurrent PAM with atypia was confirmed. Adjuvant cryotherapy was applied at the time of surgery, and topical mitomycin C was given postoperatively. Repeat biopsies revealed no remaining malignancy, and the intrastromal pigment has disappeared during 18 months of follow-up. We present this case to illustrate the importance of complete evaluation and treatment of potentially atypical melanocytic conjunctival lesions before proceeding with elective intraocular surgery.


Outbreak of severe diarrhea due to zoonotic Cryptosporidium parvum and C. xiaoi in goat kids in Chungcheongbuk-do, Korea.
Severe diarrhea was reported in goat kids in Chungcheongbuk-do, Korea, from 2021 to 2023, and Cryptosporidium infection was suspected. To confirm the cause of this outbreak, fecal samples were collected from goat farms where diarrhea had been reported and analyzed for Cryptosporidium infection using a molecular assay. A total of 65 fecal samples, including 37 from goats with diarrhea and 28 from goats without diarrhea, were collected from six goat farms. Forty-eight of the goats were kids (<2 months) and 17 were adults (>1 year). Cryptosporidium was identified in 53.8% (35/65) of total samples. Overall, 86.5% (32/37) of the diarrheic fecal samples tested positive; however, Cryptosporidium was not detected in any fecal sample from non-diarrheic adult goats. Therefore, cryptosporidiosis was significantly associated with diarrhea in goat kids, and adult goats were not responsible for transmission of Cryptosporidium to them. Phylogenetic analysis and molecular characterization revealed two Cryptosporidium species, namely, C. parvum (n = 28) and C. xiaoi (n = 7). In the C. parvum-positive samples, gp60 gene analysis revealed three zoonotic subtypes-IIaA18G3R1, IIdA15G1, and IIdA16G1. To the best of our knowledge, this study is the first to identify C. parvum IIaA18G3R1 and IIdA16G1 in goats, as well as the first to identify C. xiaoi in goats in Korea. These results suggest that goat kids play an important role as reservoir hosts for different Cryptosporidium species and that continuous monitoring with biosecurity measures is necessary to control cryptosporidiosis outbreaks.


A further investigation of category learning by inference.
Categories are learned in many ways besides by classification, for example, by making inferences about classified items. One hypothesis is that classifications lead to the learning of features that distinguish categories, whereas inferences promote the learning of the internal structure of categories, such as the typical features. Experiment 1 included single-feature and full-feature classification tests following either classification or inference learning. Consistent with predictions, inference learners did better on the single tests but worse on the full tests. Experiment 2 further showed that inference learners, unlike classification learners, were no better at classifying items that they had seen at study compared with equally typical items they had not seen at study. Experiment 3 showed that features queried about during inference learning were classified better than ones not queried about, although even the latter features showed some learning on single-feature tests. The discussion focuses on how different types of category learning lead to different category representations.


Text4baby in the United States and Russia: an opportunity for understanding how mHealth affects maternal and child health.
Text4baby uses new technology to deliver health messages and engage pregnant women and new mothers in healthy behaviors. The authors describe the need for carefully conducted early adopter epidemiologic evaluation and describe one such evaluation in a women, infant, and children clinic population in the United States and its proposed adaptation for use among early users of Text4baby in Russia. Collaborative efforts among countries can guide international understanding and use of best practices of this emerging technology.


Physio-biochemical and transcriptomic analysis reveals that the mechanism of Bacillus cereus G2 alleviated oxidative stress of salt-stressed Glycyrrhiza uralensis Fisch. seedlings.
Salt stress severely affects the growth and productivity of Glycyrrhiza uralensis. Our previous research found that the endophyte Bacillus cereus G2 alleviated the osmotic and oxidative stress in G. uralensis exposed to salinity. However, the mechanism is still unclear. Here, a pot experiment was conducted to analyse the change in parameters related to osmotic adjustment and antioxidant metabolism by G2 in salt-stressed G. uralensis at the physio-biochemistry and transcriptome levels. The results showed that G2 significantly increased proline content by 48 %, glycine betaine content by 75 % due to activated expression of BADH1, and soluble sugar content by 77 % due to upregulated expression of α-glucosidase and SS, which might help to decrease the cell osmotic potential, enable the cell to absorb water, and stabilize the cell's protein and membrane structure, thereby alleviating osmotic stress. Regarding antioxidant metabolism, G2 significantly decreased malondialdehyde (MDA) content by 27 %, which might be ascribed to the increase in superoxide dismutase (SOD) activity that facilitated the decrease in the superoxide radical (O2‾) production rate; it also increased the activities of catalase (CAT), ascorbate peroxidase (APX) and glutathione peroxidase (GPX), which helped stabilize the normal level of hydrogen peroxide (H2O2). G2 also increased glutathione (GSH) content by 65 % due to increased glutathione reductase (GR) activity and GSH/GSSG ratio, but G2 decreased oxidized glutathione (GSSG) content by 13 % due to decreased activity of dehydroascorbate reductase (DHAR), which could provide sufficient substrates for the ascorbate-glutathione (AsA-GSH) cycle to eliminate excess H2O2 that was not cleared in a timely manner by the antioxidant enzyme system. Taken together, G2 alleviated osmotic stress by increasing proline, soluble sugar, and glycine betaine contents and alleviated oxidative stress by the synergistic effect of antioxidant enzymes and the AsA-GSH cycle. Therefore, the results may be useful for explaining the mechanism by which endophyte inoculation regulates the salt tolerance of crops.


