Molecular cloning of squid N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase and synthesis of a unique chondroitin sulfate containing E-D hybrid tetrasaccharide structure by the recombinant enzyme.
N-Acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) transfers sulfate to position 6 of GalNAc(4SO(4)) residues in chondroitin sulfate (CS). We previously purified squid GalNAc4S-6ST and cloned a cDNA encoding the partial sequence of squid GalNAc4S-6ST. In this paper, we cloned squid GalNAc4S-6ST cDNA containing a full open reading frame and characterized the recombinant squid GalNAc4S-6ST. The cDNA predicts a Type II transmembrane protein composed of 425 amino acid residues. The recombinant squid GalNAc4S-6ST transferred sulfate preferentially to the internal GalNAc(4SO(4)) residues of chondroitin sulfate A (CS-A); nevertheless, the nonreducing terminal GalNAc(4SO(4)) could be sulfated efficiently when the GalNAc(4SO(4)) residue was included in the unique nonreducing terminal structure, GalNAc(4SO(4))-GlcA(2SO(4))-GalNAc(6SO(4)), which was previously found in CS-A. Shark cartilage chondroitin sulfate C (CS-C) and chondroitin sulfate D (CS-D), poor acceptors for human GalNAc4S-6ST, served as the good acceptors for the recombinant squid GalNAc4S-6ST. Analysis of the sulfated products formed from CS-C and CS-D revealed that GalNAc(4SO(4)) residues included in a tetrasaccharide sequence, GlcA-GalNAc(4SO(4))-GlcA(2SO(4))-GalNAc(6SO(4)), were sulfated efficiently by squid GalNAc4S-6ST, and the E-D hybrid tetrasaccharide sequence, GlcA-GalNAc(4,6-SO(4))-GlcA(2SO(4))-GalNAc(6SO(4)) was generated in the resulting sulfated glycosaminoglycans. These observations indicate that the recombinant squid GalNAc4S-6ST is a useful enzyme for preparing a unique chondroitin sulfate containing the E-D hybrid tetrasaccharide structure.


The application of CD73 in minimal residual disease monitoring using flow cytometry in B-cell acute lymphoblastic leukemia.
The expression of CD73 by flow cytometry (FC) in bone marrow (BM) specimens of B-cell acute lymphoblastic leukemia (B-ALL) with or without minimal residual disease (MRD) was studied, and its advantages were evaluated using the MRD assay. This study also detected the expression profile of CD73 in hematogones and mature B cells in BM specimens of 18 healthy donors. Results showed that the mean value of CD73 expression in MRD-positive B cells was 6-fold greater than that in the MRD negative ones. Also, 41.82% MRD-positive B-ALL cases expressed high CD73 and the sensitivity of CD73-based MRD detection reached 10(-4). Since the expression of CD73 increases with the maturation of normal B cells, it is better to mix it with CD34, CD10 and CD20 in one tube to prevent the disturbance of mature B cells. CD73 is recommended as an optional MRD marker for B-ALL patients by using FC.


[Infectious endocarditis of the left heart atrium in injection drug addicts].
To study etiology, clinical picture, course and prognosis of left heart infection endocarditis (LHIE) in drug addicts. 61 drug addicts entered the study. 14 of them had lesions of the left heart valves (group 1), 11--of the right and left heart valves (group 2), 36--of the tricuspid valve (group 3), 39 control patients with LHIE had no addiction. Mean age in group 1 was 25.9 +/- 8.8 years, in group 4--48.3 +/- 12.6 years, p < 0.001. Females prevailed in group 3, males--in group 4. Splenomegaly was more frequent in the addicts. Lung lesions (abscesses and infarction) prevailed in groups 2 and 3. Cardiac failure was found more frequently in groups 1 and 4, edema--in group 3, brain affections--in groups 1 and 4. Renal damage was encountered with equal frequency in the addicts and non-addicts. The addicts had, largely, infarctions, non-addicts--glomerulonephritis. Viral hepatitis C was associated with drug addiction. Blood seedings were on the whole positive in 54%, in drug addicts--in 69%. St. aureus predominated (44%). In group 3 it was detected in 72%. It was higher than in groups 4 and 1 (p < 0.001, p < 0.01, respectively). Lethality in group 1 (57%) was higher than in group 3 (22%, p < 0.05) and group 2 (18%, p < 0.01). The leading cause of death in group 1 was cerebral thromboembolism with development of meningoencephalitis. Other causes--progressive cardiac and renal failure.


Intrapulmonary antigen deposition in the human lung: local responses.
We hypothesized that, as in animal models, localized deposition of antigen into the human lung would induce local inflammatory and immune responses in antigen-exposed sites. To test this hypothesis, segmental instillation of a well-characterized, highly immunogenic, soluble antigen, keyhole limpet hemocyanin (KLH) was performed in 10 healthy, nonsmoking volunteers. Ten to fifteen days after instillation, bronchoalveolar lavage (BAL) was performed in immunized segments (IS) and contralateral control segments (CS) and local responses to antigen instillation were assessed by comparing IS and CS BAL. Greater albumin concentrations and cell recoveries were found in IS than in CS BAL, suggesting local inflammation. Although total numbers of each cell type were increased, relative proportions of alveolar macrophages, lymphocytes, and neutrophils were similar in IS and CS BAL. CD4/CD8 ratios in IS BAL samples were greater than those in CS samples, because of higher numbers of CD4+ lymphocytes in IS than in CS BAL but similar numbers of CD8+ lymphocytes. Anti-KLH IgG and IgA concentrations were greater in IS than in CS BAL. However, anti-KLH IgG/albumin ratios were similar in IS BAL and serum, suggesting that anti-KLH IgG had reached IS by passive transudation from the circulation. In contrast, anti-KLH IgA/albumin concentrations were greater in IS BAL than in serum, suggesting local production, and/or active transport of serum-derived anti-KLH IgA into the IS. Fractionation of serum and IS BAL on sucrose gradients demonstrated that anti-KLH IgA activity was largely associated with 11S polymeric IgA in both locations.(ABSTRACT TRUNCATED AT 250 WORDS)


A faster and easier biodosimetry method based on calyculin A-induced premature chromosome condensation (PCC) by scoring excess objects.
Dicentric analysis and the ring PCC assay as established biodosimetry methods both have limitations in the estimation of absorbed doses in suspected overexposure cases between 5 and 10 Gy. The proposed method based on calyculin A-induced PCC overcomes these limitations by scoring excess objects as the endpoint. This new scoring method can potentially serve as a faster and up-scalable approach that complements the existing methods with higher accuracy at different dose ranges. It can also potentially be performed by less skilled workers when no automated system is available in mass casualty emergency cases to assist with the triage of patients. Additionally, it offers the possibility to further reduce the sample size and PCC induction time. In this pilot study, a calibration curve for excess objects was constructed using the new scoring method for the first time and a blind validation test composed of three unknown doses was carried out. Almost all the dose estimates were within the 95% confidence limits of the actual test doses by scoring only 50-100 PCC spreads. This method was found to be more accurate than ring PCC for doses below 10 Gy.


Some peculiarities of the pulmonary phagocytotic response: dust retention kinetics and silicosis development during long term exposure of rats to high quartz dust levels.
Rats were exposed to quartz dust (about 90 mg/m3) for five hours a day, five times a week either throughout the 48 weeks of the experiment or for a total of 40 weeks plus eight weeks of "rest." Cytological study of bronchoalveolar lavage showed that at a certain level of silicotic changes in the lungs, a pronounced breakdown in pulmonary dust clearance by macrophages could be observed. There was, however, a concomitant compensatory increase in the contribution to pulmonary phagocytosis by the neutrophil leukocytes (NL). As a result, pulmonary dust kinetics could be mathematically described using a constant clearance rate both throughout the 48 weeks of exposure and during the eight weeks after the end of the 40 week exposure. It is shown in a separate experiment that enhanced recruitment of NL into the airways may be due not only to an attractant effect of the products of macrophage breakdown (PMB) themselves but also to the release of an NL attractant factor by viable macrophages activated under influence of the PMB.


Late-onset of spinal neurodegeneration in knock-in mice expressing a mutant BiP.
Most human neurodegenerative diseases are sporadic, and appear later in life. While the underlying mechanisms of the progression of those diseases are still unclear, investigations into the familial forms of comparable diseases suggest that endoplasmic reticulum (ER) stress is involved in the pathogenesis. Binding immunoglobulin protein (BiP) is an ER chaperone that is central to ER function. We produced knock-in mice expressing a mutant BiP that lacked the retrieval sequence in order to evaluate the effect of a functional defect in an ER chaperone in multi-cellular organisms. Here we report that heterozygous mutant BiP mice revealed motor disabilities in aging. We found a degeneration of some motoneurons in the spinal cord accompanied by accumulations of ubiquitinated proteins. The defect in retrieval of BiP by the KDEL receptor leads to impaired activities in quality control and autophagy, suggesting that functional defects in the ER chaperones may contribute to the late onset of neurodegenerative diseases.


Oxygen microelectrode response to oxygen pressures up to 15 ATA.
Polarographic measurements of oxygen at high pressures were made at 21-22 degrees C with open-type Wood's metal microelectrodes with tip diameter about 5 mu. Although the sensitivity of the individual electrodes ranged from 3.1 x 10(-10) to 8.8 x 10(-12) amps/mm Hg of O2, the oxygen current was always a straight line function of Po2 from 21% O2 at ambient pressure (Po2 = 160 mm Hg) to 100% O2 at 200 psig (Po2 = 11,102 mm Hg). Compression to 200 psig with 100% nitrogen produced no significant change in microelectrode current, showing that the microelectrodes are insensitive to pressure alone.


Domestic wastewater treatment as a net energy producer--can this be achieved?
In seeking greater sustainability in water resources management, wastewater is now being considered more as a resource than as a waste-a resource for water, for plant nutrients, and for energy. Energy, the primary focus of this article, can be obtained from wastewater's organic as well as from its thermal content. Also, using wastewater's nitrogen and P nutrients for plant fertilization, rather than wasting them, helps offset the high energy cost of producing synthetic fertilizers. Microbial fuel cells offer potential for direct biological conversion of wastewater's organic materials into electricity, although significant improvements are needed for this process to be competitive with anaerobic biological conversion of wastewater organics into biogas, a renewable fuel used in electricity generation. Newer membrane processes coupled with complete anaerobic treatment of wastewater offer the potential for wastewater treatment to become a net generator of energy, rather than the large energy consumer that it is today.


