Evaluation and management of "functional" nasolacrimal blockage: results of a survey of the American Society of Ophthalmic Plastic and Reconstructive surgery.
A survey was mailed to members of The American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) concerning the diagnosis and management of patients with epiphora. Specifically, the respondent was asked about his or her work-up and management of an older patient with epiphora whose nasolacrimal system was patent on irrigation. Some pertinent findings were that 48 respondents did not choose the Jones test as one of the diagnostic procedures they employ. A small percentage of respondents do only a Jones test in their evaluation and believe that a dacryocystorhinostomy (DCR) is indicated with a negative Jones test. Technetium scan and dacryocystogram are used by only 13 and 10% of respondents, respectively. Forty-one percent of respondents would treat a pump "functional" block with DCR; 25% would use either Silastic tubing, lid tightening, or a combination of both. Most respondents believed that the success rate of Silastic tubing was fair, at best.


In vivo electrophysiological characterization of TASK-1 deficient mice.
TASK-1 is a potassium channel predominantly expressed in heart and brain. We have previously shown that anesthetized TASK-1(-/-)mice have prolonged QT intervals in surface electrocardiograms (ECGs). In addition, heart rate variability quantified by time and frequency domain parameters was significantly altered in TASK-1(-/-) mice with a sympathetic preponderance. Aims of the present study were the analysis of QT intervals by telemetric ECGs, to determine potential influences of anesthesia and β-adrenergic stimulation on repolarization in surface ECGs, to investigate in vivo electrophysiological parameters by intracardiac electrical stimulation and to quantify heart rate turbulence after ischemia/reperfusion or ventricular pacing in TASK-1(+/+) and TASK-1(-/-) mice. Rate corrected QT intervals (QTc) were recorded in conscious mice by telemetry and in surface ECGs following administration of various anesthetics (tribromoethanol (Avertin(®)), pentobarbital and isoflurane). TASK-1(+/+) and TASK-1(-/-) mice were characterized by programmed electrical stimulation using an intracardiac octapolar catheter. The baroreceptor reflex was analyzed by heart rate turbulence (turbulence onset and slope) after ischemia/reperfusion and by stimulated premature ventricular contractions. Telemetric and surface ECGs in mice sedated with Avertin(®) and pentobarbital, showed a significantly lengthened rate corrected QT interval in TASK-1(-/-) mice (telemetry: TASK-1(+/+) 43±3ms vs. TASK-1(-/-) 49±5ms, n=6, p<0.05; Avertin(®): TASK-1(+/+) 36±8ms vs. TASK-1(-/-) 48±4ms, n=13/16, p<0.0001). The prolongation of the QT interval was most pronounced at lower heart rates. Isoflurane, known for its stimulatory effects on the TASK channel family, attenuated the rate corrected QT interval prolongation in TASK-1(-/-)mice. Intracardiac electrical stimulation revealed normal values for electrical conduction and refractoriness. No significant arrhythmias after atrial and ventricular burst stimulation were induced before and after adrenergic challenge in both genotypes. Turbulence onset after premature ventricular contraction was significantly altered in TASK-1(-/-) mice. TASK-1(-/-) mice exhibit a phenotype of QT prolongation, which distinct relation to heart rate. TASK-1 deficiency does neither alter key electrophysiological parameters nor increases atrial/ventricular vulnerability after electrical stimulation. The heart rate response after premature ventricular contractions is significantly abolished indicating a diminished baroreceptor reflex in TASK-1(-/-) mice.


Death sentences: a content analysis of children's death literature.
A multidimensional concept of death must include biological, sociocultural, and emotional components. Children glean information about death in many ways, one of which is through books. In this study, the authors compared the 3 dimensions of death-related information (irreversibility, inevitability, nonfunctionality) in 24 young children's picture books and 16 older children's storybooks. In these death-themed children's books, the primary focus was on emotional aspects of death and grieving. Biological facts were more likely to appear in picture books than in storybooks. The authors offer speculation on the impact of children's books for use with bereaved children.


The resistance to antimicrobial agents of Staphylococcus aureus isolated from the bovine udder.
Isolates of Staphylococcus aureus (total 1657) from bovine mastitis were collected from 13 laboratories throughout Australia from 1974 to 1979. They were tested for resistance to antimicrobial agents using an agar dilution method. Resistance shown was mainly to penicillin and streptomycin. Occasional strains were resistant to neomycin, lincomycin, erythromycin, tetracycline, chloramphenicol and furazolidone but multiple resistance was rare. No strain showed resistance to methicillin. Resistance to penicillin declined from 35% in 1974-75 to 7.1% in 1979. Most strains (1395) were retested to allow induction of penicillinase; 62% produced the enzyme.


Left ventricular ejection fraction using manual and semi-automated biplane method of discs in very preterm infants.
Biplane left ventricular ejection fraction (LVEF) is a valuable echocardiographic parameter for assessment of LV systolic pump efficiency in adults and children, but not often reported in preterm infants. The primary aim of this study was to longitudinally measure biplane LVEF in very preterm infants during the neonatal intensive care period. Secondary aim was to compare manual and semi-automatic determination of LVEF for agreement and variability. Stable preterm infants less than 30 weeks gestation were scanned on day 3, day 28, and at 36 weeks postmenstrual age. The LV endocardium was traced manually and semi-automatically using integrated speckle tracking software in apical 4-chamber and apical 3-chamber images to obtain end-diastolic volume and end-systolic volume, and calculate LVEF. Agreement between methods and variability within and between observers was determined using an interclass correlation coefficient (ICC) and Bland-Altman analysis. Sixty-six preterm infants with a mean birth weight of 1100 (239) g were analyzed. The average manual biplane LVEF was 58 (3)%, 59 (3)%, and 55 (4)% at the three respective time points. Manual LVEF showed good agreement with semi-automatic LVEF (ICC 0.76) with a small bias of -1.5 (3.0)%. Interobserver variability of LVEF improved with semi-automatic tracing of the LV endocardial border (ICC manual 0.68 vs semi-automatic 0.80). Left ventricular systolic pump efficiency in preterm infants remains stable during the neonatal intensive care period. Semi-automatic biplane LVEF has less interobserver variability and can be used interchangeably with manual biplane LVEF.


Therapeutic links between Alzheimer's disease and brain cancer: drug discovery consequences.
It was recently reported that female survivors of breast cancer have a lower risk of Alzheimer's disease (AD). This observation led to the hypothesis that there is a link between cancer and AD. This Viewpoint provides an analysis of the consequences of this hypothesis, not only from the perspective of drug discovery for new treatments, but above all, the awareness that any AD chemotherapy will require drug administration over longer periods of time before any cognitive effects are observed. Because such drugs will probably act as neuroprotective agents, slowing the progression of AD rather than curing it, they should be prescribed as soon as the first AD symptoms are detected. After a general survey of anticancer drugs that have potential therapeutic value for AD chemotherapy, new drugs that could affect specific signal transduction pathways known to be activated by anticancer drugs are presented, with the unfolding protein response pathway being one of the most relevant biological targets for new AD chemotherapeutic agents.


Authentication of Polygonati Odorati Rhizoma and other two Chinese Materia Medica of the Liliaceae family by pharmacognosy technique with GC-MS analysis.
Yuzhu (Polygonati Odorati Rhizoma), Kangdingyuzhu (Polygonati Prattii Rhizoma), and zhugenqiyuzhu (Disporopsis Fuscopictae Rhizoma) are of the same family, but of different genera. They have all often used in Chinese Materia Medica (CMM) as Polygonati Odorati Rhizoma in China market. Three species of CMM are confused. For better application, we need to identify these plants accurately. This study use pharmacognosy technique and GC-MS analysis, three species of CMM were authenticated. In macroscopic characteristics, the fruit of Polygonati Odorati Rhizoma is blue-black, while the other two are maroon and dark purple orderly. Nodes of Polygonati Odorati Rhizoma are upward and light uplift, about 1 cm spacing, while the other are not. As for microscopic characteristics, the cortex of Polygonati Odorati Rhizoma only occupies about 1/5 of the radius of the transverse section with inconspicuous endodermis, which is much smaller than others. The type of vascular bundles of Polygonati Odorati Rhizoma is closed collateral, but the other is amphivasal. Raphides of calcium oxalate are scattered, but Raphides of the other two are like brooms and neat rows. GC-MS analysis of essential oil could provide different characteristics to distinguish three species. Twenty-three compounds were identified from essential oil of Polygonati Odorati Rhizoma and the main components were n-hexadecanoic acid (49.45%), while n-hexadecanoic acid of the other two are 23.92% and 9.45%. The content of n-hexadecanoic is strongly different. This research was aimed to establish a method by pharmacognosy and GC-MS analysis to identify three CMM and for providing scientifical data to ensure accuracy of origin of three species.


Implications of Virtual CBCT-Based Immediate Implant Planning for Maxillary and Mandibular First Molars.
The purpose of his study was to investigate the projected ridge-implant dimensions derived from virtual superimposition of implants on intact first molars mimicking immediate implantation in the mandible (Md1) and maxilla (Mx1) using cone-beam computed tomography (CBCT). The CBCT records of 41 patients (19 males and 22 females) with Md1 or Mx1 were collected. Ten-millimeter-long cylindrical implants with different diameters were virtually positioned at prosthetically ideal angles into interradicular septum using CBCT software. Radiographic alveolar ridge height (ARH), alveolar ridge width (ARW), gap distance, and vertical distance from the implant platform to the alveolar crest were measured. Twenty Mx1s (48.8%) and 21 Md1s (51.2%) were included. The mean ARH values were 7.13 ± 4.32 and 15.64 ± 1.80 mm for Mx1 and Md1, respectively; 87.8% of mesiobuccal sites had gap distance of >2 mm when 6-mm-diameter implants were used. Increasing implant diameter from 6 to 9 mm decreased the percentage of sites with ARW > 2 mm from 80.5% to 41.5% buccally and from 86.4% to 26.8% lingually. The mean vertical distance from the implant platform to the alveolar crest was 1.41 ± 1.09 mm buccally and 1.11 ± 1.10 mm lingually. Immediate implant placement of first molars, especially in the maxilla, requires stringent presurgical evaluation. Implants no wider than 6 mm placed into the interradicular septum may meet acceptable running room and alveolar plate thickness criteria if the jumping distance is grafted. Further clinical trials are needed to confirm these findings in this virtual study.