[Anesthesia during pregnancy].
The need for general or regional anesthesia due to nonobstetric surgery occurs in up to 2% of all pregnancies. Safe perioperative care is a challenge to anesthetists. Profound knowledge of physiological and pathophysiological changes during pregnancy and the possible influence of different drugs and anesthesia techniques on mother and fetus is necessary. Although data from randomized controlled trials is missing, safe anesthesia during pregnancy is well documented for nearly every operative procedure. Interdisciplinary cooperation between surgeon, obstetrician, neonatologist, and anesthetist is the key to optimal patient care.


Vascular plexiform leiomyoma mimicking uterine tumor resembling ovarian sex cord tumor.
Leiomyomata are common benign smooth muscle neoplasms with a usually easily recognizable histologic pattern. However, there is a wide variety of subtypes described in the literature, characterized by predominance of a particular distinct histologic pattern. Here we describe a case of a highly vascular leiomyoma with a prominent plexiform pattern and cords and tubules of epithelioid cells that mimics a uterine tumor resembling an ovarian sex cord tumor.


Median nerve conduction studies in rabbits.
When planning nerve conduction studies using animal models, the sciatic nerve is often used and the upper extremity nerves are not preferred due to the size of laboratory animals. This study aimed to present the method and mean values of median nerve conduction studies in laboratory rabbits. Fifty-five six-month-old male New Zealand white rabbits weighing 2 to 2.5 kg were included in nerve conduction studies performed under anesthesia. The compound muscle action potential amplitude and distal latency values were recorded for the median motor nerve with the electrodes placed on the flexor digitorum superficialis muscle and tendon. A total of 110 median nerves were evaluated. The mean amplitude of the median nerve was 30.6 ± 6.8, mV the median nerve distal latency was 1.3 ± 0.2 ms, and the mean intensity of stimulation inducing a response was 2.5 ± 1 mA. The mean values obtained by the median motor nerve conduction method in this study can act as a guide for future nerve interventions undertaken in the upper extremities.


[Self-relaxation techniques for glaucoma patients. Significance of autogenic training, hypnosis and music therapy].
Glaucoma is currently the second most common cause of severe visual impairment and blindness worldwide. Standard pharmaceutical and surgical interventions often fail to prevent progression of glaucomatous optic neuropathy. To evaluate whether adjuvantly applied self-relaxation techniques can significantly impact intraocular pressure, ocular perfusion and the overall mental state of affected patients. A search of the literature was carried out and a comprehensive overview of currently available data is presented. Autogenic training, hypnosis and music therapy can significantly impact intraocular pressure, ocular perfusion and overall mental state of patients suffering from glaucoma. As all of these adjuvant therapeutic options are cost-effective, available almost everywhere and at anytime as well as without any known side effects, they can be useful additional techniques in the overall concept for treating glaucoma patients. Regular ocular examinations by an ophthalmologist are, however, mandatory.


The effect of short-and long-term corticosteroid treatment on sleep-associated growth hormone secretion.
Eight healthy medical studients and four renal transplant patients had blood sampled two or three times hourly throughout EEG monitored nocturnal sleep. This was carried out on the healthy subjects for a total of 12 nights without medication (control nights asleep), a total of 12 nights following 40 mg of flucortolone the previous morning, and a total of 6 nights with similar blood sampling when sleep was prevented (control nights awake). Four renal transplant patients who were receiving long-term therapy with prednisolone were similarly studied (total of 7 nights asleep). Circulating corticosteroid and growth hormone (GH) levels were determined. A peak of GH was seen during the first 2 h of sleep on the control nights when slow-wave sleep predominated. The GH peak was absent on the control nights awake. The pattern of plasma corticosteroid levels was identical during control nights asleep and awake. Both single-dose and chronic corticosteroid administration inhibited the GH peak associated with slow-wave sleep. Chronic corticosteroid therapy, but no single-dose administration in the morning, suppressed the circadian rise of plasma corticosteroids which normally occurs late in sleep.


Nanocellulose composites with enhanced interfacial compatibility and mechanical properties using a hybrid-toughened epoxy matrix.
Although there is a growing interest in utilizing nanocellulose fibres (NCFs) based composites for achieving a higher sustainability, mechanical performance of these composites is limited due to the poor compatibility between fibre reinforcement and polymer matrices. Here we developed a bio-nanocomposite with an enhanced fibre/resin interface using a hybrid-toughened epoxy. A strong reinforcing effect of NCFs was achieved, demonstrating an increase up to 88% in tensile strength and 298% in tensile modulus as compared to neat petro-based P-epoxy. The toughness of neat P-epoxy was improved by 84% with the addition of 10wt% bio-based E-epoxy monomers, which also mitigated the amount of usage of bisphenol A (BPA). The morphological analyses showed that the hybrid epoxy improved the resin penetration and fibre distribution significantly in the resulting composites. Thus, our findings demonstrated the promise of developing sustainable and high performance epoxy composites combing NCFs with a hybrid petro-based and bio-based epoxy resin system.


A Wingless and Notch double-repression mechanism regulates G1-S transition in the Drosophila wing.
The control of tissue growth and patterning is orchestrated in various multicellular tissues by the coordinated activity of the signalling molecules Wnt/Wingless (Wg) and Notch, and mutations in these pathways can cause cancer. The role of these molecules in the control of cell proliferation and the crosstalk between their corresponding pathways remain poorly understood. Crosstalk between Notch and Wg has been proposed to organize pattern and growth in the Drosophila wing primordium. Here we report that Wg and Notch act in a surprisingly linear pathway to control G1-S progression. We present evidence that these molecules exert their function by regulating the expression of the dmyc proto-oncogene and the bantam micro-RNA, which positively modulated the activity of the E2F transcription factor. Our results demonstrate that Notch acts in this cellular context as a repressor of cell-cycle progression and Wg has a permissive role in alleviating Notch-mediated repression of G1-S progression in wing cells.