Physician payment policies: impacts and implications.
This paper reviews recent changes in physician payment policies, examines evidence on their impacts, and discusses their implications for researchers and policy makers. It first develops a conceptual framework to help explore the economic incentives inherent in different physician payment schemes. It then reviews evidence on the impacts of recent changes in physician payment methods; first, for free-for-service, and then for capitated systems like HMOs. It concludes that much more research needs to be conducted on HMOs to determine the impact of different physician payment incentives on utilization, expenditures, clinical outcomes, and patient satisfaction.


Surveillance strategy for small asymptomatic non-functional pancreatic neuroendocrine tumors - a systematic review and meta-analysis.
Non-functional pancreatic neuroendocrine tumors (NF-PNET) are rare neoplasms being increasingly diagnosed. Surgical treatment or expectant management are both suggested for small NF-PNETs. The aim of this study was to evaluate the outcome of surveillance strategy for small NF-PNETs. A systematic search was performed up to March 2016 in MEDLINE, EMBASE and the Cochrane Library according to the PRISMA guidelines. Data was pooled using the random-effects model. Nine articles including 344 patients with sporadic and 64 patients with MEN1 related NF-PNET were selected. Tumor growth was observed in 22% and 52%, development of metastases were reported on 0% and 9%, and rate of secondary surgical resection was 12% and 25% in patients with sporadic or MEN1 related NF-PNETs, respectively. All metastases (1 distant, 4 nodal) were reported by a single study in patients with MEN1. Reason for secondary surgery was tumor growth in half of patients undergoing surgery. Expectant management of small asymptomatic, sporadic, NF-PNETs could be a reasonable option in highly selected patients. However, the level of evidence is low and longer follow-up is needed to identify patients could benefit from upfront surgery instead of expectant treatment.


Mouse mast cell sensitization with human IgG and allergen.
The heterologous binding of human IgG to mouse peritoneal mast cells was studied in vitro. The specific percentage of mast cell degranulation after treatment with sera heated for 2 hours at 57 degrees C was determined. These sera were obtained from normal or allergic patients, skin test positive to grass mix or dust, and then challenged separately with each allergen. The results show a high performance of degranulation by anti-human IgG and a direct correlation between skin test positivity and high degranulation values.


Polypropylene/Polyaniline Nanofiber/Reduced Graphene Oxide Nanocomposite with Enhanced Electrical, Dielectric, and Ferroelectric Properties for a High Energy Density Capacitor.
This work demonstrates a ternary nanocomposite system, composed of polypropylene (PP), redoped PANI (r-PANI) nanofibers, and reduced graphene oxides (RGOs), for use in a high energy density capacitor. r-PANI nanofibers were fabricated by the combination methods of chemical oxidation polymerization and secondary doping processes, resulting in higher conductivity (σ≈156 S cm(-1)) than that of the primarily doped PANI nanofibers (σ≈16 S cm(-1)). RGO sheets with high electron mobility and thermal stability can enhance the conductivity of r-PANI/RGO (σ≈220 S cm(-1)) and thermal stability of PP matrix. These findings could be extended to combine the advantages of r-PANI nanofibers and RGO sheets for developing an efficient means of preparing PP/r-PANI/RGO nanocomposite. When the r-PANI/RGO cofillers (10 vol %) were added to PP matrix, the resulting PP/r-PANI/RGO nanocomposite exhibited high dielectric constant (ε'≈51.8) with small dielectric loss (ε″≈9.3×10(-3)). Furthermore, the PP/r-PANI/RGO nanocomposite was used for an energy-harvesting device, which demonstrated high energy density (Ue≈12.6 J cm(-3)) and breakdown strength (E≈5.86×10(3) kV cm(-1)).


Genomic Insights Into A Novel, Alkalitolerant Nitrogen Fixing Bacteria, Azonexus sp. Strain ZS02.
Alkaline environments represent a significant challenge to the growth of micro-organisms. Despite this, there are a number of alkaline environments which contain active microbial communities. Here we describe the genome of a diazotrophic, alkalitolerant strain of Azonexus, which was isolated from a microcosm seeded with hyperalkaline soils resulting from lime depositions. The isolate has a genome size 3.60 Mb with 3431 protein coding genes. The proteome indicated the presence of genes associated with the cycling of nitrogen, in particular the fixation of atmospheric nitrogen. Although closely related to Azonexus hydrophilus strain d8-1 by both 16S (97.9%) and in silico gDNA (84.1%) relatedness, the isolate demonstrates a pH tolerance above that reported for this strain. The proteome contained genes for the complete Na+/H+ antiporter (subunits A to G) for cytoplasmic pH regulation; this may account for the phenotypic characteristics of this strain which exhibited optimal growth conditions of pH 9 and 30°C.


[Should metal alloy discs be used for patch testing in suspected metal implant intolerance reaction?].
Intolerance reactions to metal implants may be caused by metal allergy. However, prior to implantation, patch testing should not be done in a prophylactic-prophetic approach. Pre-implant patch testing should only be performed to verify or exclude metal allergy in patients with a reported respective history. In the case of implant-in particular arthroplasty-related complications like, for example, pain, effusion, skin changes, reduced range of motion, or loosening, orthopedic-surgical differential diagnostics should be performed first. Allergological workup of suspected metal implant allergy should be done with the DKG baseline series which contains nickel-, cobalt- and chromium-preparations. Various studies assessing the usefulness of metal alloy discs for patch testing proved that this approach does not give reliable information about metal allergy. Positive patch test reactions to the discs cannot be assigned to a specific metal within the disc alloy components. Furthermore, availability of such metal discs might be an invitation to uncritical testing. Accordingly, due to lack of benefit in comparison to patch testing with standardized metal salt preparations, we do not recommend patch testing with metal alloy discs.


Steroid hormones and medications that alter cancer risks.
Alkylating agents have caused acute nonlymphocytic leukemia (ANLL), probably bladder cancer, and possibly other solid tumors. Phenacetin also has enhanced risk of bladder cancer, and probably also carcinoma of the renal pelvis. Topical nitrogen mustard, potassium arsenite, tar ointments, and methoxsalene have been related to development of nonmelanotic skin cancers. Immunosuppression by azathioprine, usually with prednisone, has enhanced risks of non-Hodgkin's lymphomas, hepatobiliary cancers, and various mesenchymal tumors. Liver cancers have been reported in users of androgenic anabolic steroids, and both hepatic cell adenomas and carcinomas have been associated with use of combined oral contraceptives. These contraceptives reduce risks of endometrial and ovarian carcinomas. Estrogens increase risk of endometrial cancer. Exposure to diethylstilbestrol in utero can result in clear cell carcinomas of the vagina and cervix, and possibly testicular carcinomas.


Purulent pericarditis with tamponade caused by Salmonella enteritidis.
The incidence of purulent pericarditis has declined. However, mortality remains high. We describe a case of purulent pericarditis with tamponade caused by Salmonella enteritidis, and emphasize the importance of early recognition, prompt institution of appropriate antibiotic therapy, and early surgical drainage for survival.


Validation of the parent and teacher SDQ in a clinical sample.
This study examines whether the German translation of the Strengths and Difficulties Questionnaire (SDQ) is a reliable and valid screening instrument and whether it is as effective a tool for clinical diagnostics and scientific applications as the CBCL/TRF. We examined 543 children and adolescents (147 girls and 396 boys) with ages ranging from 5 to 17 years and correlated the results of the parent and teacher SDQ as well as the CBCL/TRF with clinical diagnoses. Furthermore, the adequacy of the scale structure of the SDQ was tested using confirmatory and exploratory factor analyses. It was demonstrated that the scales of the parent and teacher versions were sufficiently homogeneous (0.72-0.83). Correlations between SDQ scales and corresponding CBCL/TRF scales showed a high degree of congruence, while an exact replication of the original SDQ scale structure could also be achieved. Parent and teacher versions of both questionnaires presented with good validity, not only with regard to the discrimination between child psychiatric patients and a representative community sample, but also in the identification of different categories of disorders within the clinical sample. The parent and teacher SDQs proved to be valid and helpful questionnaires for use in the framework of a multi-dimensional behavioural assessment, and appear to be well suited for screening purposes, longitudinal monitoring of therapeutic effects, and scientific research purposes.


Ciprofloxacin-induced hypersensitivity vasculitis.
We describe a patient in whom cutaneous vasculitis appeared after 4 days of ciprofloxacin administration. On clinical examination, papular and purpuric lesions were limited to the left axillary zone of the thorax. Skin biopsy did not show the classic leukocytoclastic image but rather a mononuclear infiltrate of the vessel walls. Except a mild increase in inflammatory parameters, there were neither autoantibodies nor biological abnormalities, and the complement level was normal. These findings suggest that ciprofloxacin-induced vasculitis displays histopathological and serologic heterogeneity.


Design and racemic synthesis of conformationally restricted carbocyclic pyrimidine nucleoside analogs based on the structure of the L-nucleoside residue in heterochiral DNA.
Carbocyclic pyrimidine nucleoside analogs which have restricted glycosidic conformation at chi approximately 180 degrees were designed, based on the conformational features of the L-nucleotide residue in heterochiral DNA, and synthesized. The synthesis of (+/-)-carbocyclic 6,6'-O-cyclo-2'-deoxyuridine was achieved via bromination and subsequent intramolecular cyclization of carbocyclic 6'beta-hydroxy-2'-deoxyuridine. (+/-)-Carbocyclic 6,6'-O-cyclo-2'-deoxycytidine was synthesized from protected carbocyclic 6,6'-O-cyclo-2'-deoxyuridine via the 4-triazole intermediate.


The structure of executive functions in children: a closer examination of inhibition, shifting, and updating.
An increasing number of studies has investigated the latent factor structure of executive functions. Some studies found a three-factor structure of inhibition, shifting, and updating, but others could not replicate this finding. We assumed that the task choices and scoring methods might be responsible for these contradictory findings. Therefore, we selected tasks in which input modality was varied, controlled for baseline speed, and used both speed and accuracy scores, in order to investigate whether a three factor model with inhibition, shifting, and updating could still be replicated. In a group of 211 children, who were tested at the beginning of grade 1, at approximately 6 years of age, and again after 18 months, the best fitting model was not the three-factor model, but instead consisted of an updating factor and a combined inhibition and shifting factor, besides two baseline speed factors (verbal and motor). We argue that these results might indicate that the structural organization of executive functions might be different in children than in adults, but that there might also be an alternative explanation: the distinction in executive functions might not accurately represent cognitive structures but instead be a methodological artefact.


CHOLINESTERASE INHIBITION IN SPIDER MITES SUSCEPTIBLE AND RESISTANT TO ORGANOPHOSPHATE.
Evidence is provided that organophosphate resistance in a strain of spider mites is due to decreased sensitivity of its cholinesterase to organophosphates. The cholinesterase activity of the susceptible strain in vitro was three times that of the resistant strain of mites.


