Presence of several plasmids in the fungus Ascobolus immersus, and homologies with the linear plasmid pA1.
DNA analysis of several genetically unstable strains of the fungus Ascobolus immersus revealed the presence of at least seven different plasmids. These plasmids ranged from 2 to 20 kb in size, and showed homology to one of them, pA1. In 18 stocks directly isolated from nature, two-thirds harboured plasmids ranging from 3 to 17 kb. Plasmids with homology to pA1 had similar molecular masses (about 8.5 kb). A possible mechanism of plasmid formation from chromosomal DNA is discussed.


Update on the Role of Imaging in Staging of Common Pediatric Abdominal Tumors.
Neuroblastoma, Wilms tumor, and hepatoblastoma are the most common pediatric abdominal malignancies. Management of these diseases is a multidisciplinary process that continues to evolve based on the results of international collaborative trials and advances in understanding of tumor biology. Each of these tumors has unique characteristics and behavior which are reflected in their respective staging systems. It is important for clinicians involved in the care of children with abdominal malignancies to be familiar with current staging guidelines and imaging recommendations. This article reviews the current role of imaging in the management of these common pediatric abdominal malignancies, with emphasis on initial staging.


Homolog Pairing at the Push of a Button.
Homologous chromosomes pair in somatic cells in Drosophila, but how this occurs is poorly understood. In this issue of Developmental Cell, Viets et al. (2019) show that proteins and chromatin structure mediate pairing and argue against a DNA sequence-based mechanism.


Carotenoid pigments of genus Rhodococcus.
A study of carotenoid pigments of the genus Rhodococcus was carried out. According to carotenes contained, Rhodococcus species were divided into three groups: the first group of Rhodococcus luteus, R. coprophilus, R. lentifragmentus, and R. maris, which formed beta-carotene; the second group of R. equi, R. rubropertinctus, R. aichiensis, R. sputi, R. chubuensis, R. obuensis, R. bronchialis, R. roseus, R. rhodochrous, R. rhodnii, and R. terrae, which formed gamma-carotene-like substance; and the third group of R. aurantiacus, which formed neither carotene. Other carotenoid pigments were different according to the species.


Endovascular therapy for penetrating ulcers of the infrarenal aorta.
We sought to investigate the short- and mid-term results of the endovascular repair of infrarenal abdominal penetrating aortic ulcers (aPAUs). Patients with infrarenal aPAUs treated by endovascular means between March 2004 and June 2012 were recruited. Pre-interventional imaging included computed tomography (CT) or CT angiography. Endoprostheses were chosen and deployed according to standard elective endovascular aneurysm repair anatomical requirements. Endpoints included 30-day survival, in-hospital mortality, 1-year PAU-related mortality, 1-year all-cause mortality, freedom from death and freedom from cumulative complication and interventions. Statistically, the Kaplan-Meier method was applied. Nineteen patients (18 men, median age 70 years (interquartile range, IQR = 59-75)) suffering aPAUs (n = 29, infrarenal = 25) were detected. The median co-morbid severity scoring was 1.0 (IQR = 0.4-1.4). The median follow-up period was 33 months (IQR = 8-51.5). Furthermore, 94.7% of patients had hypertension. Fourteen patients (73.7%) had symptoms, including four of them admitted with shock from large-contained PAU rupture. Endoluminal stent grafting was successfully delivered in all patients. In-hospital mortality was 10.5%. Two patients required secondary interventions (10.5%). The 30-day survival, 1-year PAU-related mortality and 1-year all-cause mortality were 94.7%, 89.5% and 89.5%, respectively. Freedom from death and freedom from cumulative complications and interventions was 86.4% and 86.4%, 78.9% and 78.9%, and 67.9% and 71.2% at 12, 24 and 36 months, respectively. Urgent and elective endovascular repair of aPAUs can be achieved with high technical success. The significant co-morbid status of the treated patients is illustrated in the considerable in-hospital mortality and underlines the advantage of such treatment over open surgical repair.