Superiority of bridging techniques with medial fixation on initial strength.
The purpose of our study was to evaluate the initial fixation strength of bridging techniques compared to other suture techniques for rotator cuff repair using a biomechanical animal model, which incorporated pretesting of intact tendons. Seventy-six fresh bovine shoulders were used for testing seven suture configurations including simple suture (SS), mattress suture (MS), Mason-Allen (MA), modified double row (mDR), SpeedBridge (SpB), SpeedBridge with medial fixation (mSpB), and double-mattress SutureBridge (dmSuB) techniques. Cyclic loading was performed with all intact bone-tendon complex before (pretest) and after repair of the tendon (main test) at the level of 10 and 180 N at 100 Hz with displacement-controlled ramps of ± 33 mm/s. The pretest was stopped after 200 cycles. For the main test, the loading scheme was continued for a maximum of 500 cycles or until failure. The mean elongation of all 76 intact tendons measured at the pretest was 3.8 ± 0.6 mm (2.4-5.4 mm). No differences of gap formations at the 1st cycle were detected between SS, MS, MA, and mDR. SpB showed significant higher gap formations compared to all other suture techniques (p = 0.001). No significant differences were detected between mSpB and dmSuB, whereas both techniques were significant different when compared to the other groups (p < 0.05). In this study, results showed that bridging techniques with medial fixations have superior initial repair strength compared to other suture techniques. Knowledge of initial fixation strength of rotator cuff repair techniques may be of informative value to the surgeon.


[Anti-rabies vaccination. Comparative analysis of the responses of Flury Hep, Fuenzalida, and inactivated Flury Hep vaccines].
The authors verified the following: The FLURY HEP vaccine, with modified virus, confers a higher level of protection when applied by intracerebral route in laboratory animals. With an equal number of viral particles of FLURY HEP modified virus and fixed virus (FUENZALIDA type vaccine), inoculated intracerebrally and intramusculary, a better protection was obtained with the first kind of vaccine, specially by intracerebral route. These conditions suggest the possibility of replication of modified HEP virus in the cells of the central nervous system. The results show that the concentration of neutralizing antibodies in the serum is not the only responsable for protection, but suggests the possibility of factors or of cellular immunity acting in the animal's protection against rabies.


Multiple histone deacetylases are recruited by corepressor Sin3 and contribute to gene repression mediated by Opi1 regulator of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae.
Yeast genes of phospholipid biosynthesis are negatively regulated by repressor protein Opi1 when precursor molecules inositol and choline (IC) are available. Opi1-triggered gene repression is mediated by recruitment of the Sin3 corepressor complex. In this study, we systematically investigated the regulatory contribution of subunits of Sin3 complexes and identified Pho23 as important for IC-dependent gene repression. Two non-overlapping regions within Pho23 mediate its direct interaction with Sin3. Previous work has shown that Sin3 recruits the histone deacetylase (HDAC) Rpd3 to execute gene repression. While deletion of SIN3 strongly alleviates gene repression by IC, an rpd3 null mutant shows almost normal regulation. We thus hypothesized that various HDACs may contribute to Sin3-mediated repression of IC-regulated genes. Indeed, a triple mutant lacking HDACs, Rpd3, Hda1 and Hos1, could phenocopy a sin3 single mutant. We show that these proteins are able to contact Sin3 in vitro and in vivo and mapped three distinct HDAC interaction domains, designated HID1, HID2 and HID3. HID3, which is identical to the previously described structural motif PAH4 (paired amphipathic helix), can bind all HDACs tested. Chromatin immunoprecipitation studies finally confirmed that Hda1 and Hos1 are recruited to promoters of phospholipid biosynthetic genes INO1 and CHO2.


Circulating immune complexes in asbestos workers.
Circulating immune complexes, rheumatoid factor, and antinuclear antibodies were evaluated in 25 asbestos insulation workers and 32 brick mason controls. There were 10 asbestos workers with radiographic parenchymal or pleural changes, consistent with their asbestos exposure. There were no differences in antinuclear antibodies or rheumatoid factor between asbestos workers and controls. The asbestos workers had significantly increased levels of IgG and IgA circulating immune complexes. There was a significant correlation between IgA circulating immune complexes and radiographic changes.


Hypothesis: the mitochondrial NO(*) signaling pathway, and the transduction of nitrosative to oxidative cell signals: an alternative function for cytochrome C oxidase.
Nitric oxide (NO(*)) signaling is diverse, and involves reaction with free radicals, metalloproteins, and specific protein amino acid residues. Prominent among these interactions are the heme protein soluble guanylate cyclase and cysteine residues within several proteins such as caspases, the executors of apoptosis. Another well characterized site of NO(*) binding is the terminal complex of the mitochondrial respiratory chain, cytochrome c oxidase, although the downstream signaling effects of this interaction remain unclear. Recently, it has been recognized that the intracellular formation of hydrogen peroxide (H(2)O(2)) by controlled mechanisms contributes to what we term "redox tone," and so controls the activity and activation thresholds of redox-sensitive signaling pathways. In this hypothesis paper, it is proposed that NO(*)-dependent modulation of the respiratory chain can control the mitochondrial generation of H(2)O(2) for cell signaling purposes without affecting ATP synthesis.