Renal transplantation during pregnancy--a case report.
A case of renal transplantation during the 12th week of pregnancy is presented. An episode of rejection 6 days after surgery was treated satisfactorily. At the 18th week, the patient showed a mild hypertension which was treated by hidralazine. At the 30th week a fetal pyelouretheral stenosis with celiciar dilatation was diagnosed and the mother had another rejection episode. At the 33rd week a cesarean section was performed after a pathological NST. Neonatal and maternal developmental courses were good.


Tissue factor pathway inhibitor (TFPI) antigen plasma level in patients with interstitial lung disease before and after heparin administration.
The extrinsic pathway is probably the predominant pathway in initiating blood coagulation in inflammatory lung diseases. Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor of factor VIIa/tissue factor in the presence of factor Xa. As it has been shown recently that TFPI plasma levels are increased under acute inflammatory conditions, we studied TFPI antigen plasma levels before and after injecting 20 IU/kg body weight of unfractionated heparin into 49 patients with different stages of sarcoidosis, into 9 with idiopathic pulmonary fibrosis, and into 15 normal controls. TFPI, before injecting heparin, was significantly increased in all sarcoidosis stages (stage I: 97.6 +/- 6.4 ng/mL; stage II: 116.2 +/- 11.9 ng/mL; stage III: 116.3 +/- 7.3 ng/mL) and in idiopathic pulmonary fibrosis (116.8 +/- 16.1 ng/mL), as compared to the control group (77.7 +/- 3.3 ng/mL). No correlation was found between the intensity of the activity of sarcoidosis, measured as BAL white cell count, and TFPI. Five minutes after heparin administration the rise in TFPI was lower, although not statistically significant, in all sarcoidosis stages than in controls. In contrast, idiopathic pulmonary fibrosis had a similar or even higher TFPI elevation than the control group. In sarcoidosis the elevated TFPI and the lower capacity by endothelial cells to release TFPI after heparin may represent a compensatory mechanism to prevent blood clotting and/or the endothelial cell dysfunction of the microvasculature in this condition. In contrast, the extensive mesenchymal cell proliferation present in idiopathic pulmonary fibrosis could explain our findings, as it has been shown that cultured human mesangial cells produce and release TFPI.


Cat-Scratch Lymphadenitis Presenting with Right Upper Arm and Axillary Masses: a Case Report Mimicking Lymphoma and Potential Diagnostic Pitfall.
Cat scratch disease (CSD) is an infectious disease caused by a cat's scratch, hard enough to break the skin's surface. Clinical manifestations include inflammatory lymphadenopathy and papular lesions at the site of the injury. However, it may be mistaken for a neoplasm-related process e.g., lymphoma due to its similar clinical presentation. To report a CSD case in an Indonesian male presenting with mass-like symptoms in the oncologic ward of our center. A 24-year-old male presented with painful and swelling masses in the right upper arm and right armpit for the last 4 months, enlarged progressively, and feverish for two days. Our initial differential diagnosis was lymphoma by history and routine physical examination, however. The patient reported a history of sleeping with his cat and recently experiencing a cat bite. We conducted the ultrasonography and lymph node biopsy to establish the final diagnosis and it was revealed to be related to CSD. The patient was treated with lymphadenectomy and azithromycin 500 mg bd for 7 days. The patient was completely treated with no additional complaints after two weeks of follow-up. The differential diagnosis for CSD is relatively broad, including active infection, an ongoing inflammatory process, or a metastatic process; hence, thorough diagnostic approaches should be made in approaching CSD cases to avoid the pitfall or mistreatment in advance.


A quinoline alkaloid rich Quisqualis indica floral extract enhances the bioactivity.
A volatile alkaloid quinoline-4-carbonitrile (QCN) was isolated from the floral extract of Quisqualis indica. Major compounds were trans-linalool oxide (1.0, 4.5%), methyl benzoate (1.0, 4.0%), 2,2,6-trimethyl-6-vinyl-tetrahydropyran-3-one (7.4, 17.8%), 2,2,6-trimethyl-6-vinyl-tetrahydropyran-3-ol (1.0, 1.2%), (E,E)-α-farnesene (29.1, 16.1%), QCN (5.7, 1.3%) in live and picked flowers, respectively. Flower compositions were altered due to change in enzymatic reaction at the time of picking. Some rearrangements of oxygenated terpenoids occurred in the process of hydrodistillation to obtain essential oil. Chemical synthesis of QCN and its selectively reduced products derived from QCN were prepared through green reaction process. The catalytic modification of QCN has produced quinoline-4-methylamine; the later compound has shown enhanced bio-activities. QCN and floral extract (absolute) have shown potential anti-inflammatory and antioxidant activities. Besides, floral absolute has shown significant anti-inflammatory and antioxidant activities due to improved QCN (19.7%) content to synergize amongst terpenoids and benzenoids as compared to the essential oil with 1.1% of QCN.


Outpatient Extraperitoneal Single-Port Robotic Radical Prostatectomy.
To assess the safety and feasibility of extraperitoneal single-port robotic assisted laparoscopic radical prostatectomy using the da Vinci SP robotic platform for same-day surgery. Extraperitoneal single-port robotic prostatectomy (ESRP) using the da Vinci SP platform was performed on 60 patients with clinically localized prostate cancer and no prior definitive therapy. An enhanced recovery protocol was used in the perioperative period and minimal to no opiates were used in these patients. Preoperative, perioperative, and postoperative data were collected in a prospectively maintained institutional review board approved database and evaluated in a retrospective fashion. Mean operative time was 198 minutes and mean estimated blood loss was 179 mL. No patients required blood transfusion and there were no intraoperative complications. Pain at discharge was 0-1 in 37% of patients. Forty-five patients (75%) were discharged home the day of surgery, including patients with all surgical start times. When excluding patients that were planned for an overnight stay preoperatively or patients whose surgery finished after 6 PM, 88% of patients were discharged home the day of surgery and 96% were discharged within 24 hours of surgery. Median length of stay was 4.2 hours. Fourty-eight percent of patients required 0-1 pads at 30 days postoperatively in patients with 30 day follow data (n = 58) and 76% of patients reported requiring 0-1 pads per day by 90 days postoperatively (n = 37). ESRP using the da Vinci SP platform can be performed safely and reproducibly as a same-day outpatient surgery with minimal to no opiate use, excellent pain control, and acceptable short term functional and oncological outcomes.


Severe cytological atypia (large cell change) in focal nodular hyperplasia with numerous mallory bodies. A benign (adaptive) change?
Focal nodular hyperplasia (FNH) is a benign hepatocellular lesion composed of hyperplastic appearing hepatocytes arranged in nodules separated by fibrous septa that usually form a central stellate scar. Rare lesions that show unusual cytological or architectural features were reported as variants of focal nodular hyperplasia. We present the morphological features of a case of FNH with severe cytological atypia (so-called large cell change) in a 73-year-old man. In addition to diffuse cytological atypia, Mallory hyaline bodies were found in almost all lesional cells. This rare variant of FNH should be differentiated from other neoplastic lesions, in particular from the fibrolamellar variant of hepatocellular carcinoma.


[Basement membranes: general aspects, role in odontogenesis].
Basement membranes are interposed between epithelial and mesenchymal cells and surround muscles. This particular extracellular matrix was first considered as a static structure, assuming cohesiveness of adjacent tissues. However during the last ten years, basement membranes were shown to be continuously renewed and to present compositional and structural modifications. During development changing basement membranes play important roles during histomorphogenesis and cytodifferentiation and are involved in normal and pathological behavior of adult tissues.


Comparison of culture methods for isolation of nontuberculous mycobacteria from surface waters.
The environment is the likely source of most nontuberculous mycobacteria (NTM) involved in human infections, especially pulmonary, skin, and soft tissue infections. In order to measure the prevalence of NTM in different aquatic ecosystems, we tried to standardize the culture methods used for surface water testing since many procedures have been described previously. Cultivation of mycobacteria requires long-term incubation in rich media and inactivation of rapidly growing microorganisms whose growth impedes observation of mycobacterial colonies. Consequently, the two criteria used for evaluation of the methods examined were (i) the rate of inhibition of nontarget microorganisms and (ii) the efficiency of recovery of mycobacteria. We compared the competitive growth of Mycobacterium chelonae and M. avium with nontarget microorganisms on rich Middlebrook 7H11-mycobactin medium after treatment by several chemical decontamination methods that included acids, bases, detergent, or cetylpyridinium chloride (CPC) with and without an antibiotic cocktail, either PANTA (40 U/ml polymyxin, 4 microg/ml amphotericin B, 16 microg/ml nalidixic acid, 4 microg/ml trimethoprim, and 4 microg/ml azlocillin) or PANTAV (PANTA plus 10 microg/ml vancomycin). Our results showed that treatment for 30 min with CPC (final concentration, 0.05%) of water concentrated by centrifugation, followed by culture on a rich medium supplemented with PANTA, significantly decreased the growth of nontarget microorganisms (the concentrations were 6.2 +/- 0.4 log(10) CFU/liter on Middlebrook 7H11j medium and 4.2 +/- 0.2 log(10) CFU/liter on Middlebrook 7H11j medium containing PANTA [P < 0.001]), while the effect of this procedure on NTM was not as great (the concentrations of M. chelonae on the two media were 7.0 +/- 0.0 log(10) CFU/liter and 6.9 +/- 0.0 log(10) CFU/liter, respectively, and the concentrations of M. avium were 9.1 +/- 0.0 log(10) CFU/liter and 8.9 +/- 0.0 log(10) CFU/liter, respectively). We propose that this standardized culture procedure could be used for detection of NTM in aquatic samples.


[Rotator cuff rupture: definition, establishing the diagnosis and therapy].
The rotator cuff tear is an extremely common disorder in the general as well in the orthopaedic praxis. The etiology is multifactorial with intrinsic and extrinsic factors. Clinical assessment of the patient is important for an exact diagnosis and an individual treatment plan. The treatment options of full thickness tears include conservative as well as operative procedures. Over the last years, modified techniques have improved the results of rotator cuff reconstruction.