Calculating potential doubling time using monoclonal antibodies specific for two halogenated thymidine analogues.
A new flow cytometric technique that allows for two-incorporated thymidine analogues to be measured simultaneously and independently has been used to improve the accuracy of in vivo cell kinetic estimates, i.e., the length of S-phase (TS) and potential doubling time (Tpot). The analogues chlorodeoxyuridine and iododeoxyuridine were injected at different times into mice bearing the mouse mammary tumor MCaK. At different times after labeling, the tumors were harvested and prepared for three color flow cytometric analysis of DNA, chlorodeoxyuridine, and iododeoxyuridine. Control experiments showed that similar estimates of Tpot were obtained from each label when administered singly, or as staggered pulses. Comparisons were made between TS and Tpot calculated from a single label (single point), from the averaged result of the two labels from the same tumor (two point-ave), and from the simultaneous nonlinear fitting of the measured parameters from the two labels, from the same tumor (two point-fit). These estimates of TS and Tpot were then compared to reference values obtained by fitting the pooled measured parameters from all the tumors, that were labeled for different periods of time. While all of the methods resulted in similar mean estimates of TS and Tpot that were close to the reference values, the fewest assumptions, and the least variability in the results, were obtained using the two point-fit data. The estimation of Tpot using two thymidine analogues is more accurate than that obtained from a single label.


Uremia with low serum creatinine-an entity produced by marked creatinine secretion.
Two patients are presented who were uremic requiring dialysis despite steady state serum creatinine levels (Cr) of 4.0 and 4.4 mg percent. Their blood urea nitrogen/creatinine (BUN/Cr) ratios of 54 and 44 were shown to be due to excessive creatinine secretion and urea reabsorption. Evaluation of serum creatinine alone may occasionally give misleading information regarding the level of renal function. If clinical evidence of uremia is present while serum creatinine value is relatively low, measurement of glomerular filtration rate (GFR) by Na-iothalamate 125I (OIT) or inulin is essential.


Direct Aggression and the Balance between Status and Affection Goals in Adolescence.
Previous studies have shown that status goals motivate direct forms of interpersonal aggression. However, status goals have been studied mostly in isolation from affection goals. It is theorized that the means by which status and affection goals are satisfied change during adolescence, which can affect aggression. This is tested in a pooled sample of (pre)adolescents (N = 1536; 49% girls; ages 10-15), by examining associations between status goals and direct aggression and the moderating role of affection goals. As hypothesized, with increasing age, status goals were more strongly associated with direct aggression. Moreover, for older adolescents, status goals were only associated with aggression when affection goals were weak. These findings support the changing relationship between status goals and direct aggression during adolescence.


Design, synthesis, ADME characterization and antileishmanial evaluation of novel substituted quinoline analogs.
In vitro ADME characterization of the lead compound 1 identified for visceral leishmaniasis was undertaken and further structural analogs were synthesized for antileishmanial screening. Compound 1 was highly permeable in intestinal PAMPA model (31 × 10(-6)cm/s) and was moderately bound to mouse and human plasma proteins (% bound 85-95%), its blood to plasma concentration ratio was less than 1, but the compound was unstable in blood. Compound 1 was found to have no CYP450 liability with CYP2C9, 2C19, 2D6 and 3A4. It showed inhibition with CYP1A2 with an IC50 value of 0.50 μM. Analogs of 1 were synthesized and subsequently characterized for in vitro activity against the intracellular form of Leishmania donovani. Resulting quinolines were found to have similar efficacy as 1 against the parasite. Compounds 8b and 8f were found to be the most active with IC50 values of 0.84 μM and 0.17 μM, respectively compared to 0.22 μM for compound 1. Of all the analogs tested, 8d was stable in hamster, mouse and human liver microsomes but lost the efficacy with an IC50 of 6.42 μM. Based on the in vitro efficacy and DMPK profile, compounds 8b and 8f seem the best candidates to be screened in further assays.


High-intensity focused ultrasound applied to the placenta using a toroidal transducer: a preliminary ex-vivo study.
To demonstrate in an ex-vivo model the feasibility of applying high-intensity focused ultrasound (HIFU) using a toroidal transducer for the creation of placental lesions. In this study we used a toroidal transducer, composed of 32 ring-shaped emitters with an ultrasound probe at the center, operating at a frequency of 2.5 MHz. We examined 45 human placentae, following either normal vaginal delivery or medical termination of pregnancy between 17 and 40 gestational weeks. First, the attenuation coefficients of 12 human placentae were measured and integrated into a numerical model for simulating HIFU lesions. Then, using acoustic parameters from this preliminary study, we performed ex-vivo experiments with 33 human placentae, each overlain with an animal abdominal wall to simulate the maternal wall. We created single HIFU lesions in 25 of these placentae, and a series of six juxtaposed lesions in eight, studying these both sonographically and macroscopically. Human placental attenuation coefficients of the 12 human placentae ranged from 0.072 to 0.098 Np/cm/MHz, according to gestational age. The 25 single HIFU lesions created had an average diameter of 7.1 ± 3.2 mm and an average depth of 8.2 ± 3.1 mm. The average diameter of the eight series of six juxtaposed HIFU lesions was 23.0 ± 5.0 mm and the average depth was 11.0 ± 4.7 mm. The average thickness of the abdominal walls was 10.5 ± 1.8 mm. No lesions or damage were observed in intervening tissues. This study demonstrates, using an ex-vivo model, the feasibility, reproducibility, harmlessness and effectiveness of HIFU applied to the human placenta.