Relationship of the electrocardiographic response to exercise to geometric and functional findings in aortic regurgitation.
The exercise ECGs of 30 patients with pure aortic regurgitation (AR) were compared with functional and geometric variables measured by echocardiography and radionuclide cineangiography. The 10 patients with positive ECG responses to exercise (greater than or equal to 0.1 mV additional downsloping or horizontal ST segment depression) were similar to the 20 patients with negative tests with respect to mean age, exercise duration, peak work load achieved, symptoms, and resting ECG findings. Patients with positive exercise tests had significantly reduced left ventricular (LV) ejection fractions at rest (44 +/- 4% vs 52 +/- 2%) and during peak exercise (38 +/- 3% vs 48 +/- 2%), lower fractional shortening at rest (27 +/- 1% vs 34 +/- 2%), higher end-systolic wall stress (150 +/- 18 vs 99 +/- 8 dynes/cm2 X 10(3], lower left ventricular relative wall thickness (0.26 +/- 0.01 vs 0.30 +/- 0.01), and greater end-systolic diameter (5.7 +/- 0.3 vs 4.5 +/- 0.2 cm) than patients with negative tests (p less than 0.05 for all comparisons). Among the 18 asymptomatic patients, positive tests were associated with lower resting fractional shortening, lower exercise ejection fraction, higher wall stress, and greater end-systolic diameter. These data demonstrate that a positive exercise ECG in aortic regurgitation identifies patients, even when asymptomatic, who have developed markedly abnormal left ventricular functional and geometric responses to volume load, while a negative exercise ECG identifies a subset of asymptomatic patients who are unlikely to have severe ventricular dysfunction.


One-year changes in self-reported napping behaviors across the retirement transition.
To estimate associations of retirement with self-reported frequency and duration of naps. Prospective cohort study. Population-based. 1359 current and former Wisconsin state employees, aged 54-69. Four annual surveys mailed between 2010 and 2014 elicited employment status and nap characteristics. Changes in employment status and nap characteristics were identified from survey pairs measured 1 year apart (up to 3 survey pairs per subject). General linear mixed models with repeated measures were used to estimate changes in minutes napped per week (MNPW), weekly nap frequency, and individual nap duration as predicted by retirement transitions vs stable employment status. All models were adjusted for demographic characteristics, self-rated health, medical diagnoses, sleep problems, circadian preference, and change in nocturnal sleep duration. There were 3101 survey pairs in the analytic sample. Full retirement (transition from working ≥35 h/wk to not working for pay) over a 1-year period predicted a statistically significantly larger mean change in MNPW than stable employment status: mean (95% confidence interval) = +48 (+16, +80) MNPW. Associations between staged retirement transitions (from full-time to part-time work, or from part-time work to full retirement) and 1-year changes in MNPW were not statistically significant. The MNPW changes associated with full retirement were attributable to nap frequency increase of +0.4 (+0.1, +0.8) d/wk; nap duration did not change significantly. Compared with stable employment status, full retirement is associated with an average 1-year increase of +48 MNPW. This change is attributable to a frequency gain of 0.4 d/wk napped. Changes in nap duration were negligible.


Dapiglutide, a novel dual GLP-1 and GLP-2 receptor agonist, attenuates intestinal insufficiency in a murine model of short bowel.
Extensive intestinal resection may lead to short bowel (SB) syndrome, resulting in intestinal insufficiency or intestinal failure (IF). Intestinal insufficiency and IF involve deficiency of the proglucagon-derived hormones glucagon-like peptide-1 (GLP-1) and GLP-2. Two major problems of SB are epithelial surface loss and accelerated transit. Standard treatment now targets intestinal adaptation with a GLP-2 analogue to enlarge absorptive surface area. It is possible that additional benefit can be gained from a combination of GLP-1 and GLP-2 activity, with the aim to enlarge intestinal surface area and slow intestinal transit. The GLP-1- and GLP-2-specific effects of the novel dual GLP-1 receptor (GLP-1R) and GLP-2 receptor (GLP-2R) agonist dapiglutide (rINN) were characterized in rodents. Furthermore, in a murine SB model of intestinal insufficiency with 40% ileocecal resection, the influence of dapiglutide on intestinal growth, body weight, food intake, volume status, and stool water content was tested against vehicle and sham-operated male mice. Dapiglutide significantly improves oral glucose tolerance, reduces intestinal transit time, and promotes intestinal growth. In the SB mouse model, dapiglutide promotes body weight recovery, despite unchanged intake of liquid diet. Dapiglutide promotes significant intestinal growth, as indicated by significantly increased villus height as well as intestinal length. Furthermore, dapiglutide reduces stool water losses, resulting in reduced plasma aldosterone. Dapiglutide possesses specific and potent GLP-1R and GLP-2R agonist effects in rodents. In the murine SB model, combined unimolecular GLP-1R and GLP-2R stimulation with dapiglutide potently attenuates intestinal insufficiency and potentially also IF.


Fast algorithm of phase masks for image encryption in the Fresnel domain.
A high performance lensless optical security system based on the discrete Fresnel transform is presented. Two phase-only masks are generated with what we believe to be a novel and efficient algorithm. Their position coordinates and the wavelength are used as encoding parameters in the encryption process. Compared with previous studies, the main advantage of this proposed encryption system is that it does not need any iterative algorithms to produce the masks, and that makes it very efficient and easy to implement without losing the encryption security.


[Psychiatric and Somatic Comorbidities of Eating Disorders and Obesity in Female Adolescent and Adult Inpatients].
Objective The main aim of this study was to determine the prevalence of somatic and psychiatric comorbidities in female inpatients diagnosed with an eating disorder or obesity. Methods Statutory health insurance data (11 - 25 years, N = 1269) was analysed. Results The most frequent comorbidities for both groups were affective, neurotic, stress-related and somatoform as well as personality disorders and diseases of the digestive system. Conclusion Close to half of the patients diagnosed with an eating disorder suffered from psychiatric comorbidities. The majority of obese patients were diagnosed with somatic comorbidities.


