Delayed endothelialization of watchman device identified with cardiac CT.
Left atrial appendage (LAA) closure with the Watchman device is increasingly used in patients with nonvalvular atrial fibrillation for stroke prevention. Though clinical trials have shown a similar combined risk of ischemic and hemorrhagic stroke, there is an increased risk of ischemic stroke in patients with a Watchman device compared with anticoagulation. Some ischemic strokes are related to a device-related thrombus (DRT), which may be attributable to delayed endothelialization of exposed fabric and metal. Patients undergoing Watchman LAA occlusion between January 2016 and June 2018 were enrolled in a prospective registry. From this cohort, 46 patients who had both transesophageal echocardiogram (TEE) and computed tomography (CT) at 45 days follow-up were selected for this study. The degree of LAA occlusion and type of leak were assessed by CT and TEE. TEE identified no patients with a significant (>5 mm) peri-device leak, 27 (58.6%) with nonsignificant peri-device leak (<5 mm), and 19 (41.4%) with complete occlusion. CT identified contrast in the LAA in 28 (60%) patients. However, in 10 (21.8%) of these patients, contrast entered the LAA through the fabric rather than around the device. No DRT were identified. These data reveal that the Watchman device remains porous 6 weeks after implantation in a substantial percentage of patients, suggesting delayed endothelialization of the device. Cardiac CT may help to differentiate between peri-device and trans-fabric leak. Additional studies are required to test whether prolonged anticoagulation in patients with trans-fabric leak may help to reduce the risk of DRT and ischemic stroke.


Intermittent pupillary capture of intraocular lens after transscleral fixation in congenital ectopia lentis patient triggered by dark environment: A case report.
Although transscleral-fixated intraocular lens (IOL) implantation has been the most frequently chosen treatment for patients with inadequate capsule support, the ghost pupillary capture phenomenon did not cause enough attention. We present an unusual case withintermittent pupillary capture of intraocular lens. After 5 minutes staying in the dark environment, the pentacam examination revealed a mild nasal pupillary capture of the IOL. A clear observation using the slit-lamp was attempted, and the light shining on the pupil sped up the sliding of the captured IOL. The captured portion of the IOL recovered rapidly accompanied with pupil retraction when the patient was exposed in the light. Pupillary capture of an IOL is an uncommon but potentially serious postoperative complication of transscleral fixation. Many pupillary capture cases may have been overlooked in the past. Physicians should be aware of its potential side effect, recognize its clinical manifestation, and knowledgeable of effective management.


Hip pain in patient with Crohn's disease. Occult retroperitoneal abscess as cause.
A 20-year-old man with Crohn's disease was seen as an outpatient for pain in the left hip and gait disturbance. Initially, arthritis of the hip was suspected, because of the absence of fever or abdominal abnormalities. Two weeks later, fever, malaise, and pneumaturia developed and urine culture grew Escherichia coli. Laparotomy revealed a large occult retroperitoneal abscess on the left side, which had been irritating the psoas muscle. Surgical drainage effected complete recovery of hip function. The abscess in this patient had a very unusual presentation and was diagnosed chiefly through a high index of suspicion after a careful physical examination.


Occurrence and pharmacological characterization of four human tachykinin NK2 receptor variants.
Tachykinin NK(2) receptor antagonists are potentially beneficial in treating various disorders including irritable bowel syndrome, urinary incontinence, depression and anxiety. The current study evaluates the frequency of single nucleotide polymorphisms (SNPs) in the human NK(2) receptor gene (TACR2). In addition, the potency of the endogenous peptide agonist neurokinin A (NKA), and the small molecule antagonists saredutant (NK(2)-selective) and ZD6021 (pan-NK antagonist) at the various NK(2) receptor protein variants were determined. The TACR2 gene was sequenced from 37 individuals. Two amino acid changing SNPs encoding the NK(2) receptor variants Ile23Thr and Arg375His were found. The frequency of the four possible protein variants differed between populations. Site-directed mutagenesis was performed introducing either SNP or both SNPs into the TACR2 gene and the constructs were transfected into CHO cells. NKA-evoked increases in intracellular Ca(2+) were monitored by FLIPR. The potency of saredutant and ZD6021 was evaluated by their ability to inhibit NKA-induced increases in intracellular Ca(2+). NKA evoked increases in intracellular Ca(2+) with a potency ranging between 1 and 5nM in CHO cells expressing the different constructs. Saredutant and ZD6021 blocked NKA-evoked increases in intracellular Ca(2+) with pK(b) values ranging between 8.8-9.3 and 7.9-8.7, respectively. The current study demonstrates that polymorphisms leading to the Ile23Thr and Arg375His amino acid exchanges are highly prevalent in the human TACR2 gene. These polymorphisms however do not appear to affect the potency of the endogenous agonist NKA or the small molecule antagonists saredutant and ZD6021 with respect to intracellular Ca(2+) signalling.


Nutriepigenomics and malnutrition.
Epigenetics is defined as the modulation of gene expression without changes to the underlying DNA sequence. Epigenetic alterations, as a consequence of in utero malnutrition, may play a role in susceptibility to develop adulthood diseases and inheritance. However, the mechanistic link between epigenetic modifications and abnormalities in nutrition remains elusive. This review provides an update on the association of suboptimal nutritional environment and the high propensity to produce adult-onset chronic illnesses with a particular focus on modifications in genome functions that occur without alterations to the DNA sequence. We will mention the drivers of the phenotype and pattern of epigenetic markers set down during the reprogramming along with novel preventative and therapeutic strategies. New knowledge of epigenetic alterations is opening a gate toward personalized medicine.


Conceptual and methodological issues in research on mindfulness and meditation.
Both basic science and clinical research on mindfulness, meditation, and related constructs have dramatically increased in recent years. However, interpretation of these research results has been challenging. The present article addresses unique conceptual and methodological problems posed by research in this area. Included among the key topics is the role of first-person experience and how it can be best studied, the challenges posed by intervention research designs in which true double-blinding is not possible, the nature of control and comparison conditions for research that includes mindfulness or other meditation-based interventions, issues in the adequate description of mindfulness and related trainings and interventions, the question of how mindfulness can be measured, questions regarding what can and cannot be inferred from self-report measures, and considerations regarding the structure of study design and data analyses. Most of these topics are germane to both basic and clinical research studies and have important bearing on the future scientific understanding of mindfulness and meditation.


Employment history indicators and mortality in a nested case-control study from the Spanish WORKing life social security (WORKss) cohort.
Employment has transitioned from stable to more flexible schemes. Little is known about the effects of dynamic working lives and mortality. We examined the association of employment, unemployment and inactivity on mortality among workers born in 1926-1988, in a nested case-control study of workers from the Spanish WORKss cohort. Cases were all deaths that occurred during 2004-2013 and controls were living persons, matched for sex and age at the time the case occurred. We had information on employment from 1981 to 2013. Logistic regression was used to measure the associations between the 3 employment history indicators separately by sex. There were 53,989 cases and an equal number of controls (n = 107,978). More than 16 years employed showed a protective effect against mortality in women (OR = 0.88, 95%CI: 0.81, 0.94) and men (OR = 0.76, 95%CI: 0.70, 0.79). The number of spells and time in unemployment and inactivity were significantly related to mortality in men, but not women. Sensitivity analyses by labor relationship showed stronger associations of unemployment (OR = 1.42, 95%CI: 1.13, 1.78) and inactivity (OR = 1.34; 95%CI: 1.09, 1.65) for temporary workers. Employment gaps are detrimental to health and have worse effects if the gaps occur without unemployment benefits or after temporary contracts. These results may drive improvement of labor and social policies that protect workers against the potential negative effects of dynamic work lives.


A Multi-Criteria Approach for Comparison of Ginger Extract and Conventional Irrigants in Root Canal Treatment.
Background Considering the importance of irrigation in dental root canal treatment, there is an urgent need to find a risk-free bioactive and antibacterial endodontic solution. Enterococcus faecalis, an anaerobic gram-positive coccus, has been identified as the main reason for endodontic infections. Several studies have been conducted on E. faecalis and periapical infection. Nowadays, plants used in traditional medicine play a role that is widely appreciated by researchers. One of these herbs is ginger which shows an acceptable antimicrobial effect on E. faecalis. Due to the highly crucial role that irrigation plays in the success of endodontic treatment, a comprehensive survey based on several criteria, namely, scientific, technical, and empirical, is required to address the goal of determining the best endodontic solution. Methodology The most important criteria are antibacterial activity, risks and hazards, cost, and availability. In this study, the analytical network process (ANP), which is a multi-criteria decision-making method, was applied to determine the best endodontic irrigant. Results Several alternatives were investigated using the ANP. In this study, 5.25% sodium hypochlorite (NaOCl) and 2% chlorhexidine were at the top of the list. According to the sensitivity analysis, 10% ethanolic ginger extract showed comparable results to 2.5% NaOCl. Conclusions To carefully prioritize endodontic irrigants a wide range of standards and criteria should be considered. Considering the low risk, great wettability, and active compounds of ginger extract, it can be a promising viable risk-free solution for root canal treatments.


The influence of the known radioprotective compounds on the metabolism of red blood cells. I. Effect of cysteamine on the cellular level of the intermediates and coenzymes.
Cysteamine added to the human blood samples in the final concentration of 6.5 X 10(-3)m, 1,9 X 10(-2) M and 3,8 X 10(-2) M exerts a significant effect on the metabolism of erythrocytes. The chromatographic determination of carbohydrate intermediates and coenzymes in red blood cells indicates that in lower concentration of the drug the rate of anaerobic metabolism of glucose is increased. Higher concentration of cysteamine (3.8 X 10(-3) M) enhances aerobic catabolism of glucose in pentose shunt.