The current status of clinics providing private practice cell therapy in Japan.
To clarify the current state of clinics in Japan that offer unproven cell therapies. Google searches were performed to collect and analyze what kind of clinics provide what kind of cell therapies. A total of 74 clinics and 247 cases of cell therapies were identified. Various cell therapies, including allograft, were provided not only to seriously ill patients but also to patients with other therapeutic options and healthy individuals. Although the practices revealed by our study seem to deviate from international standard, some of these can be construed as legal under the Japanese new act established in 2014. Considering many patients travel to foreign countries to seek therapy, more research from non-English-speaking countries is needed.


The Mycobacterium tuberculosis PPE protein Rv1168c induces stronger B cell response than Rv0256c in active TB patients.
Tuberculosis (TB) caused by Mycobacterium tuberculosis is a serious global health problem and is responsible for millions of deaths every year. For effective control of this dreadful disease, it is necessary to diagnose TB cases at the initial stages of infection. The serodiagnosis of disease represents simple, rapid and inexpensive method that can be used at the primary health care levels. In this study we have compared sensitivity of two PPE proteins of M. tuberculosis, i.e., Rv0256c and Rv1168c for their use as serodiagnostic markers in active tuberculosis patients. Employing a standardized enzyme immunoassay with these PPE proteins as candidate antigens we were able to successfully discriminate the TB patients' sera from the BCG-vaccinated healthy controls. Further, we observed that Rv1168c displayed higher sensitivity in detecting extrapulmonary and smear negative pulmonary TB cases which are difficult to diagnose by available diagnostic methods. Overall the study highlights that Rv1168c can be used as a potential serodiagnostic marker for the diagnosis of active tuberculosis disease.


Follow-up studies of suspicious choroidal nevi.
The fundus photographs and fluorescein angiograms of 255 consecutive cases of choroidal nevi were reviewed. Sixty-one cases (24%) were selected as suspicious on the basis of strict preestablished criteria including greatest single diameter, elevation, degree of disruption of the retinal pigment epithelium, and presence of subretinal fluid. Fifty of these 61 had adequate four-year follow-up. The remaining 194 cases, labeled as nonsuspicious, were usually small, relatively flat, slate-grey nevi which failed to meet the criteria for being suspicious. Of the 50 suspicious choroidal nevi followed four years, five (10%) showed photographic evidence of growth 4 to 30 months after the last examination. In contrast, none of the 194 nonsuspicious cases demonstrated growth. On the basis of these results, recommendations are made for the management of suspicious choroidal nevi.


Effects of bleomycin on kinetoplast DNA and nuclear DNA in Trypanosoma gambiense using in situ microfluorometry technique.
The effect of Bleomycin, an anti-tumour antibiotic, on either kinetoplast DNA(K-DNA) or nuclear DNA(N-DNA) in a single Trypanosoma gambiense cell was measured successfully utilizing the in situ microfluorometry technique. This microfluorometric assay clearly revealed that the relative fluorescence intensity (RFI) of K-DNA and N-DNA was greatly reduced by bleomycin, suggesting the occurrence of the single strand breaks in these DNAs. The present results have shown that bleomycin acts on N-DNA stronger than K-DNA at least in Trypanosoma gambiense. Microfluorometry technique can be employed valuably for studying the DNA damages of several anti-protozoan drugs.