Molecular epidemiology and clinical significance of Corynebacterium striatum isolated from clinical specimens.
This study investigated the clinical epidemiology, antimicrobial susceptibility, and molecular epidemiology of Corynebacterium striatum isolates. An observational study was conducted at a university hospital in the Republic of Korea from August to December 2016. All subjects were patients who tested positive for C. striatum clinically. Clinical data were analyzed to evaluate the microbiological and genotypic characteristics of C. striatum strains. Sixty-seven C. striatum isolates recovered from non-duplicated patients were characterized. Patients were classified into three groups according to the infection type: nosocomial infection (71.6%), health care-associated infection (8.7%), and community-acquired infection (18.8%). The most common clinical specimens were urine (35.8%) and skin abscesses (32.8%). Fifty-two (77.6%) isolates showed multidrug resistance, defined as resistance to ≥3 different antibiotic families. All strains were susceptible to vancomycin and linezolid. Resistance to other antibiotics varied: penicillin (n=65; 97.0%), ampicillin (n=63; 94.0%), cefotaxime (n=64; 95.5%), and levofloxacin (n=61; 91.0%). Phylogenetic analysis identified all 16 S rRNA gene sequences of the 67 isolates as those of C. striatum, where 98%-99% were homologous to C. striatum ATCC 6940. In multilocus sequence typing for internal transcribed spacer region, gyrA, and rpoB sequencing, the most predominant sequence types (STs) were ST2, ST3, ST6, and ST5. C. striatum isolates may cause opportunistic infections associated with nosocomial infections through horizontal transmission. The presence of multidrug resistance and intra-hospital dissemination implicate C. striatum isolates as a potential target pathogen for infection control and antimicrobial stewardship programs.


Graphene-Embedded Hydrogel Nanofibers for Detection and Removal of Aqueous-Phase Dyes.
A facile route to graphene/polymer hydrogel nanofibers was developed. An aqueous dispersion of graphene (containing >40% bilayer graphene flakes) stabilized by a functionalized water-soluble polymer with phenyl side chains was successfully electrospun to yield nanofibers. Subsequent vapor-phase cross-linking of the nanofibers produced graphene-embedded hydrogel nanofibers (GHNFs). Interestingly, the GHNFs showed chemical sensitivity to the cationic dyes methylene blue (MB) and crystal violet (CV) in the aqueous phase. The adsorption capacities were as high as 0.43 and 0.33 mmol g-1 s-1 for MB and CV, respectively, even in a 1.5 mL s-1 flow system. A density functional theory calculation revealed that aqueous-phase MB and CV dyes were oriented parallel to the graphene surface and that the graphene/dye ensembles were stabilized by secondary physical bonding mechanisms such as the π-π stacking interaction in an aqueous medium. The GHNFs exhibited electrochemical properties arising mainly from the electric double-layer capacitance, which were applied in a demonstration of GHNF-based membrane electrodes (5 cm in diameter) for detecting the dyes in the flow system. It is believed that the GHNF membrane can be a successful model candidate for commercialization of graphene due to its easy-to-fabricate process and remarkable properties.


Resolution of daytime and night-time respiratory symptoms but persistent sleep apnea in severe asthma with the add-on of benralizumab.
The relationship between asthma and obstructive sleep apnea (OSA) is a widely debated topic in the scientific literature with the controversy surrounding the bi-directional nature of the correlation. We report the case of a 59-year-old male being affected by severe allergic eosinophilic asthma and severe OSA (apnea-hypopnea index [AHI] 32 ev·hr-1). Due to a clinical worsening of asthma (aggravation of dyspnea, chest constriction and night-time respiratory symptoms), despite the optimal therapy for asthma and recurrent administration of systemic corticosteroids, we have added-on treatment with benralizumab (monoclonal anti-interleukin 5 antibody). After eight months, the patient reported an improvement in asthma control (asthma control test [ACT]= 25 points), in pulmonary function and a good control of nocturnal symptoms of both diseases (i.e., wheezing, snoring, etc.). Then, the follow up polysomnography (PSG) was performed resulting in a high reduction of OSA severity (~18% AHI) even if obstructive events persisted and almost resolution of nocturnal hypoxemia. So, a trial with positive airway pressure (PAP) was proposed to the patient, who declined. In consideration of our experience, we suggest that the nocturnal profile of patients with severe asthma should be always studied by a sleep investigation to prevent the negative effects of interaction with OSA. However, further studies on larger samples are needed to better understand the pathophysiological mechanisms underlying the beneficial effects of benralizumab on obstructive events during sleep.


Cyclic dipeptide based cell-penetrating peptidomimetics for effective DNA delivery.
An unnatural CDP-amino acid (kd) is used in the design and synthesis of novel cell penetrating peptidomimetic (Kkd-5). The balanced cationic nature and structural rigidity of Kkd-5 resulted in serum stability, non-toxicity to cells, and interaction with membrane and DNA, all of which facilitated efficient cellular uptake and DNA delivery.


Endothelial Cyp26b1 restrains murine heart valve growth during development.
Endothelial cells (ECs) are critical to proper heart valve development, directly contributing to the mesenchyme of the cardiac cushions, which progressively transform into mature valves. To date, investigators have lacked sufficient markers of valve ECs to evaluate their contributions during valve morphogenesis fully. As a result, it has been unclear whether the well-characterized regional differentiation of valves correlates with any endothelial domains in the heart. Furthermore, it has been difficult to ascertain whether endothelial heterogeneity in the heart influences underlying mesenchymal zones in an angiocrine manner. To identify regionally expressed EC genes in the heart valves, we screened publicly available databases and assembled a toolkit of endothelial-enriched genes. We identified Cyp26b1 as one of many endothelial enriched genes found to be expressed in the endocardium of the developing cushions and valves. Here, we show that Cyp26b1 is required for normal heart valve development. Genetic ablation of Cyp26b1 in mouse embryos leads to abnormally thickened aortic valve leaflets, which is due in part to increased endothelial and mesenchymal cell proliferation in the remodeling valves. In addition, Cyp26b1 mutant hearts display ventricular septal defects (VSDs) in a portion of null embryos. We show that loss of Cyp26b1 results in upregulation of retinoic acid (RA) target genes, supporting the observation that Cyp26b1 has RA-dependent roles. Together, this work identifies a novel role for Cyp26b1 in heart valve morphogenesis and points to a role of RA in this process. Understanding the spatiotemporal expression dynamics of cardiac EC genes will pave the way for investigation of both normal and dysfunctional heart valve development.


Ensemble averaging and multiple statistical testing of EMG activities of cyclically repeated body motions. A tool for muscle function analysis in experimental and clinical orthopaedics.
Coupled with suitable computerized signal recording and processing methods surface electromyography can be a powerful tool for the analysis of muscle activity in specific body movements. It can be used for this purpose in experimental and in clinical diagnostic orthopaedics as well as in physiotherapy. We describe in this paper a motion analysis system comprising this feature. It has been employed for the diagnosis of the basic angular kinematics and muscle function in human gait and other cyclically repeatable movements of the human locomotive system. Changes in the temporal characteristics of the movements and the muscle activity due to changed physical or experimental conditions can be systematically investigated this way. Such changes can be the result of surgical and/or conservative orthopaedic therapy, a long term physiotherapeutic program, or modified walking conditions as in experimental orthopaedics. They are displayed and validated by signal ensemble averaging and subsequent multiple statistical testing (e.g. by a suitably adapted Bonferroni criterion). The efficiency of the system is demonstrated by an exemplary gait analysis of selected kinematic and muscular effects caused by an experimental simulation of a leg length inequality.


First stretching overtone of BiH3: an extreme local-mode case for XH3-type molecule?
The first stretching overtone region of short-lived, formerly inaccessible BiH3 near 3405 cm(-1) has been measured by Fourier-transform infrared spectroscopy with a resolution of 0.0066 cm(-1). Only the 2nu1(A1)/nu1+nu3(E) band system has been observed. Rotational analysis, with transitions reaching J'max=14, has revealed almost perfect local-mode behavior for the upper states denoted as (200A1/E) in the local-mode notation. Ratios of vibration-rotation interaction parameters q(eff)/alpha(eff)(BB) and r(eff)/alpha(eff)(BC), and the appropriate rotational constant differences, are in good agreement with theoretical local-mode limit values. A simple stretching vibrational model reproduces the observed vibrational term values well, and the potential parameters obtained are close to true values.


Selective Inhibition of STAT3 with Respect to STAT1: Insights from Molecular Dynamics and Ensemble Docking Simulations.
STAT3 protein, which is known to be involved in cancer development, is a promising target for anticancer therapy. Successful inhibitors of STAT3 should not affect an activity of closely related protein STAT1, which makes their development challenging. The mechanisms of selectivity of several existing STAT3 inhibitors are not clear. In this work, we studied molecular mechanisms of selectivity of 13 experimentally tested STAT3 inhibitors by means of extensive molecular dynamics and ensemble docking simulations. It is shown that all studied inhibitors bind to the large part of the protein surface in an unspecific statistical manner. The binding to the dimerization interface of the SH2 domain, which is usually considered as the main target region, is not energetically preferable. Binding in this region is remarkably similar for STAT1 and STAT3 proteins and cannot explain experimentally observed selectivity toward STAT3. We propose a new mechanism of selectivity called "selectivity by distraction" for existing STAT3 inhibitors. This mechanism is based on equilibrium statistical partitioning of inhibitor molecules between protein domains. The unspecific binding of inhibitors to the DNA-binding and the coil-coil domains is stronger in STAT1 in comparison to STAT3 while the energies of their binding to SH2 domains are comparable. This "distracts" inhibitor molecules from the SH2 domain of STAT1 and leads to higher effective concentration of inhibitors in the vicinity of the SH2 domain of STAT3.


[Effects of GnRH analogues on MAPK pathway in rat Leydig cells].
To investigate the effects of GnRH analogues GnRHa and GnRHant on the MAPK pathway in rat Leydig cells. Rat Leydig cells were primarily cultured for 24 hours in vitro and serum-starved for 2 hours, followed by treatment with GnRHa (10(-7) mol/L) or GnRHant (10(-6) mol/L) for 0, 5, 15, 30, 60 and 90 minutes, with the 0 min group as the control. Then the protein levels of phosphorylated ERK (p-ERK) and phosphorylated p38 (p-p38) were detected by Western blot, and that of p-ERK determined by the same means after co-incubation of GnRHa or GnRHant with the PKC inhibitor GF109203X at 1, 5, 10 and 20 micromol/L. After stimulation of the Leydig cells with GnRHa or GnRHant for different times, the protein level of p-p38 showed no significant difference from that of the control group (P > 0.05). Then the Leydig cells were treated with GF109203X at different concentrations for 20 minutes and with addition of GnRHa for another 10 minutes. The level of p-ERK was significantly decreased (P < 0.05) by GF109203X at 10 and 20 micromol/L. Compared with the control, the p-ERK expression was increased by 65% at 15 minutes (P < 0.05) in the GnRHant stimulation group, by 81% (to the peak) at 30 minutes (P < 0.05), began to fall at 60 minutes, and returned to the base level at 90 minutes. The p-ERK level exhibited no significant difference from that of the control (P > 0.05) after treatment of the Leydig cells with different concentrations of GF109203X for 20 minutes and then with GnRHant for 30 minutes. The ERK MAPK activation induced by GnRHa depends on the PKC pathway, but not that induced by GnRHant. The p-38 MAPK pathway may not be involved in the effect of GnRH analogues on rat Leydig cells.