Hypomethylation of the Toll-like receptor-2 gene increases the risk of essential hypertension.
Studies on the etiology of essential hypertension (EH) have demonstrated that chronic inflammation contributes to the onset and development of elevated blood pressure. Toll‑like receptors (TLRs), important immune receptors, serve a role in chronic inflammation and are associated with EH. In the present study, 96 patients with EH, and 96 age‑ and sex‑matched healthy controls were recruited, and eight cytosine‑phosphate‑guanine (CpG) dinucleotides (CpG1‑8) were analyzed using bisulfite pyrosequencing technology. It was observed that the methylation levels of all of the eight CpG dinucleotides were decreased in the EH group compared with the control group; however, only CpG1 (2.83±1.34 vs. 3.44±1.75; P=0.009), CpG6 (3.58±3.64 vs. 8.30±4.13; P<0.001) and CpG8 (8.91±5.32 vs. 11.33±3.87; P<0.001) were significantly different, as demonstrated by paired t‑test analysis. In addition, logistic regression analysis demonstrated that CpG6 hypomethylation was a risk factor of EH (odds ratio=1.10; adjusted P=0.009), and CpG6 methylation level was observed to be negatively correlated with systolic blood pressure (r=‑0.304; P<0.001) and diastolic blood pressure (r=‑0.329; P<0.001). Additionally, receiver operating characteristic curve analysis demonstrated that a methylation level of 7.5% for CpG6 (area under the curve, 0.834; P<0.001) was an appropriate threshold value to predict the risk of EH. With generalized multifactor dimensionality reduction, a potential gene‑gene interaction between CpG6 and CpG8 (P=0.001), and gene‑environment interactions between smoking, alcohol consumption, CpG6, CpG7 and CpG8 (P=0.011), were observed. In conclusion, the results of the present study demonstrated that hypomethylation of the TLR2 promoter, particularly CpG6, was associated with the risk of EH in this population. Additionally, a gene‑gene interaction between CpG6 and CpG8, and interactions between environmental factors, including smoking and alcohol consumption, and CpG6, CpG7 and CpG8, may be associated with the risk of EH.


Fluorescent cellulose nanocrystals/waterborne polyurethane nanocomposites for anti-counterfeiting applications.
The development of eco-friendly anti-counterfeiting materials with high optical transparency and bright luminescence in the aggregate state is tremendously challenging. Herein, waterborne polyurethane/tetraphenylethylene-cellulose nanocrystal (WPU/TPE-CNC) nanocomposite aqueous solutions and films were prepared via direct blending aggregation-induced emission (AIE) active fluorescent CNCs (TPE-CNCs) with WPU and then applied in the anti-counterfeiting field. TPE-CNCs are compatible with WPU and dispersed homogeneously in the nanocomposite aqueous solutions and films. The thermal stability and mechanical properties of these films significantly improved with the increase in the content of TPE-CNCs. WPU/TPE-CNC nanocomposite films display high transparency (above 80%), excellent fluorescence properties, high mechanical strength, and good flexibility and then successfully applied to anti-counterfeit marking. Moreover, the dispersions of the aqueous WPU/TPE-CNC nanocomposite were nearly colorless and demonstrated promise as fluorescent anti-counterfeiting inks. This novel eco-friendly nanocomposite exhibited the potential for applications in anti-counterfeiting, fluorescent transparent paper and coating, fluorescent 3D printing, and optical/sensing devices.


[Masked (atypical) depression in patients with back pain syndrome in outpatient neurological care].
Affective disorders, mainly depression is fast growing problem in highly civilised communities. The literature reports that 30-40% of patients seeking medical advice from specialists (not psychiatrists) in outpatient departments, suffer from these disorders. Many authors mention also diagnostic difficulties in dealing with atypical depression, and draw attention to the fact that this process is often "masked" by chronic pain. In neurological care we find a remarkable group of outpatients with back pain syndrome, mainly cervical and lumbar, with no corresponding lesions found on examination. This enabled us to assume that in some patients presenting with somatic symptoms and therefore referred to a neurologist, the reason of complaints can be depressive disorders. The aim of the study was to verify this hypothesis and to estimate the frequency of masked depression in neurological care. 100 patients were examined in the neurological outpatient department, with the use of the two--Beck and Hamilton--scales of depression evaluation. A statistical analysis of the data thus obtained, showed that: back pain syndrome, as a symptom of depression, occurred in 14% of all patients referred to a neurologist, whereas in 37%--depressive disorders, not diagnosed before, were detected; in 88,2% they were of mild and moderate type. In some patients presenting with somatic symptoms and therefore referred to a neurologist, the reason of complaints are depresive disorders.


Increasing antioxidant activity of procyanidin extracts from the pericarp of Litchi chinensis processing waste by two probiotic bacteria bioconversions.
Litchi chinensis pericarp from litchi processing waste is an important plant source of A-type procyanidins, which were considered a natural dietary supplement because of their high biological activity in vivo. Litchi pericarp oligomeric procyanidins (LPOPCs) did not selectively modify the growth of Streptococcus thermophilus and Lactobacillus casei -01 at concentrations of 0.25 and 0.5 mg/mL, and it was demonstrated that the two strains could transform procyanidins during their log period of growth by two different pathways. S. thermophilus was able to metabolize procyanidin A2 to its isomer, and L. casei could decompose flavan-3-ols into 3,4-hydroxyphenylacetic acid, 4-hydroxyphenylpropionic acid, m-coumaric acid, and p-coumaric acid. The total antioxidant capability (T-AOC) of LPOPCs before and after microbial incubation was estimated, and the results suggested that probiotic bacteria bioconversion is a feasible and efficient method to convert litchi pericarp procyanidins to a more effective antioxidant agent.


Ex Vivo Preservation of Ovine Periosteum Using a Perfusion Bioreactor System.
Periosteum is a highly vascularized membrane lining the surface of bones. It plays essential roles in bone repair following injury and reconstruction following invasive surgeries. To broaden the use of periosteum, including for augmenting in vitro bone engineering and/or in vivo bone repair, we have developed an ex vivo perfusion bioreactor system to maintain the cellular viability and metabolism of surgically resected periosteal flaps. Each specimen was placed in a 3D printed bioreactor connected to a peristaltic pump designed for the optimal flow rates of tissue perfusate. Nutrients and oxygen were perfused via the periosteal arteries to mimic physiological conditions. Biochemical assays and histological staining indicate component cell viability after perfusion for almost 4 weeks. Our work provides the proof-of-concept of ex vivo periosteum perfusion for long-term tissue preservation, paving the way for innovative bone engineering approaches that use autotransplanted periosteum to enhance in vivo bone repair.


Multi-attribute scientific documents retrieval and ranking model based on GBDT and LR.
Scientific documents contain a large number of mathematical expressions and texts containing mathematical semantics. Simply using mathematical expressions or text to retrieve scientific documents can hardly meet retrieval needs. The real difficulty in retrieving scientific documents is to effectively integrate mathematical expressions and related textual features. Therefore, this study proposes a multi-attribute scientific documents retrieval and ranking model based on GBDT (gradient boosting decision tree) and LR (logistic regression) by integrating the expressions and text contained in scientific documents. First, the similarities of the five attributes are calculated, including mathematical expression symbols, mathematical expression sub-forms, mathematical expression context, scientific document keywords and the frequency of mathematical expressions. Next, the GBDT model is used to discretize and reorganize the five attributes. Finally, the reorganized features are input into the LR model, and the final retrieval and ranking results of scientific documents are obtained. The experiment in this study was carried out on the NTCIR dataset. The average value of the final MAP@20 of the scientific document recall was 81.92%. The average value of the scientific document ranking nDCG@20 was 86.05%.


[Diagnosis and treatment of chronic wound infections].
The treatment of chronic wounds is slow and difficult and the presence of an infection can further delay the healing. Diagnosis of this infection is clinical. It must be accompanied by targeted sampling carried out in accordance with a specific technique in order to adapt the treatment as best as possible.


Hydroxychloroquine, Interleukin-6 Receptor Antagonists and Corticoid Treatments of Acute COVID-19 Infection: Psychiatric Symptoms and Mental Disorders 4 Months Later.
Psychiatric symptoms and mental disorders are common after Coronavirus Disease-19 (COVID-19). Some drugs used to treat acute COVID-19 have psychiatric side effects. We assessed the psychiatric symptoms and mental disorders of patients treated for acute COVID-19 with hydroxychloroquine (HCQ), interleukin-6 receptor antagonists (anti-IL-6), and corticoids (CTC). We evaluated 177 patients in a day hospital 4 months after acute infection. In a multivariate analysis, HCQ was associated with significant anxiety symptoms (odds ratio [OR] = 5.9, 95% confidence interval [95% CI] = 1.8-20.0, p = 0.003) and mental disorders (OR = 4.1, 95% CI = 1.2-13.9, p = 0.02). In a bivariate analysis with propensity matched cohorts, HCQ was associated with significant anxiety symptoms (9 patients [50.0%] with significant symptoms in the HCQ group versus 15 [20.1%] in the control group, OR = 3.8, 95% CI = 1.3-11.3, p = 0.01). Anti-IL-6 and CTC were not associated with significant psychiatric symptoms or mental disorders. We recommend monitoring psychiatric symptoms, especially anxiety, in patients treated with HCQ during COVID-19 infection. Further studies with larger samples and prospective assessments are needed to confirm our results.


Trends in antimicrobial susceptibilities among bacterial pathogens isolated from patients hospitalized in European medical centers: 6-year report of the MYSTIC Surveillance Study (1997-2002).
The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program provides antimicrobial susceptibility data. The activity of meropenem and 7 broad-spectrum antimicrobials have been examined against 12645 bacterial isolates from 14 European centers between 1997 and 2002. Cumulative susceptibility rates against all species of Enterobacteriaceae combined were ranked as follows: meropenem (99.9%) > imipenem (97.7%) > ciprofloxacin (86.0%) > piperacillin-tazobactam (85.6%) > ceftazidime (85.4%) > gentamicin (85.4%) > tobramycin (85.0%) > cefotaxime (83.8%). The carbapenems were also found to be the most active of the classes tested against nonfermentative Gram-negative bacilli. Against methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci, all beta-lactams tested (except ceftazidime) had susceptibility rates of > or = 99.0% and > or = 94.3%, respectively. Over the 6-year period, there was no loss of activity or increase in resistance rate for either carbapenem against any of the species tested. These data confirm the continued potency and broad-spectrum activity of meropenem in units where it is actively being prescribed.


Pediatric glioma stem cells: biologic strategies for oncolytic HSV virotherapy.
While glioblastoma multiforme (GBM) is the most common adult malignant brain tumor, GBMs in childhood represent less than 10% of pediatric malignant brain tumors and are phenotypically and molecularly distinct from adult GBMs. Similar to adult patients, outcomes for children with high-grade gliomas (HGGs) remain poor. Furthermore, the significant morbidity and mortality yielded by pediatric GBM is compounded by neurotoxicity for the developing brain caused by current therapies. Poor outcomes have been attributed to a subpopulation of chemotherapy and radiotherapy resistant cells, termed "glioma stem cells" (GSCs), "glioma progenitor cells," or "glioma-initiating cells," which have the ability to initiate and maintain the tumor and to repopulate the recurring tumor after conventional therapy. Future innovative therapies for pediatric HGG must be able to eradicate these therapy-resistant GSCs. Oncolytic herpes simplex viruses (oHSV), genetically engineered to be safe for normal cells and to express diverse foreign anti-tumor therapeutic genes, have been demonstrated in preclinical studies to infect and kill GSCs and tumor cells equally while sparing normal brain cells. In this review, we discuss the unique aspects of pediatric GSCs, including markers to identify them, the microenvironment they reside in, signaling pathways that regulate them, mechanisms of cellular resistance, and approaches to target GSCs, with a focus on the promising therapeutic, genetically engineered oHSV.