Bicarbonate-dependent action of Bay K 8644 in the smooth muscle of the rat vas deferens.
Effects of Bay K 8644, partial depolarization with high potassium, and nifedipine on the dose-response curves of the rat vas deferens to norepinephrine, methacholine and KCI were investigated in HEPES-buffered physiological salt solution (PSS) with or without 20 mM sodium bicarbonate. In the bicarbonate-containing PSS, Bay K 8644 at 10(-6) M enhanced the maximal contractions in response to norepinephrine, methacholine and KCI by 31.4, 103.3 and 40.1%, respectively. In the bicarbonate-free PSS, where the maximal contractions induced by norepinephrine, methacholine and KCI were 77.5, 75.0 and 68.2% of those in the bicarbonate-containing PSS, respectively. Bay K 8644 did not enhance the maximal contractile response to any of the agonists, although the contractions induced by low concentrations of KCI were increased by Bay K 8644. Increasing the potassium concentration in the PSS from 6 to 20 mM enhanced the maximal contractions in response to norepinephrine and methacholine in the bicarbonate-containing PSS, whereas in the bicarbonate-free PSS, the treatment decreased the contractions. In the two PSSs, nifedipine similarly inhibited the contraction in response to either 10(-5) M norepinephrine or 68 mM KCI. These results suggest that bicarbonate ion modulates the function of the voltage-dependent calcium channel in the smooth muscle of the rat vas deferens.


Enarodustat to treat anemia in chronic kidney disease.
Anemia is a common complication in patients with chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs) are the standard therapy for anemia in CKD. It has been expected that hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibition may have the potential to provide therapeutic benefits over pre-existing ESAs for anemia in CKD. Enarodustat (JTZ-951) is an oral HIF-PH inhibitor. In preclinical studies, enarodustat has been found to increase HIF-alpha proteins, erythropoietin production and erythropoiesis. Enarodustat also shows efficient iron utilization in iron-related parameters during erythropoiesis. Clinical trials have shown that enarodustat improved anemia both in non-dialysis-dependent CKD patients and dialysis patients. The safety results in clinical trials demonstrate that enarodustat is generally well tolerated. On the basis of these results, enarodustat was approved in September 2020 in Japan for the treatment of anemia associated with CKD. This manuscript will review enarodustat, its pharmacological characteristics in preclinical studies, and its efficacy and safety in clinical trials with anemic patients in CKD.


Silyl linker-based approach to the solid-phase synthesis of Fmoc glycopeptide thioesters.
An efficient solid-phase synthesis of Fmoc (glyco)peptide thioesters is described. Fmoc x Ser x OAll and Fmoc x Thr x OAll bound to resin with a silyl ether linker were deallylated by Pd(0) catalysis and condensed with thiophenol, benzyl mercaptane, and ethyl 3-mercaptopropionate by activation with DCC/HOBt. The thioesters were released from the resin either by treatment with CsF-AcOH or by acidic hydrolysis. The effectiveness of this silyl linker strategy is further demonstrated by the synthesis of more complex (glyco)peptide thioesters 25, 26 and 27 involving N-->C and C-->N peptide elongation.


Is retinal vein occlusion associated with depression symptoms?: A nationwide cohort study.
Retinal vessels share similar anatomical and physiological characteristics with the cerebral microvasculature, and abnormal cerebral blood flow is reportedly associated with depressive disorder. However, there is limited evidence regarding the relationship between depression and the risk of retinal vein occlusion (RVO). This study aimed to investigate the association between depression and the prospective risk of RVO using nationally representative longitudinal data. This retrospective, nationwide, population-based cohort study included 9,178,222 people aged 20 years or older who underwent the Korean National Health Screening Program examination in 2009. The depression group consisted of subjects whose initial diagnoses were made between 2009 and 2010 (n = 128,700). The predictive value for RVO was analyzed using multivariate Cox proportional hazard regression models.From the Kaplan-Meier curves, the depression group showed significantly higher RVO incidence probability, relative to the comparison group (P < .0001). After all confounding variables were adjusted, the hazard ratio of RVO in the depression group with or without recurrence was 1.2 (95% confidence interval [CI]: 1.076-1.338) and 1.087 (95% CI: 1.012-1.167), respectively, relative to the comparison group. This is the first nationwide, population-based, epidemiologic study that evaluated the association between depression and the risk of RVO development. The presence of depression was significantly associated with increased risks of RVO, and the recurrence of depression showed a higher RVO incidence probability.


Histologic and histomorphometric analysis of an immediately loaded implant retrieved from man after 14 months of loading.
The aim of this study was a histologic and histomorphometric analysis of the peri-implant tissue reactions and the bone/titanium interface in an immediately loaded titanium implant inserted in a soft bone site and retrieved, in man, after a 14-month loading period. METHODS. A 65-year-old patient presented with a partial edentulism in the left posterior mandible. The patient was rehabilitated with three dental implants inserted in the left first, second, and third molar sites. All these implants were immediately put into a nonfunctional loading mode and joined with the other implants that supported the temporary restorations. After 14 months, the most distal implant and surrounding tissues were retrieved because of psychological problems of the patient. Newly formed, strongly stained, compact, mature cortical bone with few marrow spaces was observed around the implant, especially in the coronal portion. No inflammatory infiltrate was present around the implant. No gaps or dense fibrous connective tissue were found at the bone/metal interface. No apical epithelial migration was found. In the cortical portion, bone remodeling areas were present with many newly formed Haversian canals. Only in a few areas of the interface was it possible to observe an osteoblast rim. In the apical portion, newly formed bone trabeculae were present; these were composed mostly by woven bone, and only a small quantity of preexisting lamellar bone was present. Histomorphometric evaluation showed that the bone/implant contact percentage was 72.6% (+/-2.7%). We found that, in immediately loaded implants inserted in soft tissue sites, it was possible to find a high percentage of bone-to-implant contact and that osseointegration was maintained for more than 1 year. This fact could be partly explained with the use of an implant with a rough surface.


Moles, melanomas and epitheliomas in children.
The management of moles which occur in childhood is important from the standpoint of clinical diagnosis and treatment. Melanomas of both the malignant and juvenile types are sometimes mistaken for ordinary moles. Malignant epithelial tumors are rare in childhood as are congenital tumors. There is a possible relationship between congenital defects of various types and childhood neoplasms.


The structure of T6 bovine insulin.
Porcine insulin differs in sequence from bovine insulin at residues A8 (Thr in porcine-->Ala in bovine) and A10 (Ile in porcine-->Val in bovine). The structure of T6 hexameric bovine insulin has been determined to 2.25 A resolution at room temperature and refined to a residual of 0.162. The structure of the independent dimer is nearly identical to the T6 porcine insulin dimer: the mean displacement of all backbone atoms is 0.16 A, with the largest displacements occurring at AlaB30. Each of two independent zinc ions is octahedrally coordinated by three HisB10 side chains and three water molecules. As has been observed in both human and porcine insulin, the GluB13 side chains are directed towards the center of the hexamer, where a short contact of 2.57 A occurs between two independent carboxyl O atoms, again suggesting the presence of a centered hydrogen bond. No significant displacements of backbone atoms or changes in conformation are observed at A8 or A10. Since there are no interhexamer hydrogen-bonded contacts involving A8 in either porcine or bovine insulin, the change in the identity of this residue appears to have little or no effect upon the packing of the hexamers in the unit cell. In contrast, the side chains of the three A10 residues in one trimer make van der Waals contacts with the A10 side chains in a translationally related hexamer. As a consequence of the loss of the C(delta1) atom from the isoleucine residue in porcine insulin to produce valine in bovine insulin, there is a 0.36 A decrease in the distance between independent pairs of C(beta) atoms and a 0.24 A decrease in the c dimension of the unit cell. Thus, the net effect of the change in sequence at A10 is to strengthen the stabilizing hydrophobic interactions between hexamers.


Association between corticosteroid therapy and diagnosis of non-traumatic rotator cuff tear or rupture in patients followed in orthopedic practices in Germany.
The purpose of this case-control study was to examine the association between oral and injected corticosteroids (CS) and subsequent non-traumatic rotator cuff tear or rupture (nt RCT or RCR) in orthopedic practices in Germany. Patients diagnosed with nt RCT or RCR between January 2017 and December 2019 (index date) were included in the study after applying inclusion and exclusion criteria. Controls without nt RCT or RCR were matched using propensity scores based on age, sex, observation time prior to the index date (years), and diseases of the musculoskeletal system and connective tissue. A total of 10,986 patients were included in each group. For both oral and injected CS, we found a significant association with nt RCT or RCR, whereby oral CS had a stronger impact (OR (oral): 1.71 (95% CI: 1.52 - 1.93) vs. OR (injected): 1.42 (95% CI: 1.28 - 1.58)). For oral CS, this association was largely unaffected by differences in total doses or latencies between therapy end and index date. Within the group who received injected CS, shorter latencies and total doses of 20 mg or more led to higher odds of nt RCT or RCR. Varying CS had a different impact on rotator cuff tendons. Non-steroidal anti-inflammatory drugs (NSAIDs) were not associated with nt RCT or RCR at all. Oral and injected CS were associated with nt RCT or RCR in patients treated in orthopedic practices in Germany, while analgesics such as NSAIDs were not.


Functional interaction of fibroblast growth factor 8b and androgen in prostate cancer cell proliferation.
Fibroblast growth factor 8b and androgen play important roles in cell proliferation of prostate cancer. We investigated the effects of fibroblast growth factor 8b and androgen on the proliferation of prostate cell lines and the corresponding intracellular mechanisms. It is found that dihydrotestosterone and fibroblast growth factor 8b stimulated Lncap cell mitosis in a concentration-responsive manner, with 30 ng/mL as the most suitable concentration, respectively. Dihydrotestosterone treatment alone did not enhance the expression and phosphorylation level of fibroblast growth factor receptor but significantly enhanced the level of fibroblast growth factor receptor phosphorylation elicited by fibroblast growth factor 8b. Phosphorylations of extracellular signal-regulated kinase, p38, and c-Jun NH2-terminal kinase were stimulated by dihydrotestosterone or fibroblast growth factor 8b. Among these major downstream pathways for mitogen-activated protein kinase, c-Jun NH2-terminal kinase signaling was most significantly enhanced. Protein kinase C phosphorylation was higher than AKT by the combined stimulation of dihydrotestosterone and fibroblast growth factor 8b. The phosphorylation of CDC2 was significantly induced by dihydrotestosterone and fibroblast growth factor 8b synergetically, and Smad underwent the same induction as CDC2. So the promoting effect of fibroblast growth factor 8b on cell cycle might contribute to the G2/M transition. This study indicated that the functional interaction between fibroblast growth factor 8b and androgen was essential for the prostate cancer cell proliferation.