Direct capture and amplification of nucleic acids using a universal, elution-free magnetic bead-based method for rapid pathogen detection in multiple types of biological samples.
Nucleic acid amplification tests (NAATs) have become an attractive approach for pathogen detection, and obtaining high-quality nucleic acid extracts from biological samples plays a critical role in ensuring accurate NAATs. In this work, we established an elution-free magnetic bead (MB)-based method by introducing polyethylene-polypropylene glycol (PEPPG) F68 in lysis buffer and using NaOH solution instead of alcohols as the washing buffer for rapid nucleic acid extraction from multiple types of biological samples, including nasopharyngeal swabs, serum, milk, and pork, which bypassed the nucleic acid elution step and allowed the nucleic acid/MB composite to be directly used as the template for amplification reactions. The entire extraction process was able to be completed in approximately 7 min. Even though the nucleic acid/MB composite could not be used for quantitative real-time PCR (qPCR) assays, this elution-free MB-based method significantly improved the sensitivity of the loop-mediated isothermal amplification (LAMP) assay. The sensitivity of the quantitative real-time LAMP (qLAMP) assays combined with this elution-free MB-based method showed an improvement of one to three orders of magnitude compared with qLAMP or qPCR assays combined with the traditional MB-based method. In addition to manual operation, like the traditional MB-based method, this universal, rapid, and facile nucleic acid extraction method also has potential for integration into automated robotic processing, making it particularly suitable for the establishment of an analysis platform for ultrafast and sensitive pathogen detection in various biological samples both in centralized laboratories and at remote sites.


The journey of toluene to complete mineralization via heat-activated peroxydisulfate in water: intermediates analyses, CO2 monitoring, and carbon mass balance.
Our study has thoroughly investigated the complete mineralization of toluene in water via heat-activated peroxydisulfate (PDS) by: (1) monitoring concentrations/peak areas of various intermediates and CO2 throughout the reaction period and (2) identifying water-soluble and methanol-soluble intermediates, including trimers, dimers, and organo-sulfur compounds, via non-target screening using high-resolution mass spectrometry. Increased temperature and PDS dosage enhanced toluene removal/mineralization kinetics and increased the rate/extent of benzaldehyde formation and its further transformation. Artificial groundwater and phosphate buffer minimally impacted toluene removal but significantly decreased benzaldehyde formation, indicating a shift in transformation pathways. The stoichiometric PDS dose (18 mM at 40 °C) was adequate to completely mineralize toluene (1 mM), with < 10% PDS needed to transform toluene to intermediates. Toluene transformation to intermediates occurred in 47 h (kobs,toluene = 0.594 h-1) whereas 564 h were required for complete mineralization (kobs,CO2 = 0.0038 h-1). O2 accumulated once mineralization neared completion. A carbon mass balance, including quantification of nine intermediates and CO2 throughout the transformation period, showed that unquantified/unknown intermediates (including yellowish-white precipitates) reached as high as 80% of total carbon before transformation to CO2. Possible toluene transformation pathways via hydroxylation, sulfate addition, and oxidative coupling are proposed.


A practical guide to using the World Federation for Medical Education standards. WFME 2: educational program.
Preparing a medical school for institutional review of all aspects of the school's programs requires an understanding of the international standards being used and adequate preparation and planning (MacCarrick et al. in Med Teach 32(5):e227, 2010; MacCarrick in Ir J Med Sci, 2010). This series examines each of the nine standards developed by the World Federation for Medical Education (WFME) (World Federation for Medical Education in Basic medical education WFME global standards for quality improvement, WFME Office, University of Copenhagen, Denmark, 2003) with practical advice on their use in both self-review and independent accreditation processes. The WFME standard 2 (Educational Program) examines in detail the program offered by the medical school, the instructional methods used to deliver the program, how the program is managed and how the program is linked with subsequent stages of the medical education continuum. Evidence of a strong nexus between the research activities of the medical school and the school's teaching mission is vital. Accrediting teams will examine carefully the school's resource allocation model and seek evidence of effective consultation by the school's central curriculum committee.


Engineered citrate synthase alters Acetate Accumulation in Escherichia coli.
Metabolic engineering is used to improve titers, yields and generation rates for biochemical products in host microbes such as Escherichia coli. A wide range of biochemicals are derived from the central carbon metabolite acetyl-CoA, and the largest native drain of acetyl-CoA in most microbes including E. coli is entry into the tricarboxylic acid (TCA) cycle via citrate synthase (coded by the gltA gene). Since the pathway to any biochemical derived from acetyl-CoA must ultimately compete with citrate synthase, a reduction in citrate synthase activity should facilitate the increased formation of products derived from acetyl-CoA. To test this hypothesis, we integrated into E. coli C ΔpoxB twenty-eight citrate synthase variants having specific point mutations that were anticipated to reduce citrate synthase activity. These variants were assessed in shake flasks for growth and the production of acetate, a model product derived from acetyl-CoA. Mutations in citrate synthase at residues W260, A267 and V361 resulted in the greatest acetate yields (approximately 0.24 g/g glucose) compared to the native citrate synthase (0.05 g/g). These variants were further examined in controlled batch and continuous processes. The results provide important insights on improving the production of compounds derived from acetyl-CoA.


Theory-based research in schizophrenia.
Theoretical models to guide research into schizophrenia. To review the most commonly used biological and environmental models of schizophrenia. Published literature and research conducted by the author. The vulnerability model includes both biological and environmental variables that impact the course of schizophrenia and treatment. Thus, it may be a useful framework for nursing research examining responses to various psychosocial treatments in schizophrenia.