Hypoxia-responsive nanoreactors based on self-enhanced photodynamic sensitization and triggered ferroptosis for cancer synergistic therapy.
Photodynamic therapy (PDT), a typical reactive oxygen species (ROS)-dependent treatment with high controllability, has emerged as an alternative cancer therapy modality but its therapeutic efficacy is still unsatisfactory due to the limited light penetration and constant oxygen consumption. With the development of another ROS-dependent paradigm ferroptosis, several efforts have been made to conquer the poor efficacy by combining these two approaches; however the biocompatibility, tumor-targeting capacity and clinical translation prospect of current studies still exist great concerns. Herein, a novel hypoxia-responsive nanoreactor BCFe@SRF with sorafenib (SRF) loaded inside, constructed by covalently connecting chlorin e6 conjugated bovine serum albumin (BSA-Ce6) and ferritin through azobenzene (Azo) linker, were prepared to offer unmatched opportunities for high-efficient PDT and ferroptosis synergistic therapy. The designed BCFe@SRF exhibited appropriate size distribution, stable dispersity, excellent ROS generation property, controllable drug release capacity, tumor accumulation ability, and outstanding biocompatibility. Importantly, the BCFe@SRF could be degraded under hypoxia environment to release BSA-Ce6 for laser-triggered PDT, ferritin for iron-catalyzed Fenton reaction and SRF for tumor antioxidative defense disruption. Meanwhile, besides PDT effects, it was found that BCFe@SRF mediated treatment upon laser irradiation in hypoxic environment not only could accelerate lipid peroxidation (LPO) generation but also could deplete intracellular glutathione (GSH) and decrease glutathione peroxidase (GPX4) expression, which was believed as three symbolic events during ferroptosis. All in all, the BCFe@SRF nanoreactor, employing multiple cascaded pathways to promote intracellular ROS accumulation, presented remarkably outstanding antitumor effects both in vitro and in vivo. BCFe@SRF could serve as a promising candidate for synergistic PDT and ferroptosis therapy, which is applicable to boost oxidative damage within tumor site and will be informative to future design of ROS-dependent therapeutic nanoplatforms.


Human immunodeficiency virus coinfection with hepatitis B virus leads to a decrease in extracellular and intracellular hepatitis B antigen.
Chronic hepatitis B virus (HBV) infection could cause severe liver disease including cirrhosis, hepatocellular carcinoma, and end-stage liver failure in HIV-positive individuals. The available data from clinical studies suggest that HIV infection modulates the HBV-specific T cell response. However, the virological and molecular aspects of HIV-HBV coinfection are currently poorly understood due to the lack of appropriate model systems. In this study, the effect of HIV infection on the life cycle of HBV was explored using an in vitro model system. The present data show that the extracellular and intracellular hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) decrease significantly in HepG2 cells cotransfected with HIV NL4-3 and pHBV1.3 as compared to those cells transfected only with pHBV1.3. Moreover, a significant decrease in HBV DNA and mRNA expression was also observed in the cotransfected cells. HIV Rev protein, an RNA-bound regulatory protein, could significantly decrease the expression levels of extracellular and intracellular HBsAg and HBeAg by mediating the expression of HBV mRNA in cells cotransfected with plasmids containing HIV-1 Rev and pHBV1.3. Further experiments demonstrate that HIV Rev manipulated neither the promoters of HBV nor the nuclear export of HBV mRNA. These results from the in vitro model system might provide clues to further understand the rapid progression of liver disease in HIV-HBV-coinfected patients.


Highly Sensitive and Selective Detection of Nanomolar Ferric Ions Using Dopamine Functionalized Graphene Quantum Dots.
The good stability, low cytotoxicity, and excellent photoluminescence property of graphene quantum dots (GQDs) make them an emerging class of promising materials in various application fields ranging from sensor to drug delivery. In the present work, the dopamine-functionalized GQDs (DA-GQDs) with stably bright blue fluorescence were successfully synthesized for low level Fe(3+) ions detection. The as-synthesized GQDs are uniform in size with narrow-distributed particle size of 4.5 ± 0.6 nm and high quantum yield of 10.2%. The amide linkage of GQDs with dopamine, confirmed by using XPS and FTIR spectra, results in the specific interaction between Fe(3+) and catechol moiety of dopamine at the interfaces for highly sensitive and selective detection of Fe(3+). A linear range of 20 nM to 2 μM with a detection limit of 7.6 nM is obtained for Fe(3+) detection by DA-GQDs. The selectivity of DA-GQDs sensing probe is significantly excellent in the presence of other interfering metal ions. In addition, the reaction mechanism for Fe(3+) detection based on the complexation and oxidation of dopamine has been proposed and validated. Results obtained in this study clearly demonstrate the superiority of surface functionalized GQDs to Fe(3+) detection, which can pave an avenue for the development of high performance and robust sensing probes for detection of metal ions and other organic metabolites in environmental and biomedical applications.


The roles of hepatitis B virus-encoded X protein in virus replication and the pathogenesis of chronic liver disease.
Hepatitis B virus (HBV) is a major cause of chronic liver disease (CLD) and hepatocellular carcinoma (HCC) worldwide. More than 350 million people are at risk for HCC, and with few treatment options available, therapeutic approaches to targets other than the virus polymerase will be needed. This review suggests that the HBV-encoded X protein, HBx, would be an outstanding target because it contributes to the biology and pathogenesis of HBV in three fundamental ways. First, HBx is a trans-activating protein that stimulates virus gene expression and replication, thereby promoting the development and persistence of the carrier state. Second, HBx partially blocks the development of immune responses that would otherwise clear the virus, and protects infected hepatocytes from immune-mediated destruction. Thus, HBx contributes to the development of CLD without virus clearance. Third, HBx alters patterns of host gene expression that make possible the emergence of HCC. The selected literature cited is from the National Library of Medicine (Pubmed and Medline). Understanding the mechanisms, whereby HBx supports virus replication and promotes pathogenesis, suggests that HBx will be an important therapeutic target against both virus replication and CLD aimed at the chemoprevention of HCC.


Compact tunable photonic comb filter on a silicon platform.
We propose and demonstrate a compact wavelength- and bandwidth-tunable photonic comb filter on a silicon platform. It is a Fabry-Perot (FP) cavity fabricated on silicon-on-insulator, which is composed of two cascaded Sagnac loop mirrors (SLMs) with multimode-interferometer-assisted Mach-Zehnder interferometer (MZI) couplers. The effective length of the FP cavity and the reflectivity of the SLMs can be dynamically changed based on thermal-optical effects by tuning three phase shifters along the cavity length and MZI arms, leading to center wavelength tuning and bandwidth tuning of the comb filter. Three tuning cases are investigated. By independently or simultaneously tuning three microheaters, center wavelength tuning with a tuning efficiency of ∼0.017 nm/mW and bandwidth tuning from 4.37 to 27.6 GHz are achieved in the experiment.


Comparison of different modalities for reducing childhood intussusception.
Idiopathic intussusception is an important abdominal emergency in infancy and childhood. Non operative management for treatment is firstly considered due to less invasiveness, less complications and cost effectiveness compared to surgical treatment. This study summarizes our experience in the management of intussusception in children who were referred to a children hospital. A total of 102 children who were diagnosed as having intussusception were referred to one children hospital in Tehran during a period of 10 years, from 1997 to 2007. Reductions were performed upon 57 cases by a radiologist or radiology residents, if there was no medical contraindication. We used chi-square test for analysis. The success rate of reduction was eight out of 13 (61.5%) with barium, nine out of 17 (53.5%) with air and 22 out of 27 (81.5%) with saline (p value=0.116). One patient had recurrence with air reduction. Another case was complicated by peritonitis using barium enema. There was no significant relationship between the success rate of reduction and the type of reduction.


Successful treatment for leg ulcers due to hydroxyurea in a patient with chronic myelogenous leukaemia.
A 51-year-old male who had intractable leg ulcers during treatment for chronic myelogenous leukaemia with hydroxyurea (HU) is reported. His leg ulcers were treated by application of tretinoin tocoferil (TT) ointment after surgical debridement; good results were obtained. Although stopping HU administration is vitally important, surgical debridement and TT application are effective for treating leg ulcers due to HU.


Familial aggregation of dyslexia phenotypes. II: paired correlated measures.
Dyslexia is a common and complex behavioral disorder characterized by unexpected difficulty in learning to read. Psychometric measures used to assess dyslexia often evaluate overlapping processes or abilities. To identify subphenotypes amenable to model-based linkage analyses, we have used careful language phenotyping, familial aggregation analyses of single phenotype measures, and segregation analyses. In the current study, to identify covariates to use in future segregation analyses we examined six pairs of related measures selected from among the most promising candidates in the initial aggregation analyses whose aggregation patterns were most consistent with a genetic basis. For these reciprocal aggregation analyses each measure is evaluated with the paired measure as the covariate to obtain information about the interdependence of the paired measures on shared genetic factors. Six pairs of measures were evaluated: 1) accuracy and efficiency of phonological decoding; 2) phonological nonword memory and written spelling; 3) phonological decoding accuracy and written spelling; 4) inattention ratings and rapid automatized naming for switching letters and numerals (RAS); 5) inattention ratings and oral reading rate; and 6) RAS and oral reading rate. Results of these analyses provide evidence that there may be a genetic contribution to efficiency of phonological decoding in addition to the genetic contribution it shares with accuracy of phonological decoding, a genetic contribution to phonological nonword memory in addition to the genetic contribution it shares with written spelling, a genetic contribution to written spelling in addition to the genetic contribution it shares with accuracy of phonological decoding, and a genetic contribution to inattention ratings in addition to the genetic contribution it shares with either RAS or oral reading rate.