Duration of Allergen Immunotherapy for Long-Term Efficacy in Allergic Rhinoconjunctivitis.
Subcutaneous and sublingual immunotherapy are effective for allergic rhinitis. An important question is whether allergen immunotherapy provides a sustained clinical effect after treatment cessation. In view of potential side effects, cost and the necessary patient commitment, long-term benefit is an important consideration for the recommendation of immunotherapy over standard pharmacotherapy. In this review, we analyse the existing evidence for long-term effects of both routes of administration in the context of double-blind, placebo-controlled, randomised clinical trials that included a follow-up phase of at least 1 year after treatment cessation. Overall, evidence suggests that 3 years of either subcutaneous or sublingual immunotherapy result in clinical benefit and immunological changes consistent with allergen-specific tolerance sustained for at least 2-3 years after treatment cessation. The data presented here support recommendations in international guidelines that both routes of administration should be continued for a minimum of 3 years. Gaps in the evidence remain regarding the long-term efficacy of immunotherapy for perennial rhinitis and studies performed in children.


"It's Worked Well for Me": Young Women's Reasons for Choosing Lower-Efficacy Contraceptive Methods.
To understand the diverse reasons why some young women choose contraceptive methods that are less effective at preventing pregnancy, including condoms, withdrawal, and emergency contraception pills, even when more effective contraceptive methods are made available to them. In-depth interviews with young women at family planning clinics in July-November 2016. Interview data were thematically coded and analyzed using an iterative approach. Two youth-serving family planning clinics serving predominantly Latinx and African American communities in the San Francisco Bay Area, California. Twenty-two young women ages 15-25 years who recently accessed emergency contraception to prevent pregnancy. None. Young women's experiences using different methods of contraception, with specific attention to methods that are less effective at preventing pregnancy. Young women reported having previously used a range of higher- and lower-efficacy contraceptive methods. In interviews, they described affirmative values that drive their decision to use lower-efficacy methods, including: a preference for flexibility and spontaneity over continual contraceptive use, an emphasis on protecting one's body, and satisfaction with the method's effectiveness at preventing pregnancy. Some young women described using a combination of lower-efficacy methods to reduce their pregnancy risk. Young women make contraceptive decisions on the basis of preferences and values that include, but are not limited to, effectiveness at preventing pregnancy. These reasons are salient in their lives and need to be recognized as valid by sexual health care providers to ensure that young women receive ongoing high-quality care.


Black carbon aerosol quantification over north-west Himalayas: Seasonal heterogeneity, source apportionment and radiative forcing.
Continuous measurements of Black Carbon (BC) aerosol mass concentrations were carried at Dehradun (30.33°N, 78.04°E, 700 m amsl), a semi-urban site in the foothills of north-westHimalayas, India during January 2011-December 2017. We reported both the BC seasonal variations as well as mass concentrations from fossil fuel combustion (BCff) and biomass burning (BCbb) sources. Annual mean BC exhibited a strong seasonal variability with maxima during winter (4.86 ± 0.78 μg m-3) followed by autumn (4.18 ± 0.54 μg m-3), spring (3.93 ± 0.75 μg m-3) and minima during summer (2.41 ± 0.66 μg m-3). Annual averaged BC mass concentrations were 3.85 ± 1.16 μg m-3 varying from 3.29 to 4.37 μg m-3 whereas BCff and BCbb ranged from 0.11 to 7.12 μg m-3 and 0.13-3.6 μg m-3. The percentage contributions from BCff and BCbb to total BC are 66% and 34% respectively, indicating relatively higher contribution from biomass burning as compared to other locations in India. This is explained using potential source contribution function (PSCF) and concentration weighted trajectories (CWT) analysis which reveals the potential sources of BC originating from the north-west and eastern parts of IGP and the western part of the Himalayas that are mostly crop residue burning and forest fire regions in India. The annual mean ARF at top-of-atmosphere (TOA), at surface (SUR), and within the atmosphere (ATM) were found to be -14.84 Wm-2, -43.41 Wm-2, and +28.57 Wm-2 respectively. To understand the impact of columnar aerosol burden on ARF, the radiative forcing efficiency (ARFE) was estimated and averaged values were -31.81, -91.63 and 59.82 Wm-2 τ-1 for TOA, SUR and ATM respectively. The high ARFE within the atmosphere indicates the dominance of absorbing aerosol (BC and dust) over Northwest Himalayas.


Testicular lymphoma: sonographic findings.
The sonographic findings in 2 patients diagnosed as having testicular lymphoma (subsequently surgically proven) are discussed. The diagnosis should be suspected when a hypoechoic mass is identified in the testicle.