Magnesium lithospermate B improves renal function via the kallikrein-prostaglandin system in rats with renal failure.
The effect of magnesium lithospermate B on the renal responses of rats with renal failure was investigated in the presence and absence of pretreatment with the kallikrein inhibitor, aprotinin. Magnesium lithospermate B caused a marked increase in the levels of the renal functional parameters (glomerular filtration rate, renal plasma flow and renal blood flow), accompanied by significant increases in urinary prostaglandin excretion (increases of prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion by 82% and 36%, respectively). The urinary excretion of kallikrein was also increased following magnesium lithospermate B administration. However, pretreatment with aprotinin abolished the renal function-facilitating action of magnesium lithospermate B concomitantly with a markedly increased urinary excretion of prostaglandin E2, 6-keto-prostaglandin F1 alpha and kallikrein. These results suggest that the kallikrein-kinin-prostaglandin B.


Reducing the patient fall rate in a rural health system.
In healthcare facilities, patient falls have been a major contributing factor associated with patient injuries that result in increased costs and increased length of stay. Recent actions by the Department of Health and Human Services, enacted through the Department of Medicare and Medicaid Services, now hold healthcare facilities financially responsible for injury to patients that result from falls (CMS Hospital Acquired Conditions). Because of these rulings, costs associated with patient falls are now a greater threat to the survival of rural healthcare facilities. The rate of patient falls at Wise Regional Health System was unacceptably high. As a result of statistically analyzing the demographics of previous fall victims, and initiating additional interventions for identified patients, Wise Regional Health System has been successful in drastically decreasing their inpatient fall rate.


Role of renin-angiotensin and kallikrein-kinin systems on the mechanism of the hypotensive effects of converting enzyme inhibitor, alacepril.
In four patients with essential hypertension and one patient with renovascular hypertension, decreases in blood pressure and plasma angiotensin II levels, and increases in plasma renin activity and plasma kinin levels were observed during eight days of alacepril treatment. Significant correlations between the changes in mean arterial pressure and those in plasma angiotensin II or kinin levels were observed positively or negatively, respectively, in the essential hypertensives. These findings suggest that the hypotensive effect of alacepril might be caused mainly by a decrease in plasma angiotensin II levels and, at least in part, by an increase in plasma kinin levels.


Viruses infecting marine brown algae.
Viruses infecting algal hosts possess large double-stranded DNA as genomes. We have recently identified a family of viruses specific for filamentous brown algae. In contrast to the better known Chlorella viruses with their lytic infection cycle, marine brown algal viruses latently occur in their host cells and are induced to multiply in response to a variety of external stimuli such as change in light and temperature. Here, I summarize the known properties of this family of viruses and discuss their taxonomic classification.


[Cell biology and function of eosinophilic granulocytes in immunologic inflammation].
In recent years, increasing evidence has accumulated to suggest that the eosinophil represents a potent cytotoxic effector cell which plays a key role in the pathogenesis of pulmonary diseases as well as other human disorders. Beside contributing to antiparasitic host defense, eosinophils can prove detrimental to a number of host organs and tissues via release of their preformed basic proteins as well as de novo generated lipid mediators or oxygen radicals. Eosinophil effector functions are stimulated by certain lipid mediators and cytokines released by other cells in the course of active disease. In addition to their effector functions, eosinophils may have other functions in immune responses. Synthesis and expression of class II proteins of the major histocompatibility complex (MHC) may enable eosinophils to serve as antigen-presenting cells, i.e. to the antigens that appear at mucosal surfaces. In addition to collaborative interactions with lymphocytes, CD4-expressing eosinophils may elaborate cytokines that can effect cells within their tissue milieu. In conclusion, the evolving understanding of eosinophils indicates that eosinophils may not only serve as end-stage effector cells but also interact cooperatively with other cellular tissue elements in related diseases.


Selective bond breaking mediated by state specific vibrational excitation in model HOD molecule through optimized femtosecond IR pulse: a simulated annealing based approach.
The selective control of O-H/O-D bond dissociation in reduced dimensionality model of HOD molecule has been explored through IR+UV femtosecond pulses. The IR pulse has been optimized using simulated annealing stochastic approach to maximize population of a desired low quanta vibrational state. Since those vibrational wavefunctions of the ground electronic states are preferentially localized either along the O-H or O-D mode, the femtosecond UV pulse is used only to transfer vibrationally excited molecule to the repulsive upper surface to cleave specific bond, O-H or O-D. While transferring from the ground electronic state to the repulsive one, the optimization of the UV pulse is not necessarily required except specific case. The results so obtained are analyzed with respect to time integrated flux along with contours of time evolution of probability density on excited potential energy surface. After preferential excitation from [line]0, 0> ([line]m, n> stands for the state having m and n quanta of excitations in O-H and O-D mode, respectively) vibrational level of the ground electronic state to its specific low quanta vibrational state ([line]1, 0> or [line]0, 1> or [line]2, 0> or [line]0, 2>) by using optimized IR pulse, the dissociation of O-D or O-H bond through the excited potential energy surface by UV laser pulse appears quite high namely, 88% (O-H ; [line]1, 0>) or 58% (O-D ; [line]0, 1>) or 85% (O-H ; [line]2, 0>) or 59% (O-D ; [line]0, 2>). Such selectivity of the bond breaking by UV pulse (if required, optimized) together with optimized IR one is encouraging compared to the normal pulses.


Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway.
Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.


[Effectiveness of anterior cruciate ligament reconstruction with personalized femoral locator based on apex of deep cartilage].
To investigate the effectiveness of anterior cruciate ligament (ACL) reconstruction assisted by personalized femoral locator based on the apex of deep cartilage (ADC) combined with patient imaging data. Between January 2021 and January 2022, a total of 40 patients with primary ACL rupture were selected and randomly divided into study group (ACL reconstruction assisted by personalized femoral locator based on ADC) and control group (ACL reconstruction assisted by intraoperative fluoroscopy and traditional femoral locator), with 20 cases in each group. There was no significant difference in gender, age, body mass index, affected side, cause of injury, and preoperative International Knee Documentation Committee (IKDC) score, Lyshlom score, and Tegner score between the two groups ( P>0.05). IKDC score, Lyshlom score, and Tegner score were used to evaluate the functional recovery of the affected knee before operation and at 3, 6, and 12 months after operation. CT scan and three-dimensional reconstruction were performed before and after operation to measure the horizontal distance from ADC to the anterior cartilage margin (L) and the horizontal distance from ADC to the center of the femoral canal (I), and the anteroposterior position of the bone canal (R) was calculated by I/L; the distance from the center to the distal cartilage margin (D) was measured on the two-dimensional cross section; the R value and D value were compared between the two groups. The operation time of the study group was significantly less than that of the control group [ MD=-6.90 (-8.78, -5.03), P<0.001]. The incisions of the two groups healed by first intention, and no complication such as intra-articular infection, nerve injury, and deep vein thrombosis of lower limbs occurred. There was no significant difference in the R value and D value between the preoperative simulated positioning and the actual intraoperative positioning in the study group [ MD=0.52 (-2.85, 3.88), P=0.758; MD=0.36 (-0.39, 1.11), P=0.351]. There was no significant difference in the actual intraoperative positioning R value and D value between the study group and the control group [ MD=1.01 (-2.57, 4.58), P=0.573; MD=0.24 (-0.34, 0.82), P=0.411]. The patients in both groups were followed up 12-13 months (mean, 12.4 months). The IKDC score, Lysholm score, and Tegner score of the two groups increased gradually with time, and there were significant differences between pre- and post-operation ( P<0.05). There was no significant difference in the scores between the two groups at each time point after operation ( P>0.05). The personalized femoral locator based on ADC can accurately assist the femoral tunnel positioning in ACL reconstruction, which can shorten the operation time when compared with traditional surgical methods, and achieve satisfactory early effectiveness.


Perforation peritonitis due to gastrointestinal cryptococcosis as an initial presentation in an AIDS patient.
A 30-year-old woman underwent exploratory laparotomy for perforation peritonitis. Primary repair of the jejunal perforation was performed. The ulcer edge biopsy revealed Cryptococcus. Subsequently ELISA was reactive for HIV-1 antibody. This report describes a rare case of cryptococcal jejunal perforation, which was the initial presentation in an AIDS patient.


Local anaphor licensing in an SOV language: implications for retrieval strategies.
Because morphological and syntactic constraints govern the distribution of potential antecedents for local anaphors, local antecedent retrieval might be expected to make equal use of both syntactic and morphological cues. However, previous research (e.g., Dillon et al., 2013) has shown that local antecedent retrieval is not susceptible to the same morphological interference effects observed during the resolution of morphologically-driven grammatical dependencies, such as subject-verb agreement checking (e.g., Pearlmutter et al., 1999). Although this lack of interference has been taken as evidence that syntactic cues are given priority over morphological cues in local antecedent retrieval, the absence of interference could also be the result of a confound in the materials used: the post-verbal position of local anaphors in prior studies may obscure morphological interference that would otherwise be visible if the critical anaphor were in a different position. We investigated the licensing of local anaphors (reciprocals) in Hindi, an SOV language, in order to determine whether pre-verbal anaphors are subject to morphological interference from feature-matching distractors in a way that post-verbal anaphors are not. Computational simulations using a version of the ACT-R parser (Lewis and Vasishth, 2005) predicted that a feature-matching distractor should facilitate the processing of an unlicensed reciprocal if morphological cues are used in antecedent retrieval. In a self-paced reading study we found no evidence that distractors eased processing of an unlicensed reciprocal. However, the presence of a distractor increased difficulty of processing following the reciprocal. We discuss the significance of these results for theories of cue selection in retrieval.