Condensed tannins act as anthelmintics by increasing the rigidity of the nematode cuticle.
Tannins and tanniferous plant extracts have been discussed as sustainable means for helminth control in the past two decades in response to a dramatic increase of resistances towards standard anthelmintics. While their bioactivities have been broadly investigated in vitro and in vivo, less is known about their mode of action in nematodes, apart from their protein binding properties. In the current study we therefore investigated the impact of a phytochemically well characterized plant extract from Combretum mucronatum, known to contain procyanidins as the active compounds, on the model organism Caenorhabditis elegans. By different microscopic techniques, the cuticle was identified as the main binding site for tannins, whereas underlying tissues did not seem to be affected. In addition to disruptions of the cuticle structure, molting defects occurred at all larval stages. Finally, an increased rigidity of the nematodes' cuticle due to binding of tannins was confirmed by force spectroscopic measurements. This could be a key finding to explain several anthelmintic activities reported for tannins, especially impairment of molting or exsheathment as well as locomotion.


Racial differences in opioid withdrawal syndrome among neonates with intrauterine opioid exposure.
The aim of this study was to investigate the association between race and severe neonatal opioid withdrawal syndrome (NOWS) in infants exposed to intrauterine opioids. This is a prospective observational study on intrauterine opioid-exposed term infants. Exposure to opioids was based on maternal disclosure, urine, or umbilical cord drug screening. Severe NOWS was defined based on modified Finnegan scoring and the need for pharmacological intervention. One hundred and fifty mother-infant pairs, 60 Black and 90 White with history of opioid exposure during pregnancy, were included. More White than Black infants developed NOWS that required pharmacological treatment, 70 vs. 40%: RR = 1.75 (1.25-2.45). In adjusted analysis, there was no significant association between race and the development of severe NOWS in mothers who attended opioid maintenance treatment program (OMTP). However, in mothers who did not attend OMTP, White race remained a significant factor associated with the development of severe NAS, RR = 1.69 (1.06, 2.69). Severe NOWS that required pharmacological intervention was significantly higher in White than in Black infants born to mothers who did not attend OMTP. Larger studies are needed to evaluate the association between social as well as genetic factors and the development of NOWS. There is a significant association between race and development of severe NOWS.


The sphingosine 1-phosphate receptor agonist FTY720 interfered the distribution of dendritic cell and induced the maternal-fetal immune tolerance.
The aim of this study was to investigate the effect of FTY720, an agonist of the sphingosine 1-phosphate (S1P) receptor, on the embryo loss rate in mice of spontaneous abortion model and the underlying mechanism. The effect of intraperitoneal injection of FTY720 on the embryo loss rate in mice of spontaneous abortion model was observed. The expression of S1PR on the dendritic cell (DC) surface was detected by reverse transcription polymerase chain reaction. The quantity and maturation of DCs in peripheral blood and local tissues of pregnant mice, and the expression of CCL19 as well as its receptor C-C chemokine receptor 7 (CCR7) were detected by flow cytometry and immunohistochemistry. Chemotaxis assay was performed to verify the effect of FTY720 on the chemotaxis of DCs. (1) FTY720 had no significant effect on the embryo loss rate in normal pregnant rats. In contrast, adoptive transferring of FTY720 significantly reduced the embryo loss rate of the spontaneous abortion mouse model (P < 0.05). (2) S1PR was extensively expressed on DC surface. The S1P receptor agonist FTY720 reduced the expressions of DC surface chemokines and its receptor (P < 0.05), resulting in a significant reduction in the number of DCs that were chemoattracted to maternal-fetal interface flow cytometry (P < 0.05). (3) FTY720 had no significant effect on the differentiation and apoptosis rate of DCs (P > 0.05). We hypothesized that FTY720 may reduce the number of DCs that were chemoattracted to the maternal-fetal interface by downregulating the expression of CCR7, which ultimately induces maternal-fetal immune tolerance.


Preventing neuronal damage and inflammation in vivo during cortical microelectrode implantation through the use of poloxamer P-188.
The aim of this study was to test the efficacy of Poloxamer P188 to reduce cell death and immune response associated with mechanical trauma to cells during implantation of a chronic recording electrode. Ceramic multi-site recording electrodes were implanted bilaterally into 15 adult male Long-Evans rats. One of each pair was randomly assigned to receive a coating of Poloxamer while the other was treated with saline. The extent of neuron loss, and glial cell recruitment were characterized at 2, 4 and 6 weeks post-implantation by stereologic analysis. At 2 and 4 weeks post-implantation, Poloxamer-coated implants showed significantly fewer glial cells and more neurons in the peri-electrode space than controls; however, this significance was lost by 6 weeks. These findings are the first to suggest that Poloxamer has neuroprotective effects in vivo; however, at a fixed loading dose, these effects are limited to approximately 1 month post-implantation.


A virtual reality intervention (Second Life) to improve weight maintenance: Rationale and design for an 18-month randomized trial.
Despite the plethora of weight loss programs available in the US, the prevalence of overweight and obesity (BMI≥25kg/m(2)) among US adults continues to rise at least, in part, due to the high probability of weight regain following weight loss. Thus, the development and evaluation of novel interventions designed to improve weight maintenance are clearly needed. Virtual reality environments offer a promising platform for delivering weight maintenance interventions as they provide rapid feedback, learner experimentation, real-time personalized task selection and exploration. Utilizing virtual reality during weight maintenance allows individuals to engage in repeated experiential learning, practice skills, and participate in real-life scenarios without real-life repercussions, which may diminish weight regain. We will conduct an 18-month effectiveness trial (6 months weight loss, 12 months weight maintenance) in 202 overweight/obese adults (BMI 25-44.9kg/m(2)). Participants who achieve ≥5% weight loss following a 6month weight loss intervention delivered by phone conference call will be randomized to weight maintenance interventions delivered by conference call or conducted in a virtual environment (Second Life®). The primary aim of the study is to compare weight change during maintenance between the phone conference call and virtual groups. Secondarily, potential mediators of weight change including energy and macronutrient intake, physical activity, consumption of fruits and vegetables, self-efficacy for both physical activity and diet, and attendance and completion of experiential learning assignments will also be assessed.