Motor adaptation and generalization of reaching movements using motor primitives based on spatial coordinates.
The brain processes sensory and motor information in a wide range of coordinate systems, ranging from retinal coordinates in vision to body-centered coordinates in areas that control musculature. Here we focus on the coordinate system used in the motor cortex to guide actions and examine physiological and psychophysical evidence for an allocentric reference frame based on spatial coordinates. When the equations of motion governing reaching dynamics are expressed as spatial vectors, each term is a vector cross product between a limb-segment position and a velocity or acceleration. We extend this computational framework to motor adaptation, in which the cross-product terms form adaptive bases for canceling imposed perturbations. Coefficients of the velocity- and acceleration-dependent cross products are assumed to undergo plastic changes to compensate the force-field or visuomotor perturbations. Consistent with experimental findings, each of the cross products had a distinct reference frame, which predicted how an acquired remapping generalized to untrained location in the workspace. In response to force field or visual rotation, mainly the coefficients of the velocity- or acceleration-dependent cross products adapted, leading to transfer in an intrinsic or extrinsic reference frame, respectively. The model further predicted that remapping of visuomotor rotation should under- or overgeneralize in a distal or proximal workspace. The cross-product bases can explain the distinct patterns of generalization in visuomotor and force-field adaptation in a unified way, showing that kinematic and dynamic motor adaptation need not arise through separate neural substrates.


Identifying novel genes in C. elegans using SAGE tags.
Despite extensive efforts devoted to predicting protein-coding genes in genome sequences, many bona fide genes have not been found and many existing gene models are not accurate in all sequenced eukaryote genomes. This situation is partly explained by the fact that gene prediction programs have been developed based on our incomplete understanding of gene feature information such as splicing and promoter characteristics. Additionally, full-length cDNAs of many genes and their isoforms are hard to obtain due to their low level or rare expression. In order to obtain full-length sequences of all protein-coding genes, alternative approaches are required. In this project, we have developed a method of reconstructing full-length cDNA sequences based on short expressed sequence tags which is called sequence tag-based amplification of cDNA ends (STACE). Expressed tags are used as anchors for retrieving full-length transcripts in two rounds of PCR amplification. We have demonstrated the application of STACE in reconstructing full-length cDNA sequences using expressed tags mined in an array of serial analysis of gene expression (SAGE) of C. elegans cDNA libraries. We have successfully applied STACE to recover sequence information for 12 genes, for two of which we found isoforms. STACE was used to successfully recover full-length cDNA sequences for seven of these genes. The STACE method can be used to effectively reconstruct full-length cDNA sequences of genes that are under-represented in cDNA sequencing projects and have been missed by existing gene prediction methods, but their existence has been suggested by short sequence tags such as SAGE tags.


Nutritional, pharmaceutical, and functional aspects of rambutan in industrial perspective: An updated review.
Numerous researchers have been motivated to investigate new plant sources as a result of the continued advancement of functional foods and herbal medicines. The rambutan fruit (Nephelium lappaceum L.) with its significant nutritional and bioactive compositions offers therapeutic properties such as anticancer, antiallergic, antiobesity, antidiabetic, antimicrobial, antihypercholesterolemic, and antihyperglycemic. Rambutan is high in antioxidants, dietary fibers, and vitamins and minerals. Its parts including fruit peel, pulp, and seed are a great source of bioactive compounds. Rambutan fruit extracts have been found to have cardioprotective and hepatoprotective properties. This review provides an insight into the nutritional as well as therapeutic value, health potential, and utilization of rambutan fruit along with its nonedible parts (seeds and peels). Advanced research and phytochemical screening would also encourage the rambutan fruit as a viable choice for the preparation of medications and functional foods. However, it is necessary to further analyze the functional aspects and nutritional potential of this fruit along with the therapeutic mechanisms and to improve its industrial use as a nutraceutical and functional food product.


cDNA analysis of gene expression associated with DNA-dependent protein kinase activity.
DNA-dependent protein kinase (DNA-PK) is thought to play a pivotal role in DNA double-strand break repair. We recently demonstrated the association of DNA-PK activity in peripheral blood lymphocytes (PBL) with the incidence of chromosomal aberrations and the risk of cancer. In this study, we applied cDNA array technology to find the expression of genes which are associated with DNA-PK activity in PBLs with various levels of DNA-PK activity. Most genes correlated with DNA-PK activity involved cell cycle regulation. Moreover, the transcription factor E2F1, which plays an important role in cell cycle progression, exhibited strong correlation with the DNA-PK activity and Rbp130, which is considered a negative regulator of E2F, showed inverse correlation with DNA-PK activity. In silico promoter analyses showed the presence of at least one E2F binding site in the promoter regions of Ku70, Ku86, DNA-PKcs and genes associated with DNA-PK activity. In order to examine the relationship among the E2F1 expression, the expression of genes related with DNA-PK activity, and DNA-PK activity, we activated PMLs by PHA to progress the cell cycle. After PHA activation of PML, the expression of E2F1 and DNA-PK activity increased. The expression of most genes in PHA-stimulated PBLs had a similar relationship with DNA-PK activity to that without PHA stimulation. These results indicate that the E2F transcription factor may regulate the concerted expression of genes related with DNA-PK activity.


Radiological spectrum of anthracofibrosis: A series of 40 patients with computed tomography, bronchoscopy, and biopsy.
Anthracofibrosis is a lesser known clinical entity. Patients present with chronic symptoms of cough and breathlessness with a history of biofuel/wood fire smoke exposure. There are distinct computed tomography (CT) imaging features of anthracofibrosis that can differentiate it from more common conditions such as tuberculosis (TB) and bronchogenic carcinoma. Findings include multifocal noncontiguous stenosis of bronchial tree, calcified enlarged mediastinal or hilar nodes, and secondary lung parenchymal changes. However, in TB, bronchostenosis usually involves a single lobar bronchus in a contiguous manner with trachea and/or major bronchi also being affected. In this study, we highlight the imaging characteristics of anthracofibrosis. The CT findings of anthracofibrosis closely mimic TB and bronchogenic carcinoma, hence we highlight the key imaging features of anthracofibrosis. To identify and describe the CT imaging features of anthracofibrosis and correlate it with bronchoscopic findings. Retrospective study. Retrospectively, 40 patients were selected who were diagnosed with anthracofibrosis on bronchoscopy and biopsy. However, CT scan records of only 14 patients were available for review. Two radiologists reviewed the scans independently. Most common CT finding was multisegmental noncontiguous bronchostenosis seen in 93% patients mostly involving the right middle lobe. 85% of the cases showed lymph node enlargement involving hilar, peribronchial, and mediastinal nodes. The nodes were calcified in 91.7% of the cases, with 58% showing pressure effect on adjacent bronchi due to nodal enlargement. The next common findings were peribronchial cuffing and bronchial obstruction seen in 57 and 28% of the cases, respectively. The key imaging features of anthracofibrosis on CT are multifocal involvement of bronchi with smooth peribronchial thickening and enlarged calcified lymph nodes.


Experimental infection of Paragonimus westermani in mice and rats.
To determine the infectivity and maturity of metacercariae of Paragonimus westermani after keeping at low temperature for a long period, 45 mice and 45 rats were each infected with 20 metacercariae which were kept at 4 degrees C for 8 to 234 days. The worm recovery in mice increased with age of worm and reached a peak of 32% at 41-50 days and then decreased with age. The rate in rats first decreased to a lowest point of 6% at 71-100 days and then increased with age. In 42 infected mice and 41 infected rats, 187 immature worms (183 tiny and 4 juvenile ones) and 190 worms (164 tiny, 19 juvenile and 7 mature ones) were recovered respectively. Two worm cysts with eggs only and 8 empty worm cysts were also found in the rats. In addition, the frozen metacercariae can still develop to mature worms in SD rats.


Infrared spectral marker bands characterizing a transient water wire inside a hydrophobic membrane protein.
Proton conduction along protein-bound "water wires" is an essential feature in membrane proteins. Here, we analyze in detail a transient water wire, which conducts protons via a hydrophobic barrier within a membrane protein to create a proton gradient. It is formed only for a millisecond out of three water molecules distributed at inactive positions in a polar environment in the ground state. The movement into a hydrophobic environment causes characteristic shifts of the water bands reflecting their different chemical properties. These band shifts are identified by time-resolved Fourier Transform Infrared difference spectroscopy and analyzed by biomolecular Quantum Mechanical/Molecular Mechanical simulations. A non-hydrogen bonded ("dangling") O-H stretching vibration band and a broad continuum absorbance caused by a combined vibration along the water wire are identified as characteristic marker bands of such water wires in a hydrophobic environment. The results provide a basic understanding of water wires in hydrophobic environments.


Suspension Array of Ionic Liquid or Ionic Liquid-Quantum Dots Conjugates for the Discrimination of Proteins and Bacteria.
It is of great importance to develop novel and sensitive sensing materials for the detection of proteins and microorganisms to fulfill the demand of disease diagnosis. As the selectivity and sensitivity of sensing systems are highly dependent on the receptor, the fluorescent sensor array with imidazolium ionic liquids (ILs) and ionic liquid-quantum dots conjugates as semiselective receptors is developed for protein/bacteria differential sensing or discrimination. The IL sensing system formed by 1,3-dibutylimidazolium chloride (BBimCl), 1,3-diethylimidazolium bromine (EEimBr), 1,3-dibutylimidazolium bromine (BBimBr), 1,3-dihexylimidazolium bromine (HHimBr), and 1,3-dioctylimidazolium bromine (OOimBr) and the IL@QDs/QDs sensing system formed by CdTe, BBimCl@CdTe, EEimBr@CdTe, BBimBr@CdTe, and HHimBr@CdTe are tested, by transferring the interaction binding difference between receptors and proteins to the fluorescent response pattern. The IL sensing system is applied to the identification of 48 samples (8 proteins at 500 nM) with an accuracy of 91.7%. For the IL@QDs/QDs sensing system, 8 proteins are completely distinguished with 100% accuracy at a very low concentration level of 10 nM. Remarkably, 36 training cases (6 strains of bacteria from 3 different species) are discriminated with 100% (OD600 of 0.1).