Analysis of long-term human cytomegalovirus latency in vitro.
Human leukocyte interferon (IFN-alpha) and acyclovir (ACV) have been used to establish human cytomegalovirus (HCMV) latency in infected human embryo lung fibroblast (HEL-F) cells. HCMV latency was maintained for a short interval (less than 9 days) after removal of inhibitors by increasing the incubation temperature. We now report a model system in which HCMV latency has been dramatically extended. HEL-F cells pretreated with IFN-alpha (200 IU/ml) and ACV (300 microM) were infected with a low MOI of HCMV, and treated for 23 days with the same inhibitor combination at 37 degrees. Infectious HCMV and virus antigens were undetectable at the time of inhibitor removal and remained undetectable during continued incubation at 40.5 degrees. A minimum of 0.4% of the cell population, however, contained a virus genome that could be reactivated at the time of inhibitor removal; this value declined to 0.0005% after 77 days at 40.5 degrees. HCMV reactivation was achieved by maintaining the infected cells at 37 degrees after inhibitor removal or by decreasing the incubation temperature to 37 degrees at any time during maintenance at 40.5 degrees. The HCMV genome was analyzed by blot hybridization in latently infected cells 23 days after inhibitor treatment at 37 degrees or 4 days after inhibitor removal at 40.5 degrees. Although many HCMV-unique DNA genomic sequences were retained in HEL-F cultures after 23 days of inhibitor treatment, a significant reduction in retained HCMV sequences occurred after inhibitor removal and temperature shift to 40.5 degrees. The XbaI HCMV DNA fragments retained in the latently infected HEL-F cultures were present at a copy number of at least 0.5 copies per haploid cell genome equivalent.


Ion-unquenchable and thermally "on-off" reversible room temperature phosphorescence of 3-bromoquinoline induced by supramolecular gels.
Ion-unquenchable and thermally on-off reversible room temperature phosphorescence (RTP) can be induced by entrapping 3-bromoquinoline (3-BrQ) into supramolecular gels formed by the self-assembly of a sorbitol derivative (DBS). In comparison with conventional substrates inducing RTP, the gel state 3-BrQ/DBS can produce strong RTP due to the efficient restriction of the vibration of 3-BrQ. Notably, the rather inconvenient deoxygenation is no longer necessary in the preparation of 3-BrQ/DBS gels. The produced RTP was found to be very fast to reach stable, not depending on the standing time. As a reference, in the liquid state of 3-BrQ/sodium deoxycholate (NaDC), stable RTP can be observed after standing for 5 h. The investigation of RTP quenching indicates that the mechanism of RTP induced by DBS gels mainly involves the microenvironment in which 3-BrQ is located. 3-BrQ was entrapped in the hydrophobic 3D network structure of DBS gels, thereby restricting the motion and collision of 3-BrQ and avoiding RTP quenching and additionally quenching by ions. Furthermore, the RTP of 3-BrQ/DBS gels show an excellent "on-off" effect at 10 or 80 °C. This indicates that the solid DBS gel is beneficial for the preparation of RTP sensor devices.


Uterus transplants and their ethical implications.
Early experiments in womb transplants have increased interest in the possibility of performing this procedure in women who have no womb, usually for congenital reasons. The present article describes past experiments and summarises the most relevant reference documents before indicating the key ethical implications involved in womb transplants.


How much progress has been made in minimally invasive surgery for gastric cancer in Korea?: a viewpoint from Korean prospective clinical trials.
Gastric cancer is the most common cancer in Korea. Because the incidence of gastric cancer is still high even with early detection and because of developments in surgical instruments and technological advances, minimally invasive surgery has rapidly become an accepted treatment for gastric cancer in Korea. Many Korean gastric surgeons have contributed to the rapid adaptation of minimally invasive surgery for gastric cancer: not only the Korean Laparoscopic Gastrointestinal Surgery Study (KLASS) group, but also other expert surgeons after the 2000s. Thanks to their vigorous efforts involving active learning, education, workshops, academic communications, and international communications with active laparoscopic gastric surgeons in Korea, numerous results and well-designed large-scale clinical studies have been published or are actively ongoing, thus increasing its wide acceptance as an option for gastric cancer. Now, Korea has become one of the leading countries using minimally invasive surgery for the treatment of gastric cancer. This review article will summarize the current status and issues, as well as the clinical trials that have finished or are ongoing, regarding minimally invasive surgery for gastric cancer in Korea.


Synergistic Anticancer Effect of Paclitaxel and Noscapine on Human Prostate Cancer Cell Lines.
Paclitaxel is one of the most common chemotherapeutic drugs used for the treatment of prostate cancer. However, its current clinical utility has been limited due to numerous serious side effects and drug resistance. Noscapine is an antitussive opium alkaloid that showed antitumor activity against a variety of cancer while it has not exhibited severe side effects. This study investigates the anticancer activity of noscapine in combination with paclitaxel against two LNCaP and PC-3 human prostate cancer cell lines. LNCaP and PC-3 cells were treated with noscapine or paclitaxel or combination. Cell viability was determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test. Apoptosis was assessed by acridine orange/ ethidium bromide (AO/EB) staining. The mRNA expression of Bax, Bcl-2, AR, and PSA in the cellular response to treatments was investigated. MTT assay indicated the combination treatment of paclitaxel and noscapine significantly decreased viability compared to single-agent treatment and control groups. The results obtained with AO/EB double staining showed increased percentages of apoptotic cells in the presence of the combination of paclitaxel and noscapine. Furthermore, combinational treatment of paclitaxel and noscapine showed significant decrease in the mRNA expression of B-cell CLL/Lymphoma (Bcl-2) and increase in the mRNA expression of Bcl-2-associated X protein (Bax(, and Bax/Bcl-2 ratio in LNCaP and PC-3 cells (P<0.05.( The mRNA expression of androgen receptor (AR) and prostate specific antigen (PSA) decreased in paclitaxel and noscapine combination-treated of LNCaP cells (P<0.05). This study provides a novel concept of combination treatment of paclitaxel and noscapine to improve efficiency in human prostate cancer treatment.


Discovery of LL-K8-22: A Selective, Durable, and Small-Molecule Degrader of the CDK8-Cyclin C Complex.
The CDK8-cyclin C complex is an important anti-tumor target, but unlike CDK8, cyclin C remains undruggable. Modulators regulating cyclin C activity directly are still under development. Here, a series of hydrophobic tagging-based degraders of the CDK8-cyclin C complex were designed, synthesized, and evaluated to identify the first dual degrader, LL-K8-22, which induced selective and synchronous degradation of CDK8 and cyclin C. Proteomic and immunoblot studies exhibited that LL-K8-22 significantly degraded CDK8 without reducing CDK19 and did not degrade other cyclin proteins except cyclin C. Moreover, LL-K8-22 showed enhanced anti-proliferative effects over its parental molecule, BI-1347, with potency increased by 5-fold in MDA-MB-468 cells. LL-K8-22 exhibited more pronounced effects on CDK8-cyclin C downstream signaling than BI-1347, suppressing STAT1 phosphorylation more persistently. RNA-sequencing analysis revealed that LL-K8-22 inhibited E2F- and MYC-driven carcinogenic transcriptional programs. Overall, LL-K8-22 is the first-in-class degrader of cyclin C and would be useful for studying the unknown functions of cyclin C.


Prevalence and implications of frailty in acute stroke: systematic review & meta-analysis.
frailty is common in older adults and associated with poor outcomes following illness. Although stroke is predominantly a disease of older people, our knowledge of frailty in stroke is limited. We aimed to collate the literature on acute stroke and frailty to estimate the prevalence of pre-stroke frailty and its associations with outcomes. paired researchers searched multidisciplinary electronic databases for papers describing frailty and acute stroke. We assessed risk of bias using Newcastle-Ottawa tools appropriate to study design. We created summary estimates of pre-stroke frailty using random effects models. We collated whether studies reported significant positive associations between frailty and clinical outcomes in adjusted models. we included 14 studies (n = 27,210 participants). Seven studies (n = 8,840) used a frailty index approach, four studies (n = 14,924) used Hospital Frailty Risk Scores. Pooled prevalence of pre-stroke frailty was 24.6% (95% confidence interval, CI: 16.2-33.1%; low quality evidence, downgraded due to heterogeneity, bias). Combining frailty and pre-frailty (nine studies, n = 23,827), prevalence of any frailty syndrome was 66.8% (95%CI: 49.9-83.7%). Seven studies were at risk of bias, from participant selection or method of frailty assessment. Pre-stroke frailty was associated with all adverse outcomes assessed, including longer-term mortality (positive association in 6 of 6 studies reporting this outcome; odds ratio: 3.75 [95%CI: 2.41-5.70]), length of admission (3 of 4 studies) and disability (4 of 6 studies). despite substantial heterogeneity, whichever way it is measured, frailty is common in patients presenting with acute stroke and associated with poor outcomes. This has implications for the design of stroke services and pathways.


Pilomyxoid Astrocytoma (PMA) Shows Significant Differences in Gene Expression vs. Pilocytic Astrocytoma (PA) and Variable Tendency Toward Maturation to PA.
Pilomyxoid astrocytomas (PMAs) manifest a more aggressive clinical course than pilocytic astrocytomas (PAs). Development of effective therapies demands a better biological understanding of PMA. We first conducted gene expression microarray analysis of 9 PMA and 13 PA from infra- and supratentorial sites. Unsupervised hierarchical clustering analysis demonstrated that tumors are grouped according to anatomic site, not diagnosis. Gene expression profiles were then contrasted between eight PMAs and six PAs, all supratentorial/hypothalamic/chiasmal. Clinical outcome of PMAs varied, with four out of four patients with diencephalic syndrome succumbing to disease, one of whom showed bulky metastatic leptomeningeal spread at autopsy, with bimodal maturation to PA in some areas and de-differentiation to glioblastoma in others. A surviving child has undergone multiple surgical debulking, with progressive maturation to PA over time. Ontology-enrichment analysis identified overexpression in PMAs of extracellular matrix and mitosis-related genes. Genes overexpressed in PMA vs. PA, ranked according to fold-change, included developmental genes H19, DACT2, extracellular matrix collagens (COL2A1; COL1A1) and IGF2BP3 (IMP3), the latter previously identified as an adverse prognostic factor in PMA and PA.


Ties that bind: the integration of plastid signalling pathways in plant cell metabolism.
Plastids are critical organelles in plant cells that perform diverse functions and are central to many metabolic pathways. Beyond their major roles in primary metabolism, of which their role in photosynthesis is perhaps best known, plastids contribute to the biosynthesis of phytohormones and other secondary metabolites, store critical biomolecules, and sense a range of environmental stresses. Accordingly, plastid-derived signals coordinate a host of physiological and developmental processes, often by emitting signalling molecules that regulate the expression of nuclear genes. Several excellent recent reviews have provided broad perspectives on plastid signalling pathways. In this review, we will highlight recent advances in our understanding of chloroplast signalling pathways. Our discussion focuses on new discoveries illuminating how chloroplasts determine life and death decisions in cells and on studies elucidating tetrapyrrole biosynthesis signal transduction networks. We will also examine the role of a plastid RNA helicase, ISE2, in chloroplast signalling, and scrutinize intriguing results investigating the potential role of stromules in conducting signals from the chloroplast to other cellular locations.