Autogenous Bone Marrow Aspirate Coated Synthetic Hydroxyapatite for Reconstruction of Maxillo-Mandibular Osseous Defects: A Prospective Study.
This prospective study was conducted to evaluate the bone regeneration capacity of synthetic hydroxyapatite mixed with autogenous bone marrow aspirate when used as a bone graft substitute in maxillo-mandibular osseous defects. This study included nine patients with histopathalogically proven benign osteolytic lesions in maxilla and mandible that were treated with enucleation or marginal resection followed by bone marrow aspirate coated synthetic biphasic hydroxyapatite (hydroxyapatite and beta tricalcium phosphate) graft placement. Incorporation of graft was assessed based on Irwin's radiologic staging. The efficacy of graft to form new bone was radiologically evaluated by observing the sequential changes of density at grafted site using gray scale level histogram which was processed in adobe photoshop 7.0 elements. Clinical assessment of recipient and donor sites was done. Based on Irwin's radiologic staging, at 6 month follow up period, obvious incorporation of graft with new bone was observed. Sequential changes in bone density measured by gray scale histogram revealed initial resorption followed by replacement of BMA coated hydroxyapatite with new bone formation. None of the patients eventually had complications like infection, wound dehiscence, graft loss at recipient sites at 6 months follow up period. Autogenous bone marrow aspirate in combination with synthetic hydroxyapatite is an effective option for accelerating bone regeneration in small to moderate sized jaw bone defects. This mixture provides all the three critical elements needed for bone regeneration (osteogenesis, osteoinduction and osteoconduction) with an added advantage of obviating donor site morbidity.


Induced sputum in the management of COPD: clinical implications.
Sputum induction can be used as a non-invasive technique to investigate airway inflammation in asthma and COPD. We reported the case of a 68 year old man with COPD, stage III GOLD, that underwent sputum induction during two exacerbation episodes. The first cell count showed a typical sputum neutrophilia, whereas the second showed sputum eosinophilia. On the basis of sputum cellularity, we decided to treat the first episode with a course of antibiotics and the second exacerbation with a course of antibiotics and oral steroids. The patient showed improvement in both cases, obtaining clinical stabilisation. The induced sputum cell count could be a useful technique in a clinical setting to evaluate the cellular characteristics of airway inflammation during COPD exacerbation and modulate the antinflammatory therapy.


The molecular basis of gamete recognition in mice and humans.
Successful fertilization heralds the onset of development and requires both gamete recognition and a definitive block to polyspermy. Sperm initially bind and penetrate the extracellular zona pellucida (ZP) that surrounds ovulated eggs, but are unable to bind the zona surrounding preimplantation embryos. The ZP of humans is composed of four (ZP1-4) and that of mouse three (ZP1-3) glycoproteins. Models for gamete recognition developed in mice had proposed that sperm bind to ZP3 glycans. However, phenotypes observed in genetically engineered mice are not consistent with this widely accepted model. More recently, taking advantage of the observation that human sperm do not bind to mouse eggs, human ZP2 was defined as the zona ligand in transgenic mouse models using gain-of-function assays. The sperm-binding site is an N-terminal domain of ZP2 that is cleaved by ovastacin, a metalloendoprotease released from egg cortical granules following fertilization. Proteolysis of this docking site provides a definitive block to polyspermy as sperm bind to uncleaved, but not cleaved ZP2 even after fertilization and cortical granule exocytosis. While progress has been made in defining the ZP ligand, less headway has been made in identifying the cognate sperm receptor. Although a number of sperm receptor candidates have been documented to interact with specific proteins in the ZP in vitro, continued fertility after genetic ablation of the cognate gene indicates that none are essential for gamete recognition. These on-going investigations inform reproductive medicine and suggest new therapies to improve fertility and/or provide contraception, thus expanding reproductive choices for human couples.


Free amino nitrogen concentration correlates to total yeast assimilable nitrogen concentration in apple juice.
Yeast assimilable nitrogen (YAN) is essential for yeast growth and metabolism during apple (Malus x domestica Borkh.) cider fermentation. YAN concentration and composition can impact cider fermentation kinetics and the formation of volatile aroma compounds by yeast. The YAN concentration and composition of apples grown in Virginia, USA over the course of two seasons was determined through analysis of both free amino nitrogen (FAN) and ammonium ion concentration. FAN was the largest fraction of YAN, with a mean value of 51 mg N L-1 FAN compared to 9 mg N L-1 ammonium. Observed YAN values ranged from nine to 249 mg N L-1, with a mean value of 59 mg N L-1. Ninety-four percent of all samples analyzed in this study contained <140 mg N L-1 YAN, a concentration generally considered the minimum level needed in grape-based wines for yeast to fully utilize all of the fermentable sugars. FAN concentration was correlated with total YAN concentration, but ammonium concentration was not. Likewise, there was no correlation between FAN and ammonium concentration.


FILIP1L Loss Is a Driver of Aggressive Mucinous Colorectal Adenocarcinoma and Mediates Cytokinesis Defects through PFDN1.
Aneuploid mucinous colorectal adenocarcinoma (MAC) is an aggressive subtype of colorectal cancer with poor prognosis. The tumorigenic mechanisms in aneuploid MAC are currently unknown. Here we show that downregulation of Filamin A-interacting protein 1-like (FILIP1L) is a driver of MAC. Loss of FILIP1L increased xenograft growth, and, in colon-specific knockout mice, induced colonic epithelial hyperplasia and mucin secretion. The molecular chaperone prefoldin 1 (PFDN1) was identified as a novel binding partner of FILIP1L at the centrosomes throughout mitosis. FILIP1L was required for proper centrosomal localization of PFDN1 and regulated proteasome-dependent degradation of PFDN1. Importantly, increased PFDN1, caused by downregulation of FILIP1L, drove multinucleation and cytokinesis defects in vitro and in vivo, which were confirmed by time-lapse imaging and 3D cultures of normal epithelial cells. Overall, these findings suggest that downregulation of FILIP1L and subsequent upregulation of PFDN1 is a driver of the unique neoplastic characteristics in aggressive aneuploid MAC. SIGNIFICANCE: This study identifies FILIP1L as a tumor suppressor in mucinous colon cancer and demonstrates that FILIP1L loss results in aberrant stabilization of a centrosome-associated chaperone protein to drive aneuploidy and disease progression.


What do UK medical students value most in their careers? A discrete choice experiment.
Many individual- and job-related factors are known to influence medical careers decision making. Previous research has extensively studied medical trainees' (residents') and students' views of the factors that are important. However, how trainees and students trade off these factors at times of important careers-related decision making is under-researched. Information about trade-offs is crucial to the development of effective policies to enhance the recruitment and retention of junior doctors. Our aim was to investigate the strength of UK medical students' preferences for the characteristics of training posts in terms of monetary value. We distributed a paper questionnaire that included a discrete choice experiment (DCE) to final-year medical students in six diverse medical schools across the UK. The main outcome measure was the monetary value of training post characteristics, based on willingness to forgo and willingness to accept extra income for a change in each job characteristic calculated from regression coefficients. A total of 810 medical students answered the questionnaire. The presence of good working conditions was by far the most influential characteristic of a training position. Medical students consider that, as newly graduated doctors, they will require compensation of an additional 43.68% above average earnings to move from a post with excellent working conditions to one with poor working conditions. Female students value excellent working conditions more highly than male students, whereas older medical students value them less highly than younger students. Students on the point of completing medical school and starting postgraduate training value good working conditions significantly more than they value desirable geographical location, unit reputation, familiarity with the unit or opportunities for partners or spouses. This intelligence can be used to address the crisis in workforce staffing that has developed in the UK and opens up fruitful areas for future research across contexts and in terms of examining stated preferences versus actual career-related behaviour.


Isolation of Extracellular Vesicles From Microalgae: A Renewable and Scalable Bioprocess.
Extracellular vesicles (EVs) play a crucial role as potent signal transducers among cells, with the potential to operate cross-species and cross-kingdom communication. Nanoalgosomes are a subtype of EVs recently identified and isolated from microalgae. Microalgae represent a natural bioresource with the capacity to produce several secondary metabolites with a broad range of biological activities and commercial applications. The present study highlights the upstream and downstream processes required for the scalable production of nanoalgosomes from cultures of the marine microalgae Tetraselmis chuii. Different technical parameters, protocols, and conditions were assessed to improve EVs isolation by tangential flow filtration (TFF), aiming to enhance sample purity and yield. The optimization of the overall bioprocess was enhanced by quality control checks operated through robust biophysical and biochemical characterizations. Further, we showed the possibility of recycling by TFF microalgae cells post-EVs isolation for multiple EV production cycles. The present results highlight the potential of nanoalgosome production as a scalable, cost-effective bioprocess suitable for diverse scientific and industrial exploitations.


Hodgkin's disease in children.
From 1921 to 1973, 106 children with Hodgkin's disease under the age of 17 years were seen at Roswell Park Memorial Institute and were analyzed retrospectively. Evaluation was separated into three eras: 1921-1949 (early era), 1950-1964 (middle era), and 1965-1973 (recent era). In the early era, suboptimal radiation therapy was employed. In the middle era, radiation therapy techniques were improved, and single-agent chemotherapy was introduced. In the recent era, multiagent chemotherapy routines were frequently used; aggressive external megavoltage radiation therapy became routine in conjunction with improvement in staging procedures. The best survival was observed in the recent era where five-year survival of 96% was noted in early stage disease. Favorable prognostic features included: younger age group (5-9 years), female sex, lymphocytic predominant histology, early stage disease, and complete response to therapy. Nodular sclerosing and mixed cell types had an equal prognosis. The concept of involved area radiotherapy along with combination chemotherapy appears a reasonable approach in children and should be tested in a randomized study against more extensive radiotherapy techniques in early stage disease.


Effect of a two-step placement procedure on the dislocation resistance of a methacrylate resin-based root canal sealer: a proof of concept.
To investigate whether the placement of a methacrylate root canal sealer or a conventional epoxy root canal sealer in two steps increases their dislocation resistance when compared to a one-step placement procedure. Eighty single-rooted teeth were randomly allocated to 4 groups (n=20). All canals were instrumented to size 40, 0.06 taper and irrigated according to a standardized protocol. Root canal filling was conducted as follows: group 1: methacrylate sealer placed in two steps; group 2: methacrylate sealer placed in one step; group 3: epoxy sealer placed in two steps; group 4: epoxy sealer placed in one step. After setting, thin slices at different root levels were obtained and submitted to push-out testing. RESULTS were analyzed with non-parametric tests to compare the two-step procedures to their one-step counterparts. Failure modes were determined by stereomicroscopy. Random untested methacrylate sealer specimens were also examined with scanning electron microscopy. At each root level, dislocation resistance was significantly higher for the two-step procedure than for the one-step procedure using the methacrylate sealer (p=0.003, p=0.005, p<0.001) but not the epoxy sealer (p=0.83, p=0.1, p=0.06). Among root levels, there were no significant differences in dislocation resistance in the methacrylate sealer two-step group, while all other groups showed differences. A two-step placement procedure resulted in significantly higher dislocation resistance for the methacrylate sealer but not for the epoxy sealer.