Therapeutic inhibition of miR-155 attenuates liver fibrosis via STAT3 signaling.
Most chronic liver diseases progress to liver fibrosis, which, when left untreated, can lead to cirrhosis and hepatocellular carcinoma. MicroRNA (miRNA)-targeted therapeutics have become attractive approaches to treat diseases. In this study, we investigated the therapeutic effect of miR-155 inhibition in the bile duct ligation (BDL) mouse model of liver fibrosis and evaluated the role of miR-155 in chronic liver fibrosis using miR-155-deficient (miR-155 knockout [KO]) mice. We found increased hepatic miR-155 expression in patients with cirrhosis and in the BDL- and CCl4-induced mouse models of liver fibrosis. Liver fibrosis was significantly reduced in miR-155 KO mice after CCl4 administration or BDL. To assess the therapeutic potential of miR-155 inhibition, we administered an rAAV8-anti-miR-155 tough decoy in vivo that significantly reduced liver damage and fibrosis in BDL. BDL-induced protein levels of transforming growth factor β (TGF-β), p-SMAD2/3, and p-STAT3 were attenuated in anti-miR-155-treated compared with control mice. Hepatic stellate cells from miR-155 KO mice showed attenuation in activation and mesenchymal marker expression. In vitro, miR-155 gain- and loss-of-function studies revealed that miR-155 regulates activation of stellate cells partly via STAT3 signaling. Our study suggests that miR-155 is the key regulator of liver fibrosis and might be a potential therapeutic target to attenuate fibrosis progression.


Quantitative proteomic analysis of HIV-1 infected CD4+ T cells reveals an early host response in important biological pathways: protein synthesis, cell proliferation, and T-cell activation.
Human immunodeficiency virus (HIV-1) depends upon host-encoded proteins to facilitate its replication while at the same time inhibiting critical components of innate and/or intrinsic immune response pathways. To characterize the host cell response on protein levels in CD4+ lymphoblastoid SUP-T1 cells after infection with HIV-1 strain LAI, we used mass spectrometry (MS)-based global quantitation with iTRAQ (isobaric tag for relative and absolute quantification). We found 266, 60 and 22 proteins differentially expressed (DE) (P-value ≤ 0.05) at 4, 8, and 20 hours post-infection (hpi), respectively, compared to time-matched mock-infected samples. The majority of changes in protein abundance occurred at an early stage of infection well before the de novo production of viral proteins. Functional analyses of these DE proteins showed enrichment in several biological pathways including protein synthesis, cell proliferation, and T-cell activation. Importantly, these early changes before the time of robust viral production have not been described before.


Glycerol's contribution to lactate production outside of a glucose intermediate in fasting humans.
Glycerol is a well-recognized substrate for new glucose production via gluconeogenesis in the liver. However, its carbon contribution to the glycolytic intermediate lactate is not known in humans. Here we infused stable isotope tracers 13C3-glycerol and 6,6-D2-glucose into six metabolically healthy individuals after an overnight fast to study glycerol metabolism and measure glucose rate of appearance. Serum samples underwent liquid chromatography-mass spectrometry analysis. Glycerol and glucose rates of appearance were 2.21 ± 1.42 μmol/kg/min and 7.81 ± 1.15 μmol/kg/min, respectively. Under steady-state conditions, the 13C enrichment for lactate was significantly higher than that of glucose (2.90 ± 0.52% versus 1.53 ± 0.78%, p = 0.017), suggesting direct glycerol to lactate metabolism. The percentage of lactate derived from glycerol was also significantly higher than the percentage of glucose (13.88 ± 2.69% versus 6.50 ± 2.59%, p = 0.005). Given that lactate itself is a carbon source for gluconeogenesis and tricycarboxylic cycle intermediates, glycerol's ability to donate carbons to lactate may make it quantitatively more important to intermediary metabolism than currently appreciated.