Serum IgE Levels Are Associated With the Prognosis of Minimal Change Disease.
Previous reports showed that some patients with minimal change disease (MCD) had high serum immunoglobulin E (IgE) levels. This study aimed to explore the proportion of MCD patients with high serum IgE levels and evaluate the correlation between serum IgE levels and MCD remission and relapse. This study enrolled 222 new-onset patients with renal biopsy-confirmed MCD from October 2012 to October 2019 at the First Affiliated Hospital of Zhejiang University in Hangzhou, China. Patients' demographics and clinical parameters were analyzed. The results indicated that 70.3% of 222 MCD patients had high serum IgE levels (IgE > 100.0 IU/mL). Moreover, 134 patients were treated with glucocorticoids alone and divided into the low- and high-IgE groups, according to the median serum IgE level (523.5 IU/mL). The mean time to complete remission of the low- and high-IgE groups was 29.0 ± 2.2 and 45.7 ± 4.2 days, respectively (log-rank test; P = 0.002). The mean time to total remission was 19.1 ± 1.4 and 31.6 ± 3.2 days of the low- and high-IgE groups, respectively (log-rank test; P < 0.001). The mean time to first relapse in the low- and high-IgE groups was 701.2 ± 65.0 and 425.0 ± 52.6 days, respectively (log-rank test; P = 0.002). Serum IgE ≥ 523.5 IU/mL was an independent correlation factor affecting the patients' remission and relapse. Serum IgE level was an independent correlation factor for MCD remission and relapse. MCD patients with high serum IgE levels were prone to delayed remissions and early relapses.


PHOXI: A High Quantum Yield, Solvent-Sensitive Blue Fluorescent 5-Hydroxytryptophan Derivative Synthesized within Ten Minutes under Aqueous, Ambient Conditions.
Multiple tryptophan (Trp) proteins are not amenable to fluorescence study because individual residue emission is not resolvable. Biosynthetic incorporation of an indole analogue such as 5-hydroxyindole has not provided sufficient spectroscopic resolution because of low quantum yield and small emission shift. Here, 5-hydroxyindole is used as the starting framework for building a blue emitting fluorophore of high quantum yield, 2-phenyl-6H-oxazolo[4,5-e]indole (PHOXI). This is a three reagent reaction completed in 10 min under ambient conditions in borate buffer at pH 8. Reaction conditions have been optimized using 5-hydroxyindole. Derivatization is demonstrated on tryptophanyl 5-hydroxytryptophan (5-HTP) and a stable β-hairpin "zipper" peptide with four tryptophan residues, TrpZip2, where Trp 4 has been replaced with 5-HTP, W4 → 5-HTP. Reaction optimization yields a PHOXI fluorophore that is essentially free of byproducts. Reaction specificity is demonstrated by the lack of reaction with N-acetyl-cysteine and amyloid β-40, a peptide containing all amino acids except tryptophan, proline, and cysteine and lacking 5-HTP. Fluorescence study of PHOXI-derivatized 5-hydroxyindole in different solvents reveals the sensitivity of PHOXI to solvent polarity with a remarkable 87 nm red-shift in water relative to cyclohexane while maintaining high quantum yield. Thus, PHOXI joins the ranks of solvatochromic fluorophores such as PRODAN. Surprisingly, DFT calculations reveal coplanarity of the oxazolo/indole extended ring system and the phenyl substituent for both the HOMO and LUMO orbitals. Despite the crowded environment of three additional Trps in TrpZip2, CD spectroscopy shows that the TrpZip2 β-hairpin structure is partially retained upon PHOXI incorporation. In an environment of smaller residues, PHOXI incorporation can be less disruptive of protein secondary structure, especially at molecular interfaces and other environments where there is typically less steric hindrance.


Can Free Water Transport Be Used as a Clinical Parameter for Peritoneal Fibrosis in Long-Term PD Patients?
Sodium sieving in peritoneal dialysis (PD) occurs in a situation with high osmotically-driven ultrafiltration rates. This dilutional phenomenon is caused by free water transport through the water channel aquaporin-1. It has recently been described that encapsulating peritoneal fibrosis is associated with impaired free water transport, despite normal expression of aquaporin-1. In this review, it will be argued that free water transport can be used for assessment of fibrotic peritoneal alterations, due to the water-binding capacity of collagen. Finally, the consequences for clinical practice will be discussed.


'Lumbar Degenerative Kyphosis' Is Not Byword for Degenerative Sagittal Imbalance: Time to Replace a Misconception.
Lumbar degenerative kyphosis (LDK) is a subgroup of the flat-back syndrome and is most commonly caused by unique life styles, such as a prolonged crouched posture during agricultural work and performing activities of daily living on the floor. Unfortunately, LDK has been used as a byword for degenerative sagittal imbalance, and this sometimes causes confusion. The aim of this review was to evaluate the exact territory of LDK, and to introduce another appropriate term for degenerative sagittal deformity. Unlike what its name suggests, LDK does not only include sagittal balance disorder of the lumbar spine and kyphosis, but also sagittal balance disorder of the whole spine and little lordosis of the lumbar spine. Moreover, this disease is closely related to the occupation of female farmers and an outdated Asian life style. These reasons necessitate a change in the nomenclature of this disorder to prevent misunderstanding. We suggest the name "primary degenerative sagittal imbalance" (PDSI), which encompasses degenerative sagittal misalignments of unknown origin in the whole spine in older-age patients, and is associated with back muscle wasting. LDK may be regarded as a subgroup of PDSI related to an occupation in agriculture. Conservative treatments such as exercise and physiotherapy are recommended as first-line treatments for patients with PDSI, and surgical treatment is considered only if conservative treatments failed. The measurement of spinopelvic parameters for sagittal balance is important prior to deformity corrective surgery. LDK can be considered a subtype of PDSI that is more likely to occur in female farmers, and hence the use of LDK as a global term for all degenerative sagittal imbalance disorders is better avoided. To avoid confusion, we recommend PDSI as a newer, more accurate diagnostic term instead of LDK.


Prognostic models for predicting overall and cancer-specific survival of patients with initially diagnosed metastatic cervical squamous cell carcinoma: A study based on SEER database.
Cervical squamous cell carcinoma (CSCC) is the most common histological type of cervical cancer (CC). And mCSCC is the end stage of CSCC. The aim of this study was to develop prognostic nomograms that provide better predictions for overall survival (OS) and cancer-specific survival (CSS) in mCSCC patients. Data from patients with initially diagnosed mCSCC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The nomograms for OS and CSS were constructed based on Cox regression analysis. The validation of the newly established nomograms was evaluated by concordance index (C-index), calibration curves, and decision curve analyses (DCAs). A total of 2198 patients with mCSCC were included and randomly split into training (n = 1539) and validation (n = 659) cohorts in a 7:3 ratio. Multivariate analyses revealed that the prognostic variables significantly related to the OS and CSS were marital status, T stage, brain metastasis, lung metastasis, tumor size, number of positive lymph nodes, chemotherapy, and radiotherapy. The nomograms were constructed based on these factors. The C-index value of the nomograms for predicting OS and CSS was 0.714 and 0.683, respectively. The calibration curves of the nomograms showed good consistency between nomogram prediction and actual survival for both OS and CSS, and the DCAs showed great clinical usefulness of the nomograms. The mCSCC patients were classified into low- and high-risk groups based on the scores from the nomograms. In the validation cohort, mCSCC patients with low-risk had much higher OS and CSS than those with high-risk. We constructed nomograms for predicting the OS and CSS of patients with initially diagnosed mCSCC. Our models had satisfactory predictive performance and could be useful in survival prediction for mCSCC.


Spectrum of effectiveness of valproate in neuropsychiatry.
Valproate is principally effective in manic aspects of bipolar disorder. Tolerability has been somewhat more favorable for valproate than comparators, with the frequent adverse effects being gastrointestinal disturbances and weight gain. Total cholesterol and low-density lipoproteins are reduced by valproate. Valproate is effective and well tolerated when combined with lithium or antipsychotic drugs. Valproate is efficacious in mixed and euphoric mania. In studies of maintenance versus placebo and active comparators, patients initially treated with divalproex for mania had more robust long-term benefits than in the full sample analyses. In maintenance treatment, patients whose valproate serum levels were between 75 and 99 microg/ml had longer time to discontinuation for any reason or a new mood episode than did patients receiving placebo. The profile of utility in bipolar disorders is principally for core features of manic symptomatology (e.g., impulsivity, hyperactivity and irritability), with little evidence of benefit for anxiety or psychosis. Valproate appears useful in other disorders that have behavioral dimensions inclusive of the domains that valproate benefits in bipolar disorders, such as schizophrenia.


Survival of Bacterial and Parasitic Pathogens from Zebrafish (Danio rerio) After Cryopreservation and Thawing.
Cryopreservation is a common method used to preserve the sperm of various animal species, and it is widely used with zebrafish (Danio rerio). As with other animals, there is a possibility of paternal pathogen transmission through sperm. We evaluated the ability of five common and important pathogens of zebrafish to survive cryopreservation as used with zebrafish sperm and freezing without cryopreservant. We evaluated Mycobacterium chelonae, Mycobacterium marinum, and Edwardsiella ictaluri, each originally isolated from zebrafish, eggs of Pseuodocapillaria tomentosa, and spores of Pseudoloma neurophilia. Each mycobacterial isolate showed relatively minimal reduction in survival after freezing and thawing, particularly when subjected to cryopreservation. E. ictaluri also showed survival after cryopreservation, but exhibited a several log reduction after freezing at -80°C without cryopreservant. With P. neurophilia, two separate experiments conducted 3 years apart yielded very similar results, showing some, but reduced, survival of spores by using three different viability assays: SYTOX stain, Fungi-Fluor stain, and presence of a spore vacuole. Eggs of P. tomentosa showed no survival based on larvation of eggs when subjected to either freezing method. Given that four of the five pathogens exhibited survival after cryopreservation, we recommend that sperm samples or donor male zebrafish fish be tested for pathogens when sperm are to be stored by using cryopreservation.