On the status of β-cell dysfunction and insulin resistance of breast cancer patient without history of diabetes after systemic treatment.
To estimate the status of β-cell dysfunction and insulin resistance of breast cancer (BC) patient without history of diabetes mellitus (DM) after systemic treatment through an oral glucose tolerance test (OGTT) and insulin releasing test (IRT). All the 128 BC patients without history of DM after systemic treatment underwent OGTT and IRT test. Fasting and 2-h glucose levels were measured to confirm undiagnosed DM and prediabetes. Insulin sensitivity was estimated by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index and disposition index (IGI/HOMA-IR). Insulin secretion was estimated by the insulinogenic index (IGI) [Δ insulin/Δ glucose (30-0 min)]. Insulin concentrations during the OGTT and IRT at baseline were used to derive the patterns of insulin secretion curve (pattern 1, pattern 2, pattern 3, pattern 4 and pattern 5), which were used to estimate the risk of developing DM. Of 128 BC patients without history of DM after systemic treatment, there were 46 cases (35.9%) of NGT, 60 cases (46.9%) of prediabetes and 22 cases (17.2%) of DM. The BMI of prediabetes and DM were higher than NGT groups with statistical significance. After adjusted for BMI, IGI was significantly lower in DM group but not significantly different between NGT group and prediabetes group. HOMA-IR, Matsuda index and disposition index were significantly different in DM group compared with NGT group and prediabetes and also significantly different between NGT and prediabetes groups. The total rates of patterns 4 and 5 in NGT and prediabetes groups were 15.3% (10.9 and 4.4%) and 48.3% (31.6 and 16.7%), respectively. β-Cell dysfunction and insulin resistance may appear in BC patients after systemic treatment. BC patients have high risk in development of DM even in NGT and prediabetes groups confirmed by OGTT.


Evaluation of the effects of nano-TiO2 on bioactivity and mechanical properties of nano bioglass-P3HB composite scaffold for bone tissue engineering.
To emulate bone structure, porous composite scaffold with suitable mechanical properties should be designed. In this research the effects of nano-titania (nTiO2) on the bioactivity and mechanical properties of nano-bioglass-poly-3-hydroxybutyrate (nBG/P3HB)-composite scaffold were evaluated. First, nBG powder was prepared by melting method of pure raw materials at a temperature of 1400 °C and then the porous ceramic scaffold of nBG/nTiO2 with 30 wt% of nBG containing different weight ratios of nTiO2 (3, 6, and 9 wt% of nTiO2 with grain size of 35-37 nm) was prepared by using polyurethane sponge replication method. Then the scaffolds were coated with P3HB in order to increase the scaffold's mechanical properties. Mechanical strength and modulus of scaffolds were improved by adding nTiO2 to nBG scaffold and adding P3HB to nBG/nTiO2 composite scaffold. The results of the compressive strength and porosity tests showed that the best scaffold is 30 wt% of nBG with 6 wt% of nTiO2 composite scaffold immersed for 30 s in P3HB with 79.5-80 % of porosity in 200-600 μm, with a compressive strength of 0.15 MPa and a compressive modulus of 30 MPa, which is a good candidate for bone tissue engineering. To evaluate the bioactivity of the scaffold, the simulated body fluid (SBF) solution was used. The best scaffold with 30 wt% of nBG, 6 wt% of P3HB and 6 wt% of nTiO2 was immersed in SBF for 4 weeks at an incubation temperature of 37 °C. The bioactivity of the scaffolds was characterized by AAS, SEM, EDXA and XRD. The results of bioactivity showed that bone-like apatite layer formed well at scaffold surface and adding nTiO2 to nBG/P3HB composite scaffold helped increase the bioactivity rate.


Hormonal response to enteral feeding and the possible role of peptide YY in pathogenesis of enteral feeding-related diarrhoea.
Diarrhoea is a common complication of enteral feeding. Previous studies have demonstrated a secretion of water and electrolytes in the ascending colon during intragastric but not intraduodenal enteral feeding. The cause of this secretion is likely to be neurohumoral in origin. This study was designed to examine the hormonal responses to enteral feeding. In vivo segmental colonic perfusion studies were undertaken. Before and at hourly intervals during these studies serum was taken for estimations of neurotensin (NT), pancreatic glucagon (PG), peptide YY (PYY) and vasoactive intestinal polypeptide (VIP). During fasting there was a median ascending colonic absorption of water in all groups. During feeding there was a net secretion in the ascending colon in both gastric groups and in the high load duodenal group, but not in the low load duodenal group. During these studies the PYY levels remained unchanged from fasting in the low and high load gastric groups. In the low and high load duodenal groups the PYY levels increased. The NT levels increased only in the high load duodenal group. There were no other changes in NT or in PG or VIP levels either between fasting and feeding, or between the gastric and duodenal groups. PYY is known to stimulate intestinal absorption. The absence of a rise during intragastric feeding may be important in the underlying mechanisms of enteral feeding-induced colonic secretion and hence enteral feeding-related diarrhoea.