Application of a DNA double labelling method for the flow cytometric analysis of recruitment of non-cycling cells in a mixed population of P and Q cells.
In this paper we describe the application of a non-radioactive DNA double labelling and staining method to an analysis of cell proliferation kinetics by flow cytometry, aimed at the direct measurement of recruitment rates in cell cultures. The method is based on the application of two halogenated deoxyuridines: iododeoxyuridine (IdUrd) and chlorodeoxyuridine (CldUrd) which are incorporated into DNA synthesizing cells. By applying two commercially available monoclonal antibodies both deoxyuridines can be detected separately. To measure recruitment all proliferating cells in a plateau phase culture were labelled first with IdUrd applied during a time interval approximately equal to the cell cycle time. Subsequently, recruitment induced by a medium change was analysed by flow cytometric assessment of incorporation of CldUrd in cells which had not taken up IdUrd. Experiments designed to determine the toxicity of continuous labelling with IdUrd in different concentrations and of pulse labelling with CldUrd showed that there was no effect on the progression of cells through the cell cycle. The aim of this study is to test the sensitivity of the procedure to detect changes in proliferation kinetics, in particular the entrance of resting cells into the S phase. Although the cell culture model used is very simple, the results demonstrate clearly that a low rate of recruitment can be detected. It is suggested that the procedure described here is specific and sensitive enough to quantify changes in cell proliferation in tumours induced by various treatments and has advantages over other methods, which measure recruitment indirectly, or directly by using two radioactive thymidines.


[The applicability of results].
The ultimate aim of the critical reading of medical literature is to use the scientific advances in clinical practice or for innovation. This requires an evaluation of the applicability of the results of the studies that have been published, which begins with a clear understanding of these results. When the studies do not provide sufficient guarantees of rigor in design and analysis, the conditions necessary for the applicability of the results are not met; however, the fact that the results are reliable is not enough to make it worth trying to use their conclusions. This article explains how carrying out studies in experimental or artificial conditions often moves them away from the real conditions in which they claim to apply their conclusions. To evaluate this applicability, the article proposes evaluating a set of items that will enable the reader to determine the likelihood that the benefits and risks reported in the studies will yield the least uncertainty in the clinical arena where they aim to be applied.


Processed skin surface images acquired by acoustic impedance difference imaging using the ultrasonic interference method: a pilot study.
To clarify the potential of a novel system using the acoustic impedance difference imaging (AIDI) method for diagnosis of skin disorders, we used it on a coin and swine skin. An ultrasound wave with a central frequency of 20 MHz, emitted from a fused quartz rod with a diameter of 1.25 mm, was focused on the surface of the coin and skin samples. The difference in acoustic impedance was determined by the reflection-type interference-based acoustic impedance measurement method. The processed data were produced as greyscale images on which the maximum measured amplitudes were mapped. We applied the method to a coin. Swine skin, burned and covered with an acrylic sheet with a thickness of 0.2 mm (a few times the half-wavelength) to eliminate the undulations of the skin surface, was employed to obtain processed images from which undulation data were excluded. All the processed images obtained corresponded almost exactly with the magnified optical ones. In the processed images of swine skin, a marked difference was found after the burning procedure. The processed images obtained using the AIDI method reflected not only the undulations but also other information such as elasticity. In conclusion, our system using AIDI has the potential to become a useful modality for the diagnosis of skin disorders.


Hemolytic uremic syndrome caused by enteroviral infection.
A 4-year-old boy presented with enteroviral infection complicated with atypical hemolytic uremic syndrome (aHUS). Enterovirus RNA was detected by reverse transcription polymerase chain reaction (RT-PCR) of both blood and kidney biopsy specimens. A survey of the complement system did not reveal a specific complement defect. Supportive therapy with blood components transfusion, plasma therapy, and immunosuppressants was administered, however, renal function did not recover. The results of this report demonstrate that the enterovirus is the cause of aHUS.


An integrated network pharmacology approach reveals that Darutigenol reduces inflammation and cartilage degradation in a mouse collagen-induced arthritis model by inhibiting the JAK-STAT3 pathway.
Darutigenol (DL) is a natural active product derived from the Chinese herbal medicine Sigesbeckia glabrescens (Makino) Makino. It is administered as a traditional Chinese medicine (TCM) to dispel rheumatism, benefit the joints, and detoxify. However, its potential mechanism in the treatment of rheumatoid arthritis (RA) remains unknown. The objectives of this research were to determine the effects and elucidate the modes of action of DL on RA-related joint inflammation. Network pharmacology and molecular docking were used to screen and validate candidate DL targets for RA treatment, respectively. A DBA/1 mouse rheumatoid arthritis model was induced with bovine type II collagen. Intragastric DL administration was followed by the calculation of the clinical arthritis index. A section of the ankle joint was excised and stained and the pathological changes in it were observed. Enzyme-linked immunosorbent assays (ELISA) and western blotting (WB) were used to clarify the mechanisms of DL in RA treatment. DL effectively attenuated the inflammation, mitigated the articular cartilage degradation, and bone erosion, and alleviated the inflammatory joints associated with RA. Network