Single-molecule manipulation and detection.
Compared to conventional ensemble methods, studying macromolecules at single-molecule level can reveal extraordinary clear and even surprising views for a biological reaction. In the past 20 years, single-molecule techniques have been undergoing a very rapid development, and these cutting edge technologies have revolutionized the biological research by facilitating single-molecule manipulation and detection. Here we give a brief review about these advanced techniques, including optical tweezers, magnetic tweezers, atomic force microscopy (AFM), hydrodynamic flow-stretching assay, and single-molecule fluorescence resonance energy transfer (smFRET). We are trying to describe their basic principles and provide a few examples of applications for each technique. This review aims to give a rather introductory survey of single-molecule techniques for audiences with biological or biophysical background.


Muscle metabolic alterations induced by genetic ablation of 4E-BP1 and 4E-BP2 in response to diet-induced obesity.
In recent years, several studies reported the role of eIF4E-binding proteins (4E-BPs) on the development of diet-induced obesity and insulin resistance. Our aim was to investigate the effect of 4E-BP protein deletion on lipid accumulation and metabolism in skeletal muscle in response to a high-fat diet induced obesity in 4E-BP1/2 DKO mice. Diet-induced obesity engendered increased ectopic accumulation of lipotoxic species in skeletal muscle of 4E-BP1 and 4E-BP2 double knockout mice (4E-BP1/2 DKO), namely diacylglycerols and ceramides. Increased lipid accumulation was associated with alterations in the expression of genes involved in fatty acid transport (FATP, CD36), diacylglycerol/triacylglycerol biosynthesis (GPAT1, AGPAT1, DGAT1), and β-oxidation (CPT1b, MCAD). Diet-induced obesity resulted in increased lean mass and muscle in 4E-BP1/2 DKO mice despite the development of a more severe systemic insulin resistance. Since increased expression of genes of several proteolytic systems (MuRF1, atrogin/MAFbx, and cathepsin-l) in 4EBP1/2 DKO skeletal muscle was reported, the increase of skeletal muscle mass in 4E-BP1/2 DKO mice suggests that ablation of 4E-BPs compensate with activation of muscle anabolism. These findings indicate that 4E-BP proteins may prevent excess lipid accumulation in skeletal muscle and suggest that 4E-BPs are key regulators of muscle homeostasis regardless of insulin sensitivity.


Multiple granulocytic sarcomas in essential thrombocythemia.
A 59-year-old woman was diagnosed with essential thrombocythemia in 1988 and had been treated with hydroxyurea, mitobronitol, busulfan, and ranimustine, in that order. Hepatosplenomegaly, low-grade fever, and body weight loss manifested, and a few blasts were noted in the peripheral blood studied in March 2002. A biopsied specimen of the bone marrow showed myelofibrosis but not a leukemia in August 2004. An abnormal karyotype with der(1; 13) appeared for the first time. She was treated with low-dose prednisolone. In January 2005, she experienced left hip joint pain, and magnetic resonance scanning showed a tumoral lesion in the femoral head. Histological diagnosis of the biopsied mass revealed that it was a granulocytic sarcoma, and radiotherapy was performed. In April 2005, bone scintigraphy showed multiple lesions. She became febrile and red blood cell transfusion-dependent with hepatosplenomegaly and a small number of circulating blasts. Intravenous cytarabine (low dose) and etoposide relieved the fever and hepatosplenomegaly; however, she developed a pathologic fracture of the right humerus. An additional karyotypic abnormality (7q22 deletion) was noted. She subsequently died of infection. Granulocytic sarcoma is very rare in essential thrombocythemia, and this patient may be the first reported case of essential thrombocythemia that developed multiple lesions and a pathologic fracture without transformation to overt leukemia.


Anti-drug-related antibodies in nonthrombocytopenic cardiac patients.
Drug-related antibodies (quinidine, hydrochlorothiazide, and digoxin) were studied using the 51Cr platelet lysis test and a recently introduced simplified platelet factor 3 assay in a total of 109 patients admitted to a coronary care unit. Quinidine antibodies were found in 16 (14.7%), hydrochlorothiazide antibodies in six (5.5%) and digoxin antibodies in two (1.8%) of 109 patients. All patients had normal hematologic data, including platelet counts. There was a significantly high incidence of quinidine antibodies in male patients (p less than 0.02), despite the previous report that quinidine-induced purpura was seen predominantly in female patients. Ten patients (9.2%) had antiplatelet antibodies. The simplified platelet factor 3 assay can easily be done in most laboratories and appears as sensitive as the 51Cr platelet lysis test. The high incidence of drug-related or antiplatelet antibodies in hematologically asymptomatic patients may indicate the presence of an insidious, compensated thrombolytic state in many patients.


Differential Predictive Roles of A- and B-Type Nuclear Lamins in Prostate Cancer Progression.
Prostate cancer (PCa) is the most common cancer among men in western countries. While active surveillance is increasingly utilized, the majority of patients are currently treated with radical prostatectomy. In order to avoid over-treatment, there is an indisputable need for reliable biomarkers to identify the potentially aggressive and lethal cases. Nuclear intermediate filament proteins called lamins play a role in chromatin organization, gene expression and cell stiffness. The expression of lamin A is associated with poor outcome in colorectal cancer but to date the prognostic value of the lamins has not been tested in other solid tumors. We studied the expression of different lamins with immunohistochemistry in a tissue microarray material of 501 PCa patients undergoing radical prostatectomy and lymph node dissection. Patients were divided into two staining categories (low and high expression). The correlation of lamin expression with clinicopathological variables was tested and the association of lamin status with biochemical recurrence (BCR) and disease specific survival (DSS) was further analyzed. Low expression of lamin A associated with lymph node positivity (p<0.01) but not with other clinicopathological variables and low expression had a borderline independent significant association with DSS (HR = 0.4; 95% CI 0.2-1.0; p = 0.052). Similarly, low lamin C expression associated with poorer survival (HR = 0.2; 95% CI 0.1-0.6; p = 0.004). Lamin B1 expression did not associate with clinicopathological variables but high expression independently predicted BCR in multivariable Cox regression analysis (HR = 1.8; 95% CI 1.1-2.9; p = 0.023). Low expression of lamin B2 correlated with lymph node positivity (p<0.01) and predicted unfavorable DSS (HR = 0.4; 95% CI 0.2-1.0; p = 0.047). These results suggest differential roles for lamins in PCa progression. Reduced amounts of lamin A/C and B2 increase risk for lymph node metastasis and disease specific death possibly through increased nuclear deformability while high expression of lamin B1 predicts disease recurrence.


Design and preparation of pH-sensitive cytotoxic liposomal formulations containing antitumor colchicine analogues for target release.
Herein, we describe the synthesis of pH-sensitive lipophilic colchicine prodrugs for liposomal bilayer inclusion, as well as preparation and characterization of presumably stealth PEGylated liposomes with above-mentioned prodrugs. These formulations liberate strongly cytotoxic colchicinoid derivatives selectively under slightly acidic tumor-associated conditions, ensuring tumor-targeted delivery of the compounds. The design of the prodrugs is addressed to pH-triggered release of active compounds in the slight acidic media, that corresponds to tumor microenvironment, while keeping sufficient stability of the whole formulation at physiological pH. Correlations between the structure of the conjugates, their hydrolytic stability, colloidal stability, ability of the prodrug retention in the lipid bilayer are described. Several formulations were found promising for further development and in vivo investigations.


Significant improvement of bone mineral density by denosumab treatment in Japanese osteoporotic patients following breast cancer treatment.
The aim of this study was to evaluate the effects of denosumab in patients with osteoporosis (OP) and non-metastatic breast cancer following treatment of 1) surgery, 2) surgery and aromatase inhibitors, and 3) surgery, aromatase inhibitors, and anti-cancer agents, compared with those in primary OP patients. In this retrospective 24-month study, patients were divided into the primary OP group (34 cases) or OP receiving breast cancer treatment group (breast cancer group; 17 cases). We measured serum calcium, whole parathyroid hormone (PTH), 1,25OH2D3, bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase-5b (TRACP-5b), and bone mineral density (BMD) of the lumbar 1-4 vertebrae (L-BMD) and bilateral total hips (H-BMD) for 24 months. The percent changes of serum calcium in the breast cancer group were significantly lower than those in the primary OP group at 1 week, 1 and 12 months. The percent changes of whole PTH in the primary OP group were significantly lower than those in the breast cancer group at 2 and 4 months. Significant differences were found between the groups at 18 months (-34.5% in the primary OP group and -52.6% in the breast cancer group, respectively) for the percent changes of BAP. Significant differences were found between the groups at 12, 18, and 24 months (-39.7% in the primary OP group and -64.0% in the breast cancer group at 24 months, respectively) for the percent changes of TRACP-5b. The percent changes of L-BMD and H-BMD were significantly increased at 12, 18, and 24 months in both the primary OP group (7.0% and 4.7% at 24 months, respectively) and breast cancer group (8.0% and 5.4% at 24 months, respectively), compared with pre-treatment levels. Significant differences were not found between the groups for the percent changes of L-BMD and H-BMD. Denosumab significantly increased L-BMD and H-BMD to comparable degrees in both groups; therefore, it represents a good therapeutic option for OP receiving breast cancer treatment as well as primary OP. Also, vitamin D supplementation is required due to the potential hypocalcemia, and estrogen may be responsible for the decrease of serum calcium in the breast cancer patients.