The nitric oxide donor molsidomine improves survival and reduces hepatocyte apoptosis in cholestasis and endotoxemia.
Cholestasis and endotoxemia have been demonstrated to cause hepatocyte apoptosis through caspase-mediated pathways. In vitro nitric oxide (NO) donors reduce hepatocyte apoptosis and caspase activation in several models. The nitric oxide donor molsidomine improves survival in an in vivo model of endotoxemia. We tested the effect of molsidomine on survival and hepatocyte apoptosis in a model of obstructive jaundice and endotoxemia. Sprague-Dawley rats underwent common bile duct ligation on day 1. On day 3, animals were given either 100 mg/kg of molsidomine or an equivalent volume of saline, and 30 minutes later they were given endotoxin 3 mg/kg or 10 mg/kg intravenously. Animals were sacrificed 4 or 16 hours after endotoxin injection. Serum samples were analyzed for alanine aminotransferase and frozen liver samples were analyzed for caspase 3 activity. Paraffin-embedded liver sections were assayed for apoptosis using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. Survival was measured in a separate experiment in which animals underwent the same protocol, but were given three different doses of endotoxin and were observed for 72 hours before sacrifice. At endotoxin 3 mg/kg, the 72-hour survival in saline-treated animals was 92%, which decreased to 45% at 10 mg/kg and to 29% at 15 mg/kg. All of the molsidomine-treated animals survived all endotoxin doses. Alanine aminotransferase was reduced in molsidomine-treated animals compared with those treated with saline. Apoptosis was attenuated in molsidomine-treated animals. Caspase 3 activity was decreased in molsidomine-treated animals compared with those given saline. Molsidomine attenuates caspase activation and hepatocyte apoptosis and improves survival after cholestatic endotoxic injury.


The role of the ZEB1-neuroinflammation axis in CNS disorders.
Zinc finger E-box binding homeobox 1 (ZEB1) is a master modulator of the epithelial-mesenchymal transition (EMT), a process whereby epithelial cells undergo a series of molecular changes and express certain characteristics of mesenchymal cells. ZEB1, in association with other EMT transcription factors, promotes neuroinflammation through changes in the production of inflammatory mediators, the morphology and function of immune cells, and multiple signaling pathways that mediate the inflammatory response. The ZEB1-neuroinflammation axis plays a pivotal role in the pathogenesis of different CNS disorders, such as brain tumors, multiple sclerosis, cerebrovascular diseases, and neuropathic pain, by promoting tumor cell proliferation and invasiveness, formation of the hostile inflammatory micromilieu surrounding neuronal tissues, dysfunction of microglia and astrocytes, impairment of angiogenesis, and dysfunction of the blood-brain barrier. Future studies are needed to elucidate whether the ZEB1-neuroinflammation axis could serve as a diagnostic, prognostic, and/or therapeutic target for CNS disorders.


Radio-iodobenzylguanidine for the scintigraphic location and therapy of adrenergic tumors.
Radioiodinated meta-iodobenzylguanidine, a recently developed radiopharmaceutical, has been shown to permit safe, noninvasive, sensitive, and specific scintigraphic location of pheochromocytomas of all types. The technique is especially efficacious in the case of extraadrenal primary lesions and locally recurrent and metastatic tumors. In addition to being taken up by pheochromocytomas, meta-iodobenzylguanidine may be used to image neuroblastomas, nonfunctioning paragangliomas, and carcinoid tumors. Lesions with high 131I-meta-iodobenzylguanidine uptake may respond to treatment with large doses of this radiopharmaceutical.


The mechanism of governments' and individuals' influence on protective behaviours during the second wave of COVID-19: a multiple mediation model.
Background: The SARS-CoV-2 virus continues to spread and resurge globally with signs of a second wave, despite actions by governments to curb the COVID-19 pandemic. However, evidence-based strategies to combat COVID-19 recurrence are poorly documented. Objective: To reveal how governments and individuals should act to effectively cope with future waves, this study proposed a preventive model of COVID-19 resurgence. Method: A questionnaire survey was conducted among 1,137 residents of Beijing, where the epidemic reoccurred. Structural equation model was used to explore the mechanism among government intervention, perceived efficacy, positive emotions, posttraumatic growth (PTG) and protective behaviours. Results: Data analysis revealed that during COVID-19 resurgence, government intervention could directly and indirectly influence protective behaviours through individual factors (i.e. perceived efficacy, positive emotions), and PTG could mediate the indirect pathway to protective behaviours. Conclusions: These findings implied that government intervention needs to be integrated with individual factors to effectively control repeated COVID-19 outbreaks.


Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1 deacetylase and induces T cell hyperactivation.
Symptoms of T cell hyperactivation shape the course and outcome of HIV-1 infection, but the mechanism(s) underlying this chronic immune activation are not well understood. We find that the viral transactivator Tat promotes hyperactivation of T cells by blocking the nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase SIRT1. Tat directly interacts with the deacetylase domain of SIRT1 and blocks the ability of SIRT1 to deacetylate lysine 310 in the p65 subunit of NF-kappaB. Because acetylated p65 is more active as a transcription factor, Tat hyperactivates the expression of NF-kappaB-responsive genes, a function lost in SIRT1-/- cells. These results support a model where the normal function of SIRT1 as a negative regulator of T cell activation is suppressed by Tat during HIV infection. These events likely contribute to the state of immune cell hyperactivation found in HIV-infected individuals.


Canine models of asthma and COPD.
Dogs have been extensively used to model the important components of asthma and COPD. Many of the key features of human asthma such as reversible airflow obstruction, pulmonary inflammation, airway hyperresponsiveness and cough are demonstrated in dogs after provocation with antigen, following a period of hyperventilation with dry air or after inhalation of ozone. Furthermore, standard anti-asthma drugs such as beta-adrenergic agonists, corticosteroids and leukotriene inhibitors are effective in these models. The pathology and pathophysiology of chronic bronchitis and emphysema can also be demonstrated in dogs after exposure to cigarette smoke, following inhalation of sulfur dioxide and by intra-tracheal or aerosol administration of proteolytic enzymes such as papain. These canine models of COPD have been used to evaluate a variety of new methodologies and treatments before they are tested in humans. This review highlights some of the important features of these canine models and how they have increased our understanding of the pathology, pathophysiology and control of human asthma and COPD.