Concentration-dependent effects of disulfonic stilbenes on colonic chloride transport.
Stripped rabbit colonic mucosa was studied in vitro in Ussing chambers to determine effects of the disulfonic stilbenes 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS) and 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) and the diuretic furosemide on unidirectional and net Cl fluxes. Results from these studies reveal that SITS (1 mM) added to either the serosal or mucosal bathing solution reduced both unidirectional Cl fluxes with no significant change in net Cl flux. The effects of SITS do not appear to be mediated by an effect on the shunt permeability since SITS (1 mM) did not alter either the intercept or slope of the Na concentration dependence of the serosal-to-mucosal Na flux. Furosemide (1 mM) decreased the serosal-to-mucosal Cl flux without altering short-circuit current (Isc) when added to the luminal bathing solution and reduced both unidirectional fluxes and increased Isc when added to the serosal bathing solution. DIDS (0.5 mM) added to the luminal bathing solution did not alter unidirectional Cl fluxes or Isc. However, serosal addition of DIDS produced dose-dependent changes in Cl transport. At 5 microM DIDS reduced the mucosal-to-serosal Cl flux without altering the serosal-to-mucosal flux or Isc. At 50 microM DIDS reduced the mucosal-to-serosal Cl flux and increased Isc, and at 0.5 mM DIDS increased the serosal-to-mucosal Cl flux, reduced the mucosal-to-serosal Cl flux, and increased Isc and transepithelial conductance. The effect of 0.5 mM DIDS on Isc was reduced by Ca removal from the serosal bathing solution and by the loop diuretics furosemide and bumetanide.(ABSTRACT TRUNCATED AT 250 WORDS)


Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis.
Visceral leishmaniasis (VL) is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania. Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL. Nanoliposomal artemisinin (NLA) was prepared by thin-film hydration method and optimized using Box-Behnken design with a mean particle diameter of 83±16 nm, polydispersity index of 0.2±0.03, zeta potential of -27.4±5.7 mV, and drug loading of 33.2%±2.1%. Morphological study of these nanoliposomes by microscopy showed a smooth and spherical surface. The mechanism of release of artemisinin from the liposomes followed the Higuchi model in vitro. NLA was free from concomitant signs of toxicity, both ex vivo in murine macrophages and in vivo in healthy BALB/c mice. NLA significantly denigrated the intracellular infection of Leishmania donovani amastigotes and the number of infected macrophages ex vivo with an IC50 of 6.0±1.4 µg/mL and 5.1±0.9 µg/mL, respectively. Following treatment in a murine model of VL, NLA demonstrated superior efficacy compared to artemisinin with a percentage inhibition of 82.4%±3.8% in the liver and 77.6%±5.5% in spleen at the highest dose of 20 mg/kg body weight with modulation of cell-mediated immunity towards protective Th1 type. This study is the first report on the use of a liposomal drug delivery system for artemisinin as a promising alternative intervention against VL.


Cytochemical localization of adenylate cyclase in cultured renal epithelial (A6) cells.
To characterize the vasopressin-adenylate cyclase (AC) signaling pathway in control of Na+ reabsorption in cultured renal (A6) cells, we determined the distribution of AC with a cytochemical technique using 5'-adenylylimidodiphosphate as substrate and cerium chloride as capturing agent. The addition of forskolin to the medium to stimulate AC activity increased the production of reaction deposits at the enzyme sites. To ensure that the cells were close to their physiological states, cytochemical reactions were performed on unfixed tissues. Subsequent postfixation adequately preserved the morphological features of the cells. AC was mainly restricted to the lateral folds of the cells while the apical membranes were devoid of any deposits. This result provided evidence that the V2-AC pathway is not present in the apical membrane and, hence, any vasopressin action on apical Na+ channels from the luminal side of the cell must involve other signaling pathways. The cytochemical results provided further morphological evidence of the functional coupling between the basolateral and apical membranes of renal cells. We examined the idea that highly variable basal rates of Na+ transport in young differentiating cell cultures may be related to the degree of AC activity. Cytochemical results apparently revealed highly variable amounts of deposits in these cells, but by quantitative analysis of AC activity we could find no significant differences between cells of 6, 14, and 21 days.


Induction of human mRNAs by interferon.
We have cloned a set of seven cDNAs corresponding to mRNAs induced by type I interferon in human cells, and are using these probes to characterize the response to interferon in detail. We have studied the kinetics of induction of each mRNA in three different human cell lines, the sensitivity of induction to cycloheximide, the effect of withdrawing interferon and the response of a receptor-positive interferon-resistant cell line.


Profile of bacterial isolates from suspected cases of infective endocarditis (IE): a retrospective study in a north Indian tertiary care hospital.
Infective Endocarditis (IE) is an emerging infection of the twenty-first century. This chronic Infection is mainly caused by bacteria, although fungi can also be associated with it. It is Important to know the profile of bacteria causing IE in a given region so as to suggest the empirical therapy for this serious illness. Blood culture isolates of clinically diagnosed or suspected cases of IE admitted to various wards of the All India Institute of Medical Sciences were analyzed retrospectively from January 2000 to June 2004. Standard techniques were used for the isolation and identification of the bacteria. Our study has demonstrated the predominance of Gram-negative bacilli, especially, Acinetobacter species and Pseudomonas aeruginosa, which are notorious for antimicrobial resistance, as the aetiological agents of IE. Amongst Gram-positive cocci, Enterococci exhibiting HLAR comprised the predominant species. Methicillin resistance among staphylococcal strains in this Tertiary care hospital is adding to the therapeutic challenge in the management of this serious illness. Although antimicrobial treatment should not be delayed in such cases, we cannot undermine the importance of isolation and identification of the etiological agents and the determination of the antimicrobial susceptibility for the management of these life-threatening conditions as well as for the formulation of guidelines for empirical therapy of these cases.


Interaction of a screw dislocation with a nano-sized, arbitrarily shaped inhomogeneity with interface stresses under anti-plane deformations.
We propose an elegant and concise general method for the solution of a problem involving the interaction of a screw dislocation and a nano-sized, arbitrarily shaped, elastic inhomogeneity in which the contribution of interface/surface elasticity is incorporated using a version of the Gurtin-Murdoch model. The analytic function inside the arbitrarily shaped inhomogeneity is represented in the form of a Faber series. The real periodic function arising from the contribution of the surface mechanics is then expanded as a Fourier series. The resulting system of linear algebraic equations is solved through the use of simple matrix algebra. When the elastic inhomogeneity represents a hole, our solution method simplifies considerably. Furthermore, we undertake an analytical investigation of the challenging problem of a screw dislocation interacting with two closely spaced nano-sized holes of arbitrary shape in the presence of surface stresses. Our solutions quite clearly demonstrate that the induced elastic fields and image force acting on the dislocation are indeed size-dependent.


Development of blood transfusion service in Sultanate of Oman.
Sultanate of Oman is geographically situated in south-west of Asia, having common borders on western side by the land with United Arab Emirates, Saudi Arabia and Yemen and with the Arabian Sea and the Gulf of Oman in the east and the north respectively. The country enjoys one of the best health care facilities including blood transfusion services in the region. Information was collected through informal personal interviews, digging out the past records, and the report presentations at various forums. A modest start by providing blood units through import, the country is now self-reliant on procuring blood units from voluntary non-remunerate blood donors within the sultanate. A steady growth of blood banks is witnessed in every aspect of blood banking including blood collection, blood processing and supply. Various modalities are adapted in promoting voluntary blood donation programme. Sultanate of Oman has created one of the best blood transfusion services in the region in providing safe blood for transfusion through voluntary donation, a use of blood components and irradiating blood products.


[Analgesia by transcutaneous electrical nerve stimulation (TENS)].
Although safe and effective pain control has been achieved using TENS in many fields of medicine, the application of this technique to dentistry remains almost unexplored. In this study the effectiveness of TENS in alleviating pre-existing orofacial pain, in providing analgesia during primary dental treatment of these patients and as an alternative to conventional local anaesthesia during cavity preparation in regular patients was examined. In approximately 80% of patients TENS successfully alleviated pre-existing orofacial pain. Primary dental treatment of these patients, however, was only possible under conventional local anaesthesia. Pain induced by cavity preparation was adequately suppressed by TENS in approximately 80% of all cases.


[Extra-osseous mandibular ameloblastoma].
Gingival ameloblastoma is a rare odontogenic tumor which shares the same histology as endo-osseous ameloblastoma but from which it differs in terms of its course by the absence of "local malignancy". There would appear to be two probable origins concerning this lesion: Serre debris and the epithelium of the gingival mucosa. However, the etiopathogenesis remains controversial, raising problems of pathological distinction from gingival basal cell carcinoma.


The effect of pH and lactose concentration on solvent production from whey permeate using Clostridium acetobutylicum.
A study was performed to optimize the production of solvents from whey permeate in batch fermentation using Clostridium acetobutylicum P262. Fermentations performed at relatively low pH values resulted in high solvent yields and productivities, but lactose utilization was incomplete. At higher pH values, lactose utilization was improved but acid production dominated over solvent production. When operating at the higher pH values, an increase in the initial lactose concentration of the whey permeate resulted in lower rates of lactose utilization, and this was accompanied by increased solvent production and decreased acid production. Analysis of data from several experiments revealed a strong inverse relationship between solvent yield and lactose utilization rate. Thus, conditions which minimize the lactose utilization rate, such as low culture pH values or high initial lactose concentrations, favor solventogenesis at the expense of acid production.


The use of thermal capsulorrhaphy in the treatment of multidirectional instability.
The purpose of this study is to report on our experience with thermal capsulorrhaphy in the treatment of multidirectional instability of the shoulder. Thirty-three consecutive patients (33 shoulders) with multidirectional instability were treated with arthroscopic thermal capsulorrhaphy. Twelve patients had a history of traumatic dislocation. Three patients had been previously treated with open inferior capsular shift procedures. At a mean follow-up of 36 months (range, 24-40 months), results were available for 30 patients. On the basis of the UCLA rating scale, out of a possible 35 points, the mean preoperative score was 16.7 points and postoperatively it was 30.1 points, with 3 excellent, 20 good, and 7 poor results. Twenty-three patients (76%) were returned to full activity. In our experience the majority of patients with multidirectional instability were able to return to their previous occupations in the armed forces following thermal capsulorrhaphy. More information further defining the biomechanical pathology of capsular laxity and the specific role of electrothermal shrinkage in treating shoulder instability is needed.


Recruiting at the edge: kinetic energy inhibits anchovy populations in the western Mediterranean.
The Strait of Gibraltar replenishes the Mediterranean with Atlantic waters through an intense eastward current known as the Atlantic Jet (AJ). The AJ fertilizes the southwestern Mediterranean and is considered to be the ultimate factor responsible for the comparatively high fish production of this region. Here, we perform an analysis of the available historical catches and catch per unit effort (CPUE), together with a long series of surface currents, kinetic energy and chlorophyll concentration. We show that the high kinetic energy of the AJ increases primary production but also negatively impacts the recruitment of anchovy. We contend that anchovy recruitment in the region is inhibited by the advection and dispersion of larvae and post-larvae during periods of strong advection by the AJ. The inhibitory impact of kinetic energy on anchovy landings is not a transient but rather a persistent state of the system. An exceptional combination of events creates an outbreak of this species in the Alboran Sea. These events depend on the Mediterranean-Atlantic exchange of water masses and, therefore, are highly sensitive to climate changes that are projected, though not always negatively, for fish landings.