Quantitative axon terminal and end-plate morphology in amyotrophic lateral sclerosis.
An axon-end-plate double stain yielded more synaptic detail than the older methylene blue stain of the muscle biopsy specimen. Application of the double stain to amyotrophic lateral sclerosis confirmed earlier and well-known findings of denervation, abnormal end-plates, and axonal sprouting. Little new data emerged, however, and the sprouting index seemed to mislead. As in several previous investigations, muscle from normal human subjects showed evidence for at least past if not current denervation, substantiating the need for continued rigorous controls in such studies.


Japanese encephalitis virus manipulates lysosomes membrane for RNA replication and utilizes autophagy components for intracellular growth.
Japanese encephalitis virus is absolutely dependent on their host cells and has evolved various strategies to manipulate the cellular secretory pathways for viral replication. However, how cellular secretory pathways are hijacked, and the origin of the viral vesicles remains elusive during JEV replication. Here we show how JEV manipulates multiple components of the cellular secretory pathway, including autophagic machinery, to generate a superior environment for genome replication. We utilized double-strand RNA antibodies to label JEV RNA complex seeking the viral replication compartments and found that JEV genome replication takes place in lysosomes (LAMP1), not in autophagosomes (LC3). Subsequently, in situ hybridization results showed that viral RNAs (vRNAs) of JEV strongly colocalized with LAMP1. What surprised us was that JEV vRNAs markedly colocalized with LC3, indicating that autophagy plays an active role in JEV replication. Interestingly, we found that JEV utilized autophagic components for intracellular growth in an autophagy-dependent manner and the fusion of autophagosome-lysosome plays a positive role in JEV post-RNA replication processes. Collectively, our findings demonstrate that JEV can manipulate cellular secretory pathway to form genome replication organelles and exploit autophagy components for intracellular growth, providing new insights into the life cycle of JEV and uncovering an attractive target for antiviral drugs.


Role of SNPs in the Biogenesis of Mature miRNAs.
Single nucleotide polymorphisms (SNPs) play a significant role in microRNA (miRNA) generation, processing, and function and contribute to multiple phenotypes and diseases. Therefore, whole-genome analysis of how SNPs affect miRNA maturation mechanisms is important for precision medicine. The present study established an SNP-associated pre-miRNA (SNP-pre-miRNA) database, named miRSNPBase, and constructed SNP-pre-miRNA sequences. We also identified phenotypes and disease biomarker-associated isoform miRNA (isomiR) based on miRFind, which was developed in our previous study. We identified functional SNPs and isomiRs. We analyzed the biological characteristics of functional SNPs and isomiRs and studied their distribution in different ethnic groups using whole-genome analysis. Notably, we used individuals from Great Britain (GBR) as examples and identified isomiRs and isomiR-associated SNPs (iso-SNPs). We performed sequence alignments of isomiRs and miRNA sequencing data to verify the identified isomiRs and further revealed GBR ethnographic epigenetic dominant biomarkers. The SNP-pre-miRNA database consisted of 886 pre-miRNAs and 2640 SNPs. We analyzed the effects of SNP type, SNP location, and SNP-mediated free energy change during mature miRNA biogenesis and found that these factors were closely associated to mature miRNA biogenesis. Remarkably, 158 isomiRs were verified in the miRNA sequencing data for the 18 GBR samples. Our results indicated that SNPs affected the mature miRNA processing mechanism and contributed to the production of isomiRs. This mechanism may have important significance for epigenetic changes and diseases.


No change in anterior chamber dimensions after femtosecond LASIK for hyperopia.
To compare the changes in anterior chamber volume (ACV), anterior chamber depth (ACD) and anterior chamber angle (ACA) before and 6 months after femtosecond laser in situ keratomileusis (LASIK) for hyperopia using the Pentacam HR device. A total of 24 eyes of 24 consecutive hyperopic patients undergoing femtosecond LASIK were examined preoperatively and 6 months postoperatively. Anterior chamber volume; ACDs in the central, superior, inferior, nasal, and temporal quadrants; and ACA were measured using the Pentacam HR device. Comparisons of preoperative versus postoperative values were performed using paired Student t test. Linear regression analysis was performed to evaluate correlations between ACV change, central ACD change, age, and attempted maximum ablation depth. Preoperative and postoperative mean ACVs were 153.6 and 158.2 μL, respectively. Preoperative and postoperative mean ACDs were 2.81, 2.28, 2.53, 2.16, and 2.61 mm, and 2.84, 2.31, 2.54, 2.16, and 2.65 mm, respectively. Preoperative and postoperative mean ACAs were 33.3° and 32.0°, respectively. There were not statistically significant differences in ACV, ACDs, and ACA from preoperatively to 6 months after femtosecond LASIK (all P>0.05). The change of central ACD was correlated significantly with age at 6 months postoperatively (R=0.18, P=0.039). Anterior chamber profiles, including ACV, ACA, and central and peripheral ACDs did not significantly change after femtosecond LASIK for hyperopia.


Influence of commercial sanitizers on lipopolysaccharide production by Salmonella Enteritidis ATCC 13076.
The effect of typical sanitizers on the composition and toxicity of lipopolysaccharides (LPSs) produced by Salmonella Enteritidis ATCC 13076 was analyzed. Salmonella Enteritidis was propagated up to the late exponential phase in the presence of commercial sanitizing solutions. LPS was extracted and derivatized with trifluoroacetylation, and gas chromatography-mass spectrometry analysis and the chromogenic Limulus amoebocyte lysate assay were used to assess the ultrastructure and toxicity of the LPS. The viability and debris formation during growth were evaluated to verify the bactericidal and bacteriostatic effects of the sanitizers and to assess sanitizer effects on LPS formation. The LPSs produced were quantified at 1.7 x 10(4), 1.2 x 10(4), 3.6 x 10(3), and 9.6 x 10(4) [KDO] x OD(620nm)(-1) for the controls and the organisms grown in the presence of a chlorinated sanitizer, a heavy-duty alkaline cleaner, and a phenolic hand wash solution, respectively. In response to these treatments, the short-chain polysaccharide fractions of the LPSs in the Salmonella Enteritidis cells increased. This finding suggests that this organism increases the low-molecular-weight fraction of the LPS in relation to the high-molecular-weight fraction to survive these unfavorable conditions. The cumulative change in the LPS in response to the sanitizers influenced the toxicity of the LPS; however, this change could not be related to an individual compound within any of the assessed fractions.


Statistical approach to discovery of factors impacting on emergence of blood cancers in iran.
Cancer is now the main cause of increasing mortality throughout the world. Minor alterations in the cell cycle which are inherited and not removed by apoptosis are important risk factors. Blood cancers are asmong the types which most readily cause death. Here in this study, usual but important factors such as age, gender, Rh and ABO blood typing, weight, and platelet counts are analyzed for impact on blood cancers. Frequencies and distributions, correlations and chi-square test were utilized in order to clarify the perspective of important factors. Our statistical results show males and females to have same risk in blood cancer but A blood type (40%) along with positive Rh (73%) had the highest risk. Low platelet counts are related to more than 80% of cases. Obesity has a statistically ignorable role in blood cancer prevalence. The fact that blood cancer cases increase during the second decade of life (45.7%) which might be because of involvement of maturation processes.


Relationship between physico-chemical characteristics and potential toxicity of PM10.
PM10 was sampled at a suburban location affected by traffic and industry in the north of Spain. The samples were analysed to determine the chemical components of PM10 (organic and elemental carbon, soluble chemical species and metals). The aim of this study was to assess the toxicity of PM10 in terms of the bulk analysis and the physico-chemical properties of the particles. Total carbon, sulphates, ammonium, chlorides and nitrates were found to be the major constituents of PM10. The contribution of the last of these was found to increase significantly with PM10 concentration (Pearson coefficient correlation of 0.7, p-value < 0.001). Individual airborne particles were characterised morphologically and chemically via a combination of Scanning Electron Microscopy and Energy-Dispersive X-ray spectroscopy (SEM-EDX). The subsequent image analysis revealed C-rich particles with shapes that pointed to combustion processes. Moreover, carbonaceous particles seemed to act as vehicles for sulphur compounds and metals (S, Na, Fe, Ca, Mg, K, Al, Mn, Zn and Cu). Coarse particles were found to be mainly constituted by crustal material and marine and carbonaceous particles. Although most of the studied individual particles in PM10 samples (86.0%) had a diameter within the 0.1-2.5 μm range, 1.8% of them had sizes lower than 0.1 μm 40.2% of the total studied particles were estimated to be inhaled and deposited in the human respiratory tract; 12.3% of these particles would reach the deepest zones, thereby posing a major risk to human health.


Sandpile models and random walkers on finite lattices.
Abelian sandpile models, both deterministic, such as the Bak, Tang, Wiesenfeld (BTW) model [P. Bak, C. Tang, and K. Wiesenfeld, Phys. Rev. Lett. 59, 381 (1987)] and stochastic, such as the Manna model [S.S. Manna, J. Phys. A 24, L363 (1991)] are studied on finite square lattices with open boundaries. The avalanche size distribution P(L)(n) is calculated for a range of system sizes, L. The first few moments of this distribution are evaluated numerically and their dependence on the system size is examined. The sandpile models are conservative in the sense that grains are conserved in the bulk and can leave the system only through the boundaries. It is shown that the conservation law provides an interesting connection between the sandpile models and random-walk models. Using this connection, it is shown that the average avalanche sizes <n>(L) for the BTW and Manna models are equal to each other, and both are equal to the average path length of a random walker starting from a random initial site on the same lattice of size L. This is in spite of the fact that the sandpile models with deterministic (BTW) and stochastic (Manna) toppling rules exhibit different critical exponents, indicating that they belong to different universality classes.


[Efficacy and safety of inhaled drugs].
In the paper the foundations are presented of current inhalation therapy, particularly of that applied in childhood. The problems are discussed, concerning deposition of aerosols in the tracheobronchial tree achieved by various methods of aerosol generation. Various factors affecting the bioavailability of the inhaled drugs are defined. Particular attention is paid to the problems of safety of inhaled corticosteroid therapy, stability of the inhaled drugs and their influence on the pulmonary surfactant.