Molecular-sieving capabilities of mesoporous carbon membranes.
The size-sieving properties of a mesoporous carbon membrane were studied via molecular permeation and cyclic voltammetry experiments. Two phenomena, simple diffusion and electrochemically aided diffusion, were investigated. Molecular diffusion through the membrane was caused by a concentration gradient across the membrane and was facilitated by electrosorption of ions under an externally applied electric field. The diffusion of molecules transported through the membrane was characterized by the values of permeability and apparent diffusion coefficient in the membrane. Because larger molecules are more restricted in terms of penetrating the pores, the size-based selectivity of the mesoporous carbon membrane could be readily observed. For example, in the two-component permeation experiment, a high selectivity (alpha=56.9) of anilinium over Rhodamine B was found. It is inferred that the diffusive transport of the larger Rhodamine B molecules with a more extensive retardation comes from the competitive mechanism between the two kinds of molecules in accessing the pore. A series of voltammetric experiments involving a mesoporous carbon membrane immersed in various electrolytes with ions of different sizes allowed the observation of ion-exclusion phenomena. It was found that the size effect is significant for electrochemically aided diffusion and electrosorption processes. The number of cations inside the pores of the membrane decreases with increasing cation size. This phenomenon is due to the size-exclusion effect, which could be demonstrated by the values of electrical double-layer capacitance for sodium, magnesium, and tetrahexylammonium cations, at potentials ranging from negative values to the point of zero charge, corresponding to 86.7, 73.1, and 50.0 F/g, respectively. The findings of this work manifest that the relationship between the pore size and the dimensions of the molecules determines the transport and sorption behavior of nanoporous carbon materials.


[Treatment of overtime avulsion of scalp with split thickness scalp skin grafting: 7 cases of reports].
To investigate a treatment method for overtime avulsion of scalp. Form October 1992 to July 2001, we treated 7 cases of avulsed scalp, which had been wounded more than 12 hours and accompanied with shock and head wound, with split thickness scalp skin grafting. Except for partial necrosis of scalp in center of bare area of skull, more than 90% of grafting split thickness scalp skin survived in 4 cases and more than 80% in 3 cases, and presented satisfactory appearance during following up. The bare area had no periosteum above 4 cm in diameter needed to graft split thickness skin after skull was covered granulation tissue. The limits of time of scalp skin grafting will be prolonged as long as the processes are settled properly to maintain the skin of body.


Transmesenteric approach for laparoscopic endoscopic cooperative surgery for a duodenal adenoma located in the third portion of the duodenum.
We report our experience in a patient with adenoma located in the horizontal part of the duodenum, which was effectively treated with the transmesenteric laparoscopic endoscopic cooperative surgery (LECS) approach. This approach, which entails incising the mesentery of the colon, simplified laparoscopic access to the horizontal part of the duodenum, which was minimally mobilized. Thus, the bulb and descending part of the duodenum were fixed to the retroperitoneum, facilitating stable handling of the endoscope and enabled safe and effective excision of an adenoma located in the horizontal part of the duodenum. This approach enabled safe and effective excision of an adenoma located in the horizontal part of the duodenum. The advantages of this method include a secure field of view, lower probability of damage to large vessels, and minimizing the defect to the intestine caused by the incision.


Another approach toward over 100,000-fold sensitivity increase in capillary electrophoresis: electrokinetic supercharging with optimized sample injection.
Electrokinetic supercharging (EKS) is a powerful and practical method for multifold in-line concentration of various analytes prior to capillary electrophoresis (CE) analysis. However, a problem of insufficient sensitivity has always existed when trace analyte quantification by EKS-CE is a target, especially when coupled with conventional detectors. Normally this requires a greatly increased amount of analyte injected without separation degradation. In this contribution, we have shown that it is possible to substantially improve analyte loading and hence CE method detectability by modifying sample introduction configuration. The volume of sample vial was increased (from typical 500 μL to 17 mL), the common wire electrode was replaced by a ring electrode, and the sample solution was stirred. With these alterations, more analyte ions are accumulated within the effective electric field during electrokinetic injection and then maintained as focused zones due to transient isotachophoresis. The versatility of the customized EKS-CE approach for sample concentration was demonstrated for a mixture of seven rare-earth metal ions with an enrichment factor of 500 000 giving detection limits at or below 1 ng/L. These detection limits are over 100 000 times better than can be achieved by normal hydrodynamic injection, 1000 times better than the sensitivity thresholds of inductively coupled plasma atomic emission spectrometry (ICP-AES), and even close to those of inductively coupled plasma mass spectrometry (ICPMS).


Potential of repairing ischemically damaged kidneys ex vivo.
Therapies that would accelerate recovery from ischemic injury could positively impact the number of kidneys procured from non-heart-beating donors. An acellular warm (32 degrees C) perfusion was used to deliver growth factors to canine kidneys damaged by 2 hours of warm ischemia. Fibroblast growth factors 1 and 2 were selected for activation of the tyrosine kinases because of their known receptor-specific binding in the kidney, metabolic regulation, and mitogenic effect. During 24 hours of ex vivo perfusion at near-normothermia, oxidative metabolism was sufficiently restored to the ischemically damaged tissue to support upregulation of cellular processes dependent on new synthesis. The junctional integrity protein, ZO-1 was used to determine recovery of cytoskeletal integrity. The upregulation of proliferating cell nuclear antigen was used as a marker for recovery of synthetic functions. This modulation of both injury and repair proteins in the damaged kidneys was dependent on new synthesis. The observed modulation resulting in normalization of the cytoskeletal integrity correlated with outcomes in that when the "repaired" kidneys were reimplanted, they provided life-sustaining function. In contrast, when warm ischemically damaged control kidneys without treatment, with subsequent hypothermic perfusion or warm perfused in the absence of growth factors, were reimplanted the result was nonviability. The results of this study suggest that the administration of growth factors during 24 hours of near-normothermic, acellular perfusion, in the absence of concordant inflammation, triggers pathways for new synthesis leading to cellular recovery rather than resulting in cell death.


Visualization of unconstrained negative supercoils of DNA on polytene chromosomes of Drosophila.
Bulk DNA within the eukaryotic genome is torsionarily relaxed. However, unconstrained negative supercoils of DNA have been detected in few local domains of the genome through preferential binding of psoralen. To make a genome-wide survey for such domains, we introduced biotinylated psoralen into Drosophila salivary glands and visualized it on polytene chromosomes with fluorescent streptavidin. We observed bright psoralen signals on many transcriptionally active interbands and puffs. Upon heat shock, the signals appeared on heat-shock puffs. The signals were resistant to RNase treatment but disappeared or became faint by previous nicking of DNA or inhibition of transcription with alpha-amanitin. These data show that transcription-coupled, unconstrained negative supercoils of DNA exist in approximately 150 loci within the interphase genome.


Evolution of conditional cooperation in collective-risk social dilemma with repeated group interactions.
The evolution and long-term sustenance of cooperation has consistently piqued scholarly interest across the disciplines of evolutionary biology and social sciences. Previous theoretical and experimental studies on collective risk social dilemma games have revealed that the risk of collective failure will affect the evolution of cooperation. In the real world, individuals usually adjust their decisions based on environmental factors such as risk intensity and cooperation level. However, it is still not well understood how such conditional behaviours affect the evolution of cooperation in repeated group interactions scenario from a theoretical perspective. Here, we construct an evolutionary game model with repeated interactions, in which defectors decide whether to cooperate in subsequent rounds of the game based on whether the risk exceeds their tolerance threshold and whether the number of cooperators exceeds the collective goal in the early rounds of the game. We find that the introduction of conditional cooperation strategy can effectively promote the emergence of cooperation, especially when the risk is low. In addition, the risk threshold significantly affects the evolutionary outcomes, with a high risk promoting the emergence of cooperation. Importantly, when the risk of failure to reach collective goals exceeds a certain threshold, the timely transition from a defective strategy to a cooperative strategy by conditional cooperators is beneficial for maintaining high-level cooperation.


Treatment refusal among patients with psoriasis.
Treatment refusal, which is defined as a patient actively refusing to take treatment despite physician recommendations, has never been evaluated in psoriasis. To investigate refusal of topical treatments by patients living with psoriasis in France. Using responses to an internet study, participants who refused topical treatment (n = 50) were compared to those who applied topical treatment (n = 205). Participants undergoing phototherapy, biotherapy, and oral treatment were excluded. Spearman rank correlations completed by Fisher's exact tests and Student's t-tests were performed. Comorbidities, localization of lesions, and symptoms associated with psoriasis were not significant predictors of treatment refusal. Compared to patients who accepted treatment, more patients who refused treatment believed that psoriasis is not manageable (80.0% versus 61.5%; p = 0.01), that psoriasis treatments never work (58.0% versus 27.5%; OR: 2.09 p < 0.0001), and that all creams have the same effects (54.0% versus 31.7%; OR: 1.7, p = 0.003). Among patients who reported seeking medical attention from physicians, more patients in the treatment refusal group reported some level of dissatisfaction with their relationship with their physician than in the treatment acceptance group. The validity of the self-reported treatment refusal could not be evaluated. Treatment refusal is an important element to be taken into consideration in the management of psoriasis.


Intrathecal Morphine and Oral Analgesics Provide Safe and Effective Pain Control After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.
Retrospective comparative study. The aim of this study was to demonstrate that intrathecal morphine (ITM) and oral analgesics provide effective pain control after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS), and this protocol has a low complication rate so patients can be admitted to a general care floor. Previous studies have shown that ITM combined with intravenous patient-controlled analgesia or epidural infusion (EPI) provides effective pain control after PSF for AIS. Owing to concerns for respiratory depression, ITM patients were routinely admitted to the intensive care unit (ICU) postoperatively. There are little data on ITM combined with oral analgesics. We identified AIS patients aged 10 to 17 years who had undergone PSF. Twenty-eight patients who received ITM were matched to 28 patients who received a hydromorphone EPI. The ITM group received oral oxycodone starting at 16 hours postinjection. The EPI group received oxycodone after the epidural catheter was removed on postoperative day 2. Pain scores, adverse events, and length of stay were recorded. A higher number of EPI patients received fentanyl (11 vs. 3, P = 0.014) in the post-anesthesia care unit (PACU). The ITM group had lower pain scores between PACU discharge and midnight (mean 2.9 vs. 4.2, P = 0.034). Pain scores were similar during the remaining postoperative periods. All ITM patients transitioned to oxycodone without intravenous opioids. Time to ambulation (19.9 vs. 26.5 hours, P = 0.010) and Foley catheter removal (21.3 vs. 41.9 hours, P < 0.001) were earlier in the ITM patients. Length of hospital stay was shorter in the ITM group (3.1 vs. 3.5 days, P = 0.043). Adverse events occurred at similar rates in both groups. ITM and oral analgesics provide safe and effective pain control after PSF for AIS. Routine postoperative admission to the ICU is not necessary. 3.


Medical management of benign prostatic hyperplasia with androgen suppression.
Many types of nonsurgical therapy, including balloon dilation, hyperthermia, adrenergic blockade, and hormonal therapy, have been used for the treatment of benign prostatic hyperplasia (BPH). Antiandrogen therapy has been the most extensively studied form of hormonal treatment for BPH, although estrogens, antiestrogens, and antiprolactin agents have also been used (Scott and Coffey: Vitam Horm 33:439-465, 1975). The theoretical basis of antiandrogen therapy will be reviewed along with a summary of relevant clinical trials. Recent advances in the development of agents that more selectively inhibit the androgen-dependent growth of the prostate will be presented.


A Dynamic Structure of Social Trait Space.
Facial appearance evokes robust impressions of other people's personality traits. Recent research suggests that the trait space arising from face-based impressions shifts due to context and social cognitive factors. We suggest a novel framework in which multiple bottom-up and top-down processes mutually determine a dynamic rather than fixed trait space.


Development of small molecule biosensors by coupling the recognition of the bacterial allosteric transcription factor with isothermal strand displacement amplification.
Here, we demonstrate an easy-to-implement and general biosensing strategy by coupling the small-molecule recognition of the bacterial allosteric transcription factor (aTF) with isothermal strand displacement amplification (SDA) in vitro. Based on this strategy, we developed two biosensors for the detection of an antiseptic, p-hydroxybenzoic acid, and a disease marker, uric acid, using bacterial aTF HosA and HucR, respectively, highlighting the great potential of this strategy for the development of small-molecule biosensors.


Estonian adverse events study for multimorbid patients using Estonian Trigger Tool (MUPETT-MUltimorbid Patients-Estonian Trigger Tool). Development of Estonian trigger tool for multimorbid patients. A study protocol for mixed-methods study.
It is widely recognized that providing healthcare may produce harm to the patient. Different approaches have been developed to measure the burden of adverse events (AEs) to plan and measure the effects of interventions. One of the most widely used instruments is the Trigger Tool, which has previously been modified to be used on various settings and translated into many languages. Multimorbidity complicates care and may increase the number of AEs patients experience. Currently there is no instrument designed to measure AEs in multimorbid patients. In Estonia, there is currently no validated instrument to measure the burden of AEs. The aim of this study will be evaluating the characteristics and ocurrence of AEs in multimorbid patients in hospitalised internal medicine patients of Estonia, and describes the development of a trigger tool for this purpose. We will search for the evidence on measuring AEs in the population of multimorbid patients focusing on trigger tools, and synthesize the data. Data collection of the triggers from the literature will be followed by translating triggers from English to Estonian. An expert multidisciplinary panel will select the suitable triggers for this population. Trigger tool will be pre-tested to assess agreement among professionals and usability of the tool. Validation will be done using 90 medical records. A cross-sectional study in internal medicine departments of two Estonian tertiary care hospitals will be performed to identify the frequency and characteristics of AEs in 960 medical records. We will also provide preventability potential and influencing factors. Results will be disseminated to healthcare providers and stakeholders at national and international conferences, and as a doctoral medical thesis.


Ultrasound cardiac output units.
We evaluated 2 dedicated CO US units that calculate CO for teenage and adult ranges. We also tested a unit designed for use on neonatal to pediatric patients and discussed this device separately. Because of the limitations of US technology, we found these units to be best suited for trending CO; however, the utility of US CO for this application far outweighs its limitations.


Effects of Bi-Sn-Pb Alloy and Ball-Milling Duration on the Reactivity of Magnesium-Aluminum Waste-Based Materials for Hydrogen Production.
In the present study, composite materials were elaborated of mixed scrap of Mg-based casting alloys and low melting point Bi-Sn-Pb alloy by high energy ball milling, and their reactivity in NaCl solution with hydrogen release was tested. The impacts of the additive content and ball milling duration on their microstructure and hydrogen generation performance were investigated. Scanning electron microscopy (SEM) analysis revealed significant microstructural transformations of the particles during milling, and X-ray diffraction analysis (XRD) proved the formation of new intermetallic phases Mg3Bi2, Mg2Sn, and Mg2Pb. The said intermetallic phases were anticipated to act as 'microcathodes' enhancing galvanic corrosion of the base metal. The dependency of the samples' reactivity on the additive content and milling duration was determined to be nonmonotonic. For the samples with 0, 2.5, and 5 wt.% Rose alloy, ball-milling during 1 h provided the highest hydrogen generation rates and yields (as compared to 0.5 and 2 h), while in the case of the maximum 10 wt.%, the optimal time shifted to 0.5 h. The sample activated with 10 wt.% Rose alloy for 0.5 h provided the highest 'metal-to-hydrogen' yield and rapid reaction, thus overperforming those with lower additive contents and that without additives.


Excellent performance of cobalt-impregnated activated carbon in peroxymonosulfate activation for acid orange 7 oxidation.
Cobalt-impregnated activated carbon (GAC/Co) was used to produce sulfate radical (SO4·-) from peroxymonosulfate (PMS) in aqueous solution (hereafter called PMS activation). We evaluated its effectiveness by examining the degradation of orange acid 7 (AO7). GAC/Co exhibited high activity to activate PMS to degrade AO7. The degradation efficiency of AO7 increased with increasing dosage of GAC/Co or PMS and elevated temperatures. pH 8 was most favorable for the degradation of AO7 by GAC/Co-activated PMS. The radical quenching experiments indicated that the reactions most likely took place both in the bulk solution and on the surface of GAC/Co. We found that SO4·- played a dominant role in AO7 degradation. Sodium chloride (NaCl) which presents in most dye wastewater had a significant impact on AO7 degradation. Low dosages (<0.4 M) of NaCl showed a slight inhibitory effect, whereas high dosages (0.8 M) increased the reaction rate. HOCl was confirmed as the main contributor for accelerating AO7 degradation with high concentration of NaCl. In a continuous-flow reaction with an empty-bed contact time of 1.35 min, AO7 was not detected in the effluent for 0 to 18.72 L of treated influent volume (156 h) and 85% removal efficiency was still observed after 40.32 L of treated volume (336 h). Finally, the azo bond and the naphthalene structure in AO7 were destroyed and the degradation pathway was proposed.


[Food allergies in early childhood. 1. General concepts, etiopathogenesis, and main clinical features].
Abnormal immune reactions to food antigens are a rather common event during infancy. Adverse reactions to milk proteins occur in 2.5% of suckling infants. Both IgE and non IgE-mediated allergic mechanisms may be involved in the pathogenesis of food allergy. IgE mediated allergic responses are the most dramatic and the most often diagnosed types. Non IgE mediated food allergy is usually more difficult to diagnose and its clinical course is more chronic. Food induced allergic reactions mediate a variety of symptoms, involving the gastrointestinal and respiratory tract and the skin. A limited number of foods are responsible for the vast majority of allergic reactions: cow milk proteins, egg, fish and peanuts are the main causes. The vast majority of infants with formula-protein intolerance will outgrow their symptoms by the third year of age. Eliminating the food allergens is the only means of dealing with the problem. In part I of this series, immunopathogenic mechanisms and clinical disorders are described.


[The indication and effects of palliative right ventricular outflow tract reconstruction for tetralogy of Fallot with pulmonary atresia].
Palliative right ventricular outflow reconstruction (RVOT) in 5 cases with tetralogy of Fallot with valvular pulmonary atresia and 5 cases with truncal pulmonary atresia were studied regarding indication and postoperative development of pulmonary artery. In 4 cases with valvular atresia, RVOT was performed following previous palliation such as Blalock-Taussig shunt, and resulted in improvement in clinical symptoms and in significant increase in postoperative PA-index from 105.4 mm2/m2 before operation to 159.4 mm2/m2. In one case, RVOT was performed as the first stage palliation and symmetrical development of pulmonary arteries were observed. All underwent successful total correction later. However, in 5 cases with the truncal atresia, 2 died after RVOT and postoperative development of pulmonary artery was insignificant. RVOT is indicated for cases with poor pulmonary arterial development despite of palliation, and in future, RVOT as an initial palliation will be indicated in infants with hypoplastic pulmonary artery.


Histone Deacetylase Inhibitors (HDACi) Promote KLF5 Ubiquitination and Degradation in Basal-like Breast Cancer.
Basal-like breast cancer (BLBC) accounts for approximately 15% of all breast cancer cases, and patients with BLBC have a low survival rate. Our previous study demonstrated that the KLF5 transcription factor promotes BLBC cell proliferation and tumor growth. In this study, we demonstrated that the histone deacetylase inhibitors (HDACi), suberoylanilide hydroxamic acid (SAHA), and trichostatin A (TSA), increased KLF5 acetylation at lysine 369 (K369), downregulated KLF5 protein expression levels, and decreased cell viability in BLBC cell lines. HDACi target KLF5 for proteasomal degradation by promoting KLF5 protein ubiquitination. K369 acetylation of KLF5 decreases the binding between KLF5 and its deubiquitinase, BAP1. These findings revealed a novel mechanism by which HDACi suppress BLBC, and a novel crosstalk between KLF5 protein acetylation and ubiquitination.


Prevalence and associated factors of lipohypertrophy in insulin-injected patients with diabetes in selected primary care clinics in Peninsular Malaysian: A cross-sectional study.
This study aimed to determine the prevalence and associated factors of lipohypertrophy in insulin-injecting patients with diabetes at selected primary care clinics in Malaysia. This cross-sectional study was conducted among adults aged ≥18 years with type 1 or 2 diabetes treated with insulin for at least 6 months at six selected public primary care clinics in Malaysia. The Injection Technique Questionnaire was used, and physical examination was conducted to detect the presence of lipohypertrophy. Univariate and multivariate logistic regression analyses were conducted using IBM SPSS version 26. A total of 506 patients with type 2 diabetes were included in this study; of them, 60.47% were women, and 48.42% were Malays. The prevalence of lipohypertrophy was 39.6% (95% Confidence Interval, CI =35%-44%). The univariate analysis revealed that a larger number of injections per day, longer needle length, repeated use of needles, incorrect rotation of the injection site, longer insulin use duration, higher total insulin dose and higher HbA1c level were significantly associated with lipohypertrophy. In the multivariate logistic regression analysis, incorrect rotation of the injection site was the only independent associated factor of lipohypertrophy. The prevalence of lipohypertrophy in this study is comparable with that in other studies. The identified associated factors of lipohypertrophy must be addressed in ongoing health education for insulin-injecting patients at Malaysian primary care clinics. Educating healthcare professionals and increasing awareness among patients with diabetes are important steps in preventing this complication.


Psychosocial stress and impaired sleep.
This review demonstrates that stress is closely related to impaired sleep in cross-sectional studies. In particular, the anticipation of high demands or effort the next day seems important. Sleep recordings show that stress is associated with shortened sleep, fragmentation, and possibly a reduction in sleep stages 3 and 4. Shortened or disturbed sleep causes increases in levels of traditional stress markers (eg, cortisol) and may thus exacerbate the effects of stress. Much knowledge is still lacking, however, particularly about the effects of real-life work stress. The latter requires longitudinal studies in real-life situations.


New serine-derived gemini surfactants as gene delivery systems.
Gemini surfactants have been extensively used for in vitro gene delivery. Amino acid-derived gemini surfactants combine the special aggregation properties characteristic of the gemini surfactants with high biocompatibility and biodegradability. In this work, novel serine-derived gemini surfactants, differing in alkyl chain lengths and in the linker group bridging the spacer to the headgroups (amine, amide and ester), were evaluated for their ability to mediate gene delivery either per se or in combination with helper lipids. Gemini surfactant-based DNA complexes were characterized in terms of hydrodynamic diameter, surface charge, stability in aqueous buffer and ability to protect DNA. Efficient formulations, able to transfect up to 50% of the cells without causing toxicity, were found at very low surfactant/DNA charge ratios (1/1-2/1). The most efficient complexes presented sizes suitable for intravenous administration and negative surface charge, a feature known to preclude potentially adverse interactions with serum components. This work brings forward a new family of gemini surfactants with great potential as gene delivery systems.


Musicogenic epilepsy with ictal asystole: a video-EEG case report.
Musicogenic seizures and ictal asystole are two rare features mainly encountered in temporal lobe epilepsy. We present the first case of musicogenic epilepsy with ictal asystole in a patient with right temporal lobe epilepsy, confirmed by video-EEG. The pathophysiological mechanism of both conditions remains uncertain. These two features appeared after many years of epilepsy in our patient, and although this association might be coincidental, common mechanisms could be involved, including remodelling of neural connections or seizure propagation to a singular zone. This case also highlights the need for precise electroclinical assessment of seizures that change clinically over time, particularly when falls occur after a certain period of latency, suggesting cardiac consequences of the seizures.


Multi-segmented piezoelectric mirrors as active/adaptive optics components.
The angular acceptance of piezoelectric (Pzt) bimorph mirrors is limited by the maximum length of commercially available Pzt ceramic plates. To overcome this limit and manufacture longer devices, several (2n + 1) 150 mm-long bimorph Pzt stacks were assembled side-to-side. Two prototype mirrors, 450 (n = 1) and 750 (n = 2) mm long, were designed, assembled, polished and optically characterized. They are fully UHV compatible and are now installed in the monochromatic section of the ESRF beamlines ID26 and ID32. Both mirrors cover the full range of required bending radii (1 km concave-3.5 km convex). Junctions between segments do not spoil the optical surface quality. The surface slope error r.m.s. can be kept well below 1 arcsec over the full bending range. Adaptive compensation for low-frequency figure errors was shown to be easy and reliable. After compensation, residual shape errors are of the order of 40 nm r.m.s. over 700 mm.


[Intubating laryngeal tube suction disposable: Initial clinical experiences with a novel device for endotracheal intubation].
According to the recent guidelines supraglottic airways, such as laryngeal tubes are recommended to ensure oxygenation in patients with unexpected difficult airways. The novel Intubating Laryngeal Tube Suction Disposable (iLTS-D) is a modified laryngeal tube designed for secondary tracheal intubation. This pilot study evaluated the use of the iLTS-D in clinical practice with respect to practicality and efficacy. In this study the airways of 30 consecutive adult patients with no evidence of a difficult airway undergoing elective ear, nose and throat (ENT) surgery were managed with the iLTS-D. After induction of anesthesia the iLTS-D was placed in position and checked for correct ventilation. Following muscle relaxation, endotracheal intubation through the iLTS-D was performed under continuous visualization using a flexible bronchoscope. Finally, the iLTS-D was removed leaving the endotracheal tube in place. Data were collected anonymously as part of a quality assurance program. Publication of the data was approved by the institutional review board. Initial iLTS-D placement took a median of 17 s (range 12-90 s) and provided sufficient ventilation in all patients; however, the position of the iLTS-D needed to be adjusted in four patients. Endotracheal intubation through the iLTS-D was achieved in 29 out of 30 patients at the first attempt (n = 23) or after 2 attempts (n = 6) and the median time required for intubation was 32 s (range 18-187 s). In five patients no laryngeal structures could initially be identified by bronchoscopy. Blind endotracheal intubation through the iLTS-D was performed in two cases and in two other patients the endotracheal tube was also blindly advanced but into the esophagus. After removal of the endotracheal tube and repositioning of the iLTS-D, successful tracheal intubation was subsequently achieved under bronchoscopic vision. The procedure was aborted and uneventful conventional intubation using direct laryngoscopy was carried out in one patient. The median time for removal of the iLTS-D after successful intubation was 20 s (range 15-80 s). Minor blood stains on the iLTS-D were observed in three patients. With one exception, all problems and adverse events occurred during the first 10 patients. This first clinical study demonstrated that in patients with apparently normal airways and in the hands of users without previous experience, the iLTS-D allowed sufficient ventilation in all patients and had a high success rate for subsequent endotracheal intubation. The results are, however, preliminary until confirmed by further studies, particularly in patients with difficult airways.


Estrogens and aspects of prostate disease.
Estrogens have long been associated with the processes involved in prostate carcinogenesis, particularly in cancer suppression. However, the synergistic influence of low concentrations of estrogens, together with androgens, in promoting aberrant growth of the gland has also been recognized. As new insights into the complex molecular events implicated in growth regulation of the prostate are revealed, the role of the estrogens has become clearer. The present review considers this role in relation to the pathogenesis of prostate cancer and the potential cancer-repressive influence of the dietary estrogens.


Enteroinvasive and enterotoxigenic Escherichia coli. Occurrence in acute diarrhea of infants and children.
The abilities of Escherichia coli to induce diarrhea by enterotoxin production and by intestinal cell penetration have not been explored simultaneously in children with diarrheal disease. In this study, we investigated 36 infants and children with acute diarrhea and 17 healthy controls. From each patient's rectal swab culture, E coli colonies were tested for enterotoxin production by intragastric inoculation in suckling mice and screened for cell penetration with HEp-2 cells. Colonies showing invasiveness in HEp-2 cells were further tested by inoculation into guinea pig conjunctivae. Salmonella or Shigella strains were isolated from 42% of the patients with diarrhea. Enterotoxin-producing strains of E coli were found in 86% of the diarrhea group and in 41% of controls. Strains with capability to invade epithelial cells were found in 30% of the diarrhea group and in 12% of controls. In seven patients, E coli strains demonstrated both enterotoxin production and invasiveness. In an overall view, considering Salmonella, Shigella, and enteroinvasive or enterotoxigenic E coli, a possible etiologic agent was demonstrated in 94% of infants with diarrheal disease. However, the high frequency of enterotoxigenic strains in healthy controls suggest that in some patients with diarrhea there may be a coincidental carrier state with diarrhea actually due to another cause.


Statistical media design for efficient polyhydroxyalkanoate production in Pseudomonas sp. MNNG-S.
Polyhydroxyalkanoate (PHA) is a promising polymer for various biomedical applications. There is a high need to improve the production rate to achieve end use. When a cost-effective production was carried out with cheaper agricultural residues like molasses, traces of toxins were incorporated into the polymer, which makes it unfit for biomedical applications. On the other hand, there is an increase in the popularity of using chemically defined media for the production of compounds with biomedical applications. However, these media do not exhibit favorable characteristics such as efficient utilization at large scale compared to complex media. This article aims to determine the specific nutritional requirement of Pseudomonas sp. MNNG-S for efficient production of polyhydroxyalkanoate. Response surface methodology (RSM) was used in this study to statistically design for PHA production based on the interactive effect of five significant variables (sucrose; potassium dihydrogen phosphate; ammonium sulfate; magnesium sulfate; trace elements). The interactive effects of sucrose with ammonium sulfate, ammonium sulfate with combined potassium phosphate, and trace element with magnesium sulfate were found to be significant (p < .001). The optimization approach adapted in this study increased the PHA production more than fourfold (from 0.85 g L(-1) to 4.56 g L(-1)).


[Application and research progress of bio-derived hydrogels in tissue engineering].
To review the properties of bio-derived hydrogels and their application and research progress in tissue engineering. The literature concerning the biol-derived hydrogels was extensively reviewed and analyzed. Bio-derived hydrogels can be divided into single-component hydro gels (collagen, hyaluronic acid, chitosan, alginate, silk fibroin, etc.) and multi-component hydrogels [Matrigel, the extract of extracellular matrix (ECM), and decellularized ECM]. They have favorable biocompatibility and bioactivity because they are mostly extracted from the ECM of biological tissue. Among them, hydrogels derived from decellularized ECM, whose composition and structure are more in line with the requirements of bionics, have incomparable advantages and prospects. This kind of scaffold is the closest to the natural environment of the cell growth. Bio-derived hydrogels have been widely used in tissue engineering research. Although there still exist many problems, such as the poor mechanical properties, rapid degradation, the immunogenicity or safety, vascularization, sterilization methods, and so on, with the deep-going study of optimization mechanism, desirable bioderived hydrogels could be obtained, and thus be applied to clinical application.


Surgical femorocaval bypass for treating chronic iliac vein occlusion: a case report.
Chronic inferior vena cava and iliac vein occlusion, caused by long-term of deep venous thrombosis, will lead to swelling of the limbs, venous claudication and intractable ulcer. However, conservative treatment is often ineffective for vein occlusion. With the development of interventional techniques, endovascular therapy has become the first choice for the treatment of vein occlusion with higher success rate and lower trauma. However, for cases those fail endovascular therapy or for segmental veno-occlusive diseases with low long-term patency rate, venous bypass might be the only option. And, design of anastomotic stoma and orificium fistulae design is crucial to the success of operation. A case of long term deep venous thrombosis patient with occlusion in bilateral iliac vein and distal inferior vena cava was admitted and treated with interventional therapy. Unfortunately, this method failed. Then, we selected reasonable anastomotic stoma and orificium fistulae and performed femorocaval bypass. The 12 month follow-up results showed that the swelling was successively relieved and the ulcer healed. This indicated that rational anastomotic stoma and orificium fistulae could guarantee the exact clinical efficacy of venous bypass and higher long-term patency rate.