Colonization of C57BL/6 Mice by a Potential Probiotic Bifidobacterium bifidum Strain under Germ-Free and Specific Pathogen-Free Conditions and during Experimental Colitis.
The effects of at least some probiotics are restricted to live, metabolically active bacteria at their site of action. Colonization of and persistence in the gastrointestinal tract is thus contributing to the beneficial effects of these strains. In the present study, colonization of an anti-inflammatory Bifidobacterium bifidum strain was studied in C57BL/6J mice under germ-free (GF) and specific pathogen-free (SPF) conditions as well as during dextran sulfate sodium (DSS)-induced colitis. B. bifidum S17/pMGC was unable to stably colonize C57BL/6J mice under SPF conditions. Mono-association of GF mice by three doses on consecutive days led to long-term, stable detection of up to 109 colony forming units (CFU) of B. bifidum S17/pMGC per g feces. This stable population was rapidly outcompeted upon transfer of mono-associated animals to SPF conditions. A B. animalis strain was isolated from the microbiota of these re-conventionalized mice. This B. animalis strain displayed significantly higher adhesion to murine CMT-93 intestinal epithelial cells (IECs) than to human Caco-2 IECs (p = 0.018). Conversely, B. bifidum S17/pMGC, i.e., a strain of human origin, adhered at significantly higher levels to human compared to murine IECs (p < 0.001). Disturbance of the gut ecology and induction of colitis by DSS-treatment did not promote colonization of the murine gastrointestinal tract (GIT) by B. bifidum S17/pMGC. Despite its poor colonization of the mouse GIT, B. bifidum S17/pMGC displayed a protective effect on DSS-induced colitis when administered as viable bacteria but not as UV-inactivated preparation. Collectively, these results suggest a selective disadvantage of B. bifidum S17/pMGC in the competition with the normal murine microbiota and an anti-inflammatory effect that requires live, metabolically active bacteria.


Prevalence of health-care providers asking older adults about their physical activity levels--United States, 1998.
Regular physical activity reduces the risk for heart disease, diabetes, and high blood pressure; helps in the control of weight; and maintains muscles, joints, and bone strength. Physical activity also might afford additional benefits for adults aged > or = 50 years by increasing coordination and balance, preventing falls, and maintaining independence. Despite these findings, the prevalence of inactivity increases with age, and approximately one third of older U.S. adults are not active during their leisure time. The national health objectives for 2010 include recommendations to increase the proportion of adults who engage in regular, preferably daily, moderate physical activity for > or = 30 minutes per day and vigorous physical activity > or = 3 days per week for > or = 20 minutes per occasion. To evaluate whether health-care providers ask about physical activity among older adults, CDC analyzed data from the 1998 National Health Interview Survey (NHIS). This report summarizes the results of that analysis, which indicate that approximately half of older adults who attended a routine check-up during the previous year reported being asked about physical activity by their health-care providers. To help older adults make lifestyle changes, health-care providers should ask older adults during routine check-ups about their physical activity levels.


The association between low skeletal muscle mass and delirium: results from the nationwide multi-centre Italian Delirium Day 2017.
Delirium and sarcopenia are common, although underdiagnosed, geriatric syndromes. Several pathological mechanisms can link delirium and low skeletal muscle mass, but few studies have investigated their association. We aimed to investigate (1) the association between delirium and low skeletal muscle mass and (2) the possible role of calf circumference mass in finding cases with delirium. The analyses were conducted employing the cross-sectional "Delirium Day" initiative, on patient 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes and hospices in Italy in 2017. Delirium was diagnosed as a 4 + score at the 4-AT scale. Low skeletal muscle mass was operationally defined as calf circumference ≤ 34 cm in males and ≤ 33 cm in females. Logistic regression models were used to investigate the association between low skeletal muscle mass and delirium. The discriminative ability of calf circumference was evaluated using non-parametric ROC analyses. A sample of 1675 patients was analyzed. In total, 73.6% of participants had low skeletal muscle mass and 24.1% exhibited delirium. Low skeletal muscle mass and delirium showed an independent association (OR: 1.50; 95% CI 1.09-2.08). In the subsample of patients without a diagnosis of dementia, the inclusion of calf circumference in a model based on age and sex significantly improved its discriminative accuracy [area under the curve (AUC) 0.69 vs 0.57, p < 0.001]. Low muscle mass is independently associated with delirium. In patients without a previous diagnosis of dementia, calf circumference may help to better identify those who develop delirium.


New Advances in RNAs.
Since the discovery of the first microRNA gene, lin-4, in Caenorhabditis elegans in 1993, many of this small regulatory genes have been reported in plants, viruses, and various kinds of animals. This announced a new world of RNA molecules, which subverted our traditional thinking about RNA. In this review, I summarized the main findings from researchers at different laboratories on microRNAs importance, functionality, production, and different aspects of their biologic activities.A narrative literature overview of relevant papers known to the author and that were retrieved from PubMed is presented.MicroRNA, a nonprotein-coding small RNA with almost 21 - 23 nucleotides in length, is an essential regulatory apparatus in the cells and their environment. They are crucial molecules for development, evolution, cellular differentiation, proliferation, embryogenesis, and cell death. Two classes of microRNAs exist: small temporal RNA--stRNA (miRNAs) and small interfering RNA--siRNAs (RNAi). The latter is a useful tool for the diagnosis, treatment, and prevention of diseases particularly cancer and viral diseases.There have been tremendous research regarding various aspects of these genes silencing and regulatory molecules which are preserved in all kinds of creatures. Currently, about 1% of the known human genes encode microRNAs.


A Randomised Controlled Trial of a Brief Online Mindfulness-Based Intervention on Paranoia in a Non-Clinical Sample.
Paranoia is common and distressing in the general population and can impact on health, emotional well-being and social functioning, such that effective interventions are needed. Brief online mindfulness-based interventions (MBIs) have been shown to reduce symptoms of anxiety and depression in non-clinical samples; however, at present, there is no research investigating whether they can reduce paranoia. The current study explored whether a brief online MBI increased levels of mindfulness and reduced levels of paranoia in a non-clinical population. The mediating effect of mindfulness on any changes in paranoia was also investigated. One hundred and ten participants were randomly allocated to either a 2-week online MBI including 10 min of daily guided mindfulness practice or to a waitlist control condition. Measures of mindfulness and paranoia were administered at baseline, post-intervention and 1-week follow-up. Participants in the MBI group displayed significantly greater reductions in paranoia compared to the waitlist control group. Mediation analysis demonstrated that change in mindfulness skills (specifically the observe, describe and non-react facets of the FFMQ) mediated the relationship between intervention type and change in levels of paranoia. This study provides evidence that a brief online MBI can significantly reduce levels of paranoia in a non-clinical population. Furthermore, increases in mindfulness skills from this brief online MBI can mediate reductions in non-clinical paranoia. The limitations of the study are discussed.


Producing Amorphous Solid Dispersions via Co-Precipitation and Spray Drying: Impact to Physicochemical and Biopharmaceutical Properties.
Many small-molecule active pharmaceutical ingredients (APIs) exhibit low aqueous solubility and benefit from generation of amorphous dispersions of the API and polymer to improve their dissolution properties. Spray drying and hot-melt extrusion are 2 common methods to produce these dispersions; however, for some systems, these approaches may not be optimal, and it would be beneficial to have an alternative route. Herein, amorphous solid dispersions of compound A, a low-solubility weak acid, and copovidone were made by conventional spray drying and co-precipitation. The physicochemical properties of the 2 materials were assessed via X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, and scanning electron microscopy. The amorphous dispersions were then formulated and tableted, and the performance was assessed in vivo and in vitro. In human dissolution studies, the co-precipitation tablets had slightly slower dissolution than the spray-dried dispersion, but both reached full release of compound A. In canine in vitro dissolution studies, the tablets showed comparable dissolution profiles. Finally, canine pharmacokinetic studies showed that the materials had comparable values for the area under the curve, bioavailability, and Cmax. Based on the summarized data, we conclude that for some APIs, co-precipitation is a viable alternative to spray drying to make solid amorphous dispersions while maintaining desirable physicochemical and biopharmaceutical characteristics.


Nocebo effect in randomized clinical trials of antidepressants in children and adolescents: systematic review and meta-analysis.
To compare the incidence of adverse events between active and placebo arms of randomized clinical trials in depressive children and adolescents (C&A) with antidepressant treatments, in order to look for similarities in both groups that allow to establish a possible nocebo effect. Systematic search strategy (January 1974-March 2013) in electronic databases, conference abstracts, and reference list of systematic reviews and included studies to identify parallel randomized placebo-controlled trials of antidepressants in C&A (<19 years) with major depressive disorder, and one or more interventions of any orally administered antidepressant. The pooled adverse events were calculated based on a fixed-effect model and statistical analysis involved the risk ratio (RR) of adverse events, with 95% confidence intervals (95% CI). Sixteen studies were included in the review, of which seven studies with a sample of 1911 patients had data to include in the meta-analysis. There was similar risk for the incidence of adverse events between non-active and active group (global RR 1.04, 95% CI: 0.97-1.11). Depressive C&A allocated to placebo or active group had similar risk to develop adverse events. These similarities in both groups are attributed to the nocebo effect. It is of note that defining "nocebo" effects is challenging in clinical populations because adverse effects may be attributed to the intervention or may be manifestation of the disease itself. The inclusion of a no-treatment arm may be warranted. Nocebo effects are likely when adverse events of placebo mimic the adverse events of active treatment, as was the case here.


[Fluorescence spectroscopic analysis of huminite of the peat and soft brown coal].
The huminite of the peat and soft brown coal in the Zhenan basin, western Yunnan, has been studied by means of fluorescence microscopy. The study reveals that the fluorescent features of the huminite are considerabably complicated: some huminite, like liptinites, can give out dark yellow to yellow fluorescent light, I546 ranging from 8.13 to 13.17; and the fluorescent spectrum having one peak or two peaks, lambdamax ranging from 555 to 585nm and Q650/500 from 0.60 to 2.93. Most of huminites do not give out fluorescent light or give out dark brown fluorescent light, I546 ranging from 0 to 5.38. Because of having extraordinarily weak fluorescent light, it is very difficult to obtain their fluorescent spectrum. Nevertherless, after being stimulated for several minutes, some huminites that do not give out fluorescent light or give out dark brown fluorescent light may give out yellowish brown to dark orange fluorescent light, I546 ranging from 6.12 to 12.17, lambdamax. from 590 to 615nm and Q650/600 from 3.49 to 4.31. With the stimulating time becoming longer (10 to 20min), some huminites,may give out sharper yellow fluorescent light, I546 ranging from 12.18 to 20.01, lambdamax from 555 to 595nm and Q650/500 from 0.87 to 1.60.


[Specificity of spatial organization of evoked EEG rhythms in patients with paranoid schizophrenia].
The study aimed at analyzing the spatial patterns of evoked event-related oscillations in patients with paranoid schizophrenia and their relationship with clinical symptoms of disease. Evoked delta, theta, alpha, beta, and gamma rhythms in response to target auditory stimulus in an oddball paradigm were studied in 21 schizophrenic patients and 22 healthy subjects. The independent spatial patterns were revealed within each of the frequency range using the principal component analysis. Each spatial pattern was characterized by the specificity of intra- and inter-hemispheric relations. The schizophrenic patients were characterized by a decrease in the evoked activity in the theta range with the most pronounced changes in the frontal-central areas of the right hemisphere and parietal-occipital areas bilaterally. Associations of the evoked rhythms with PANSS positive and negative symptoms were identified. The study demonstrated the high functional significance of evoked EEG rhythms changes for neurophysiological characteristics of patients with paranoid schizophrenia.


Changes in arterial stiffness after eccentric versus concentric cycling.
This study compared changes in brachial-ankle pulse wave velocity (baPWV) after concentric (CON) versus eccentric (ECC) cycling. It was hypothesized that baPWV would increase after the first ECC bout (ECC1) because of muscle damage, but not after the second ECC bout (ECC2), and would decrease after CON. Fifteen young (aged 20-30 years) men performed 2 bouts of 30-min ECC (ECC1 and ECC2) at 60% of maximal CON power output and 2 bouts of 30-min CON at the same intensity as that of ECC (CON1), and at the same oxygen consumption as that of ECC (CON2) every 2 weeks. Oxygen uptake during the cycling was recorded, and baPWV was measured before and at 0.5, 1, 24, and 48 h after each cycling bout. Maximal voluntary contraction (MVC) torque and muscle soreness of the knee extensors were assessed before and at 24 and 48 h after each cycling bout. Changes in these variables over time were compared among the 4 cycling bouts by 2-way repeated-measured ANOVA. baPWV decreased (P < 0.05) 8% from the baseline (1119 ± 116 cm/s) at 0.5 h after CON1 (1028 ± 126 cm/s), but no significant changes were evident after ECC1, ECC2, and CON2. MVC torque decreased 10% from the baseline at 24 h after ECC1, but no significant changes were evident after CON1, CON2, and ECC2. These results did not support the hypothesis, and suggest that minor muscle damage induced by eccentric cycling does not affect arterial stiffness.


Curative interstitial brachytherapy for early stage carcinoma lip.
Brachytherapy is potentially useful in the treatment of head-and-neck cancers, because most tumor sites, such as the lip, tongue, floor of mouth, tonsil, pharynx, nasopharynx, sinuses, and neck, are accessible for the placement of afterloading applicators and catheters. It has the advantage of delivering a higher radiation dose to the tumor while sparing surrounding normal tissue from radiation. Furthermore, the overall treatment duration is shorter, and the dose distribution confirms to tumor shape. Brachytherapy is used as "monotherapy" for the treatment of small primary tumors or recurrent disease after external beam radiation therapy (EBRT). Small cancers of the lip (less than 2 cm) are treated equally well with surgery or radiation therapy with excellent cosmetic and functional results seen in radiation therapy. We treated an 18-year old male diagnosed as stage I carcinoma lip with curative interstitial brachytherapy. He was treated to a dose of 3 Gy per fraction, two fractions per day at interval of 6 hours between the two fractions for 6 days. He therefore received a total dose of 36 Gy with High Dose Rate (HDR) Brachytherapy, which is equivalent to 58.36 Gy conventional radiotherapy dose. At two months follow, the patient is clinically disease free and has no complaints.


Alterations of gastrin secretion in obese rats with ventromedial hypothalamic lesions.
Basal plasma gastrin levels were significantly higher in obese rats induced by ventromedial hypothalamic lesions (VMH rats) than in sham-operated controls. Gastrin secretion in response to insulin hypoglycemia and a liquid diet load was higher in VMH rats than in controls. The antral gastrin concentration was also elevated in VMH rats. Pair-fed rats with VMH lesions showed increased gastrin secretion as did the non-pair-fed group. These results show that gastrointestinal hormone secretions as well as pancreatic endocrine function are abnormal in obese rats with VMH lesions. Increased gastrin secretion is probably induced by factors other then hyperphagia, such as disturbance of the autonomic nervous system due to the VMH lesions.


The effect of Nd:YAG laser capsulotomy size on refraction and visual acuity.
To determine the effect of Nd:YAG laser posterior capsulotomy size on refraction and visual acuity. A total of 128 pseudophakic eyes (108 patients) were included in this study and divided into two groups by capsulotomy size: 80 eyes had small capsulotomies (<4 mm) without dilating the pupil and 48 eyes had large capsulotomies (> or = 4 mm and <7 mm) after dilating the pupil. Visual acuities and refractive errors were measured preoperatively and 1, 14, 30, and 90 days postoperatively. Results were analyzed statistically. The change in spherical equivalent refraction was 0.38 +/- 0.52 diopters (D) in the small capsulotomy group and 0.22 +/- 0.36 D in the large capsulotomy group. No statistically significant differences were noted in spherical equivalent refraction change (P=.47) or capsulotomy size (P=.0387) between the two groups. The size of posterior capsulotomy does not significantly affect refraction and visual acuity.


Screening of potentially crucial genes and regulatory factors involved in epithelial ovarian cancer using microarray analysis.
The present study aimed to screen potential genes implicated in epithelial ovarian cancer (EOC) and to further understand the molecular pathogenesis of EOC. In order to do this, datasets GSE14407 (containing 12 human ovarian cancer epithelia samples and 12 normal epithelia samples) and GSE29220 (containing 11 salivary transcriptomes from ovarian cancer patients with serous papillary adenocarcinoma and 11 matched controls) were obtained from the Gene Expression Omnibus. Differentially expressed genes (DEGs) within these datasets were screened using the Linear Models for Microarray Data package, and potential gene functions were predicted by functional and pathway enrichment analyses. Additionally, module analysis of protein-protein interaction networks was performed using MCODE software in Cytoscape. The potential microRNAs (miRNAs/miRs) and transcription factors (TFs) regulating DEGs were also analyzed, and the integrated TF-DEG and miRNA-DEG regulatory networks were visualized with Cytoscape. In total, 31 upregulated DEGs and 64 downregulated DEGs were screened. The upregulated DEGs, such as centromere protein F (CENPF) and ubiquitin like with PHD and ring finger domains 1 (UHRF1), were significantly associated with the cell cycle and were regulated by the TF nuclear transcription factor Y (NF-Y). CENPF was modulated by miR-373, and UHRF1 was regulated by miR-146a. The downregulated DEGs, such as aldehyde dehydrogenase 1 family member A2 (ALDH1A2), were distinctly involved in the response to estrogen stimulus and modulated by tumor protein 53 (TP53); protocadherin 9 (PCDH9) was regulated by TP53, miR-92b-3p and miR-137. The DEGs, including CENPF, UHRF1, ALDH1A2 and PCDH9, and a set of gene regulators, including all NFY genes, TP53, miR-373, miR-146a, miR-92b-3p and miR-137, may be involved in the pathogenesis of EOC.


[Mazindol effects on the salivary and gastric acid secretory mechanisms].
The effects of mazindol on the salivary secretion of dogs was investigated. Mazindol (2 mg/kg, i.v.) decreased the volume and pressure of salivary secretion induced by either chemical (carpronium) stimulation or electrical nerve stimulation. It also reduced spontaneous salivary secretion. Secretion velocity in the mazindol treated group was significantly less than in the physiological saline administered control group at 4 to 6 min after injection. Saline and mazindol produced no significance differences in Na+, Cl- or K+ concentrations in the saliva or serum. Thus mazindol inhibition of salivary secretion was not caused by ion transport. The existence of some other inhibitory mechanism is suggested. The effects of mazindol on the peripheral and central control of gastric acid secretion was also investigated in rats. Gastric acid secretion induced by direct application of cholinergic agents on oxyntic cells was not affected by mazindol. Gastric acid secretion induced by insulin and/or 2-DG, on the other hand, was markedly inhibited by intra-hypothalamic injection or systemic (i.v.) injections of mazindol. Electro-osmotic mazindol mimicked the effects of glucose in the lateral (inhibition) and ventromedial (excitation) hypothalamus. The results suggest that the inhibitory effects of mazindol on salivary secretion may be through the hypothalamic feeding control centers. Mazindol also directly affected gastric acid secretory neurons in the lateral hypothalamus. It might thus be expected to be effective in the treatment of obesity.


[Camparative analysis of two studies concerning the teacher-student relationship after a 10 year interval].
The nursing profession is a profession dealing with the person and cannot be detached from the relationship that is established between two people who differ in the individual features but share the basic themes of Birth-Life-Health-Illness-Death. Since this relationship plays a fundamental role in the growth process of students and, later, in their professional life, the training process must take into account the need to train students to relate with others: in the lack of this, students will not be able to transmit their competence to patients. The aim of this study is to assess the relational component in the teacher/student relationship in the field of nursing, comparing the results obtained from a similar study performed in 1996 to evaluate whether the relational needs of nursing students have changed since then.


Quantum effects on criticality of an Ising model in scale-free networks: Beyond mean-field universality class.
We study the effect of quantum fluctuations on the critical behavior of the Ising ferromagnetic phase transitions that do not belong to the mean-field universality class. A model system is considered, in which Ising spins are placed on the nodes of a scale-free network. Our Monte Carlo analysis shows that the critical exponents differ from those of mean-field phase transitions when degree exponent gamma is in the range 3<gamma<5 . This confirms earlier analytic calculations based on ansatzes and approximation methods. As we apply quantum fluctuations by means of a magnetic field perpendicular to the Ising spin direction, the transition temperature T(c) decreases with increasing magnetic field strength. We find, however, that the quantum fluctuations do not alter the critical exponents and the universality class remains unchanged.


The optimal age of measles immunisation in low-income countries: a secondary analysis of the assumptions underlying the current policy.
The current policy of measles vaccination at 9 months of age was decided in the mid-1970s. The policy was not tested for impact on child survival but was based on studies of seroconversion after measles vaccination at different ages. The authors examined the empirical evidence for the six underlying assumptions. Secondary analysis. These assumptions have not been research issues. Hence, the authors examined case reports to assess the empirical evidence for the original assumptions. The authors used existing reviews, and in December 2011, the authors made a PubMed search for relevant papers. The title and abstract of papers in English, French, Portuguese, Spanish, German and Scandinavian languages were assessed to ascertain whether the paper was potentially relevant. Based on cumulative measles incidence figures, the authors calculated how many measles cases had been prevented assuming everybody was vaccinated at a specific age, how many 'vaccine failures' would occur after the age of vaccination and how many cases would occur before the specific age of vaccination. In the combined analyses of several studies, the authors used the Mantel-Haenszel weighted RR stratifying for study or age groups to estimate common trends. African community studies of measles infection. Consistency between assumptions and empirical evidence and the predicted effect on mortality. In retrospect, the major assumptions were based on false premises. First, in the single study examining this point, seronegative vaccinated children had considerable protection against measles infection. Second, in 18 community studies, vaccinated measles cases ('vaccine failures') had threefold lower case death than unvaccinated cases. Third, in 24 community studies, infants had twofold higher case death than older measles cases. Fourth, the only study examining the assumption that 'vaccine failures' lead to lack of confidence found the opposite because vaccinated children had milder measles infection. Fifth, a one-dose policy was recommended. However, the two randomised trials of early two-dose measles vaccination compared with one-dose vaccination found significantly reduced mortality until 3 years of age. Thus, current evidence suggests that the optimal age for a single dose of measles vaccine should have been 6 or 7 months resulting in fewer severe unvaccinated cases among infants but more mild 'vaccine failures' among older children. Furthermore, the two-dose trials indicate that measles vaccine reduces mortality from other causes than measles infection. Many lives may have been lost by not determining the optimal age of measles vaccination. Since seroconversion continues to be the basis for policy, the current recommendation is to increase the age of measles vaccination to 12 months in countries with limited measles transmission. This policy may lead to an increase in child mortality.


Cleavage specificity of the subtilisin-like protease C1 from soybean.
The cleavage specificity of protease C1, isolated from soybean (Glycine max (L.) Merrill) seedling cotyledons, was examined using oligopeptide substrates in an HPLC based assay. A series of peptides based on the sequence Ac-KVEKEESEEGE-NH2 was used, mimicking a natural cleavage site of protease C1 in the alpha subunit of the storage protein beta-conglycinin. A study of substrate peptides truncated from either the N- or C-terminus indicates that the minimal requirements for cleavage by protease C2 are three residues N-terminal to the cleaved bond, and two residues C-terminal (i.e. P3-P2'). The maximal rate of cleavage is reached with substrates containing four to five residues N-terminal to the cleaved bond and four residues C-terminal (i.e. P4 or P5 to P4'). The importance of Glu residues at the P1, P1', and P4 positions was examined using a series of substituted nonapeptides (P5-P4') with a base sequence of Ac-KVEKEESEE-NH2. At the P1 position, the relative ranking, based on kcat/Km, was E>Q>K>A>D>F>S. Substitutions at the P1' position yield the ranking E congruent withQ>A>S>D>K>F, while those at P4' had less effect on kcat/Km, yielding the ranking F congruent with S congruent with E congruent withD>K>A congruent withQ. These data show that protease C1 prefers to cleave at Glu-Glu and Glu-Gln bonds, and that the nature of the P4' position is less important. The fact that there is specificity in the cleavage of the oligopeptides suggests that the more limited specific cleavage of the alpha and alpha' subunits of beta-conglycinin by protease C1 is due to a combination of the sequence cleavage specificity of the protease and the accessibility of appropriate scissile peptide bonds on the surface of the substrate protein.


Complete Genome Sequence of Citrobacter freundii Myophage Michonne.
Citrobacter freundii is a Gram-negative opportunistic pathogen that causes dangerous infections such as neonatal meningitis. C. freundii also harbors antibiotic resistance, making phages infecting this host valuable tools. Here, we announce the complete genome of the C. freundii FelixO1-like myophage Michonne and describe its notable features.


Inverse association between serum adiponectin level and transaminase activities in Japanese male workers.
Since a novel polypeptide named adiponectin was shown to prevent the development of steatosis and steatohepatitis in animal models, we studied whether it was also possible in a clinical situation. Associations between serum adiponectin levels and serum transaminase activities were studied in 791 Japanese males who were not heavy drinkers, and had no autoimmune or HBV- or HCV-induced liver diseases. Various markers of metabolic diseases including levels of body mass index (BMI), serum triglyceride, total cholesterol, and insulin resistance assessed by the homeostasis model were significantly higher in subjects with increased transaminase activities when compared to those with normal activities. Single regression analyses demonstrated that the logarithmic serum adiponectin level was inversely correlated with the levels of logarithmic serum AST (r=-0.229, P<0.0001), ALT (r=-0.305, P<0.0001), and gammaGTP (r=-0.278, P<0.0001). Even in multiple regression analyses in which subjects' age and levels of BMI, serum triglyceride, total cholesterol, and insulin resistance were adjusted, the inverse correlations were significant (P=0.0426, 0.0332, and 0.0011, respectively). Hypoadiponectinemia may worsen liver diseases associated with metabolic diseases in clinical cases. In addition to aggravation of insulin resistance and hyperlipidemia, some hypoadiponectinemia specific mechanisms may stand behind the association.


Cardiovascular effects of air pollution.
Air pollution is composed of particulate matter (PM) and gaseous pollutants, such as nitrogen dioxide and ozone. PM is classified according to size into coarse particles (PM10), fine particles (PM2.5) and ultrafine particles. We aim to provide an original review of the scientific evidence from epidemiological and experimental studies examining the cardiovascular effects of outdoor air pollution. Pooled epidemiological studies reported that a 10μg/m3 increase in long-term exposure to PM2.5 was associated with an 11% increase in cardiovascular mortality. Increased cardiovascular mortality was also related to long-term and short-term exposure to nitrogen dioxide. Exposure to air pollution and road traffic was associated with an increased risk of arteriosclerosis, as shown by premature aortic and coronary calcification. Short-term increases in air pollution were associated with an increased risk of myocardial infarction, stroke and acute heart failure. The risk was increased even when pollutant concentrations were below European standards. Reinforcing the evidence from epidemiological studies, numerous experimental studies demonstrated that air pollution promotes a systemic vascular oxidative stress reaction. Radical oxygen species induce endothelial dysfunction, monocyte activation and some proatherogenic changes in lipoproteins, which initiate plaque formation. Furthermore, air pollution favours thrombus formation, because of an increase in coagulation factors and platelet activation. Experimental studies also indicate that some pollutants have more harmful cardiovascular effects, such as combustion-derived PM2.5 and ultrafine particles. Air pollution is a major contributor to cardiovascular diseases. Promotion of safer air quality appears to be a new challenge in cardiovascular disease prevention.


Coulombic and hydrophobic interactions in the first intracellular loop are vital for bradykinin B2 receptor ligand binding and consequent signal transduction.
The role of the first intracellular loop (IC1) in the function of the rat bradykinin B2 receptor (BKB2R) was probed. On the basis of the bovine rhodopsin X-ray structure, the BKB2R IC1 consists of six residues: (60)HKTNCT. Exchange of this sequence with the bradykinin B1 receptor IC1 (PRRQLN) resulted in a chimera which bound bradykinin and signaled as wild-type (WT) BKB2R. In contrast, a chimera containing the IC1 of rat angiotensin II type Ia receptor (AT1aR) (YMKLKT) did not bind BK nor signal in response to BK at a concentration as high as 5 microM. ELISA illustrated that this receptor was still processed and inserted into the plasma membrane. Employing portions of the IC1, we observed that (60)HKT of BKB2R could be exchanged as a group with either the BKB1R (PRR) or AT1aR (YMK) with no change in receptor binding or signaling activities. When only the YM of AT1aR replaced the HK of BKB2R, leaving the N-terminal portion of IC1 without a positively charged residue, binding and signaling were reduced by more than 70%. When only N63 was replaced with the corresponding leucine of AT1aR, binding and signaling were ablated. In fact, replacement of the entire IC1 with the AT1aR except for N63 resulted in binding and signaling as WT BKB2R. However, N63 could be replaced by glutamine (in BKB1R) or aspartate and continued to function as WT BKB2R. NMR data indicated that the BKB2R IC1 extends beyond the bovine rhodopsin prototype to include HKTNCTVAEI. When E68 was exchanged with a serine (in AT1aR), ligand binding decreased by 60% and PI turnover decreased by 69%. Molecular modeling points to a strict requirement for a hydrophilic residue at position 63 (N) at the middle of the IC1 and a Coulombic charge interaction between the positive charges (H60 and K61) at the N-terminus and a negative charge (E68) at the C-terminus of the IC1.


Efficient integration of recombinant adeno-associated virus DNA vectors requires a p5-rep sequence in cis.
The initial aim of this study was to combine attributes of adeno-associated virus (AAV) and adenovirus (Ad) gene therapy vectors to generate an Ad-AAV hybrid vector allowing efficient site-specific integration with Ad vectors. In executing our experimental strategy, we found that, in addition to the known incompatibility of Rep expression and Ad growth, an equally large obstacle was presented by the inefficiency of the integration event when using traditional recombinant AAV (rAAV) vectors. This study has addressed both of these problems. We have shown that a first-generation Ad can be generated that expresses Rep proteins at levels consistent with those found in wild-type AAV (wtAAV) infections and that Rep-mediated AAV persistence can occur in the presence of first-generation Ad vectors. Our finding that traditional rAAV plasmid vectors lack integration potency compared to wtAAV plasmid constructs (10- to 100-fold differences) was unexpected but led to the discovery of a previously unidentified AAV integration enhancer sequence element which functions in cis to an AAV inverted terminal repeat-flanked target gene. rAAV constructs containing left-end AAV sequence, including the p5-rep promoter sequence, integrate efficiently in a site-specific manner. The identification of this novel AAV integration enhancer element is consistent with previous studies, which have indicated that a high frequency of wtAAV recombinant junction formation occurs in the vicinity of the p5 promoter, and recent studies have demonstrated a role for this region in AAV DNA replication. Understanding the contribution of this element to the mechanism of AAV integration will be critical to the use of AAV vectors for targeted gene transfer applications.