Sequence complexity of cDNA transcribed from a diverse mRNA population.
Mouse liver poly(A)+mRNA was reverse transcribed using oligo-p(dT) or random oligonucleotides as primers to yield cDNA about equal to the mass of the template RNA. The size profile of the oligo-p(dT)-primedd cDNA was similar to that of the template RNA. RNA or cDNA driven saturation annealing of labeled single copy genomic DNA (scDNA) showed that 2% of the scDNA was complementary in either case indicating the sequence complexity of cDNA was equivalent to that of the template mRNA. These results establish for the first time that cDNA represents essentially all of the sequence complexity of a diverse template RNA population in which individual mRNA species are present in vastly different concentrations. RNA driven hydridization of the cDNA showed that about 40% of the cDNA mass represents most of the sequence complexity of the template RNA. Also, kinetics of this hybridization indicate a complexity of 58,000 kb for the template RNA, a value similar to that obtained by scDNA hybridization. We conclude that appropriately characterized cDNA probes can be used to make valid qualitative and quantitative comparisons of the complex, infrequent class mRNAs of different cells and tissues.


A Simple Dual-pH Responsive Prodrug-Based Polymeric Micelles for Drug Delivery.
To precisely deliver drug molecules at a targeted site and in a controllable manner, there has been great interest in designing a synergistical drug delivery system that can achieve both surface charge-conversion and controlled release of a drug in response to different stimuli. Here we outline a simple method to construct an intelligent drug carrier, which can respond to two different pH values, therefore achieving charge conversion and chemical-bond-cleavage-induced drug release in a stepwise fashion. This drug carrier comes from the self-assembly of a block copolymer-DOX conjugate synthesized through a Schiff base reaction between poly(2-(diisopropylamino)ethyl methacrylate-b-poly(4-formylphenyl methacrylate-co-polyethylene glycol monomethyl ether methacrylate) (PDPA-b-P(FPMA-co-OEGMA)) and DOX. The surface charge of the BCP-DOX micelles reversed from negative to positive when encountering a weakly acidic environment due to the protonation of PDPA segments. In vitro cellular uptake measurement shows that the cellular uptake and internalization of the BCP-DOX micelles can be significantly enhanced at pH ∼ 6.5. Moreover, this drug carrier exhibits a pH-dependent drug release owing to the cleavage of the imine bond at pH < 5.5. With this dual-pH responsive feature, these micelles may have the ability to precisely deliver DOX to the cancer cells.


Recent developments and applications of capillary and microchip electrophoresis in proteomic and peptidomic analyses.
This review presents recent developments and applications of capillary and microchip electromigration methods in proteomics and peptidomics. Sample preparation methods as well as instrumental innovations in the coupling of these advanced electromigration methods with mass spectrometry detection employed in proteomic and peptidomic analyses are presented. Interesting applications of various capillary electromigration methods in bottom-up as well as top-down proteomics, including investigation of post-translational modifications of proteins are described. In addition, several examples of the use of capillary electromigration methods combined with mass spectrometry detection in clinical proteomics and peptidomics are demonstrated.


Renal vein plasma renin activity in patients with unilateral renovascular hypertension.
Plasma renin activity in the renal veins (V) or infrarenal inferior vena cavae (IVC) of 20 patients with unilateral renovascular hypertension (RVH) was measured to determine how renal vein renin ratio (RVRR) compares with renin index (V-IVC/IVC) as a predictor of curability of RVH. Although there was no significant difference between them in predicting curability, 3 out of 4 patients with hypersecretion of renin (V-IVC/IVC greater than or equal to 0.48) in the stenosed side with contralateral suppression (V-IVC/IVC less than or equal to 0) on the normal side were cured. In addition, 7 out of 11 patients with contralateral suppression irrespective of values of renin index in the stenosed side were also cured. On the other hand, only one out of 6 patients who had neither hypersecretion nor contralateral suppression was cured. These results reconfirm that significant renin secretion with or without contralateral suppression, or only contralateral suppression of renin is highly suggestive of curable RVH.


Racial and Ethnic Disparities in Hospital Readmissions After Delivery.
To examine 30-day readmission rates after vaginal and cesarean delivery by race-ethnicity and insurance status. We analyzed hospital discharge data contained in a statewide database maintained by the Connecticut Department of Public Health. Discharge data for patients admitted for vaginal delivery without complication (n=167,857) and cesarean delivery without complication (n=75,552) from 2005 to 2012 were analyzed using marginal logistic models for clustered data with generalized estimating equations. Results from logistic models indicated that 30-day readmission rates per 1,000 patients were significantly higher among black (28.9/1,000; confidence interval [CI] 25.5-32.7) and Hispanic women (21.4/1,000; CI 18.9-24.2) than among white women (12.9/1,000; CI 11.9-14.0) after cesarean delivery. Similarly higher rates of readmission were observed for black (14.6/1,000; CI 13.0-16.5) and Hispanic women (10.7/1,000; CI 9.6-12.0) relative to white women (7.5/1,000; CI 7.0-8.1) after vaginal delivery. Rates of 30-day readmission were significantly higher (odds ratio 1.27-1.30) among those covered by Medicaid. Controlling for patient socioeconomic status, comorbidities, and payer did not substantially reduce race and ethic differences in the odds of readmission. Significant racial and ethnic disparities in readmissions were observed for procedures related to childbirth using a statewide database capturing all payers across all acute care hospital settings. Compared with white women, black women were twice as likely and Hispanic women 40-50% more likely to be readmitted within 30 days of vaginal or cesarean delivery. II.


Protective effect of short-term thymoquinone administration on the central nervous system in cisplatin-induced neurotoxicity.
This study was performed to investigate the potential beneficial effects of thymoquinone (TQ) on brain tissue based on biochemical and histopathological analyses in cisplatin (CIS) treated rats with central nervous system (CNS) neurotoxicity. The rats were randomly divided into 4 groups with 8 rats in each group (n:8). Group 1: (Control), saline was administered for 3 days at a volume of 0.5 ml per day intraperitoneal (i.p.). Group 2: (CIS Group), one dose of CIS was administered (7 mg/kg i.p.). Group 3: (TQ Group), TQ was given at a dose of 5 mg/kg per day for 3 days (i.p.). Group 4: (CIS+TQ Group), one dose of 7 mg/kg was initiated half an hour before administration of CIS and one dose of 5 mg/kg per day was administered TQ i.p. for 3 days. Malondialdehyde levels were found to be statistically significantly higher in the CIS group compared to the control group. Degenerative changes observed in the CIS+TQ group were found to be milder than in the CIS group. In the CIS+TQ group, a statistically significant decrease in the severity of caspase-3 immunoreactivity was found when compared to the CIS group. It was found that the severity of neurofilament immunoreactivity monitored in neuronal extensions was similar in all groups. In the CIS+TQ group, the severity of tau protein's immunoreactivity was similar to that of the CIS-group. According to the results obtained in our study, beneficial effects were obtained in reducing neurotoxicity with short-term TQ application in rats treated with CIS treatment.


[The hyper IgE syndrome (Buckley syndrome)].
An exceptional case is reported of hyper IgE syndrome and membranoproliferative glomerulonephritis with onset in 1964. Renal disease, symptoms of hyper IgE syndrome and level of serum IgE were improved by a long-term cyclosporine treatment (3/5 mg/kg/day) with a follow-up of 4 years. The characteristics of the hyper IgE syndrome, described by Buckley in 1972 are given and the respective roles of IgE-BF, IL4 and interferon in the mechanism of increase in serum IgE is discussed.


Morphology of elastic poly(L-lactide-co-epsilon-caprolactone) copolymers and in vitro and in vivo degradation behavior of their scaffolds.
Very elastic PLCL [poly(L-lactide-co-epsilon-caprolactone), 50:50] copolymers were synthesized and extruded into porous tubular scaffolds (pore size 150 +/- 50 microm, porosity 90%) for the application to tissue engineering. The copolymers were basically random and amorphous. However, two T(g)'s (glass transition temperatures) were observed in dynamic mechanical thermal analysis and also in differential scanning calorimetry thermograms. Furthermore, microdomains (about 17 nm in size) were indicated on the small-angle X-ray scattering profile and finally confirmed by transmission electron microscopy. Therefore, the PLCL copolymer was probably composed of a soft matrix of mainly epsilon-caprolactone moieties and hard domains containing more L-lactide units to exhibit a rubberlike elasticity in virtue of the physically cross-linked structure. The smooth muscle cells seeded scaffolds were implanted into nude mice subcutaneously for up to 15 weeks to monitor the in vivo degradation. In addition, they were degraded in vitro in phosphate buffer solution (pH 7.4) for up to 1 year to compare the results each other. All the scaffolds degraded slowly in vivo and in vitro even in the form of a highly porous thin membrane. However, the degradation rate was somewhat faster for in vivo than for in vitro. This should be explained by enzymes that might have played a certain role in the degradation in the body. In addition, the epsilon-caprolactone moieties degraded faster than the L-lactide units did in these PLCL scaffolds, although their hydrophilicities are in the opposite order. This behavior appeared more prominently in the in vivo case. This should result from that the amorphous regions composed of mainly epsilon-caprolactone units might have been first attacked by water because water can penetrate into the amorphous regions easier than the hard domains containing more L-lactides.


Therapeutic options for external genital warts.
The primary goal of treatment for external genital warts (EGWs) is to eradicate visible lesions and address symptoms that may accompany them, but it does not address the underlying virus. Left untreated, warts may grow, remain the same, or spontaneously regress as a result of being cleared by the immune system. However, recurrence is common with or without treatment and may occur within 3 months of ending treatment in one-quarter to two-thirds of cases. Treatment options fall into two categories: provider or patient applied. Provider-based therapies include cryotherapy, trichloroacetic and bichloroacetic acid, electrocautery, surgical excision, and CO2 laser therapy. Patient-applied therapy choices include imiquimod and podophyllotoxin. Imiquimod 3.75% is a fairly new, patient-administered topical cream approved by Health Canada in 2011. Another recently approved patient-applied choice is sinecatechins, a green tea extract with immunomodulatory effects. Self-treatment options are attractive to patients because they offer privacy, convenience, and autonomy. In contrast, provider-administered therapies may boast increased precision (especially for areas that are hard to reach) and closer monitoring, which can be augmented by patient education and counseling. Available topical and surgical therapies vary widely in terms of cost, efficacy, adverse effects, dosage/frequency, and length of treatment. No one treatment is ideally suited to all patients or constitutes a gold standard. Treatment regimens must be tailored to each patient's needs and preferences. The health care provider's skills and experience will also factor into treatment decisions. In addition, the size, number, and location of lesions and whether the infection is new or recurrent will help guide the decision process toward the best treatment for a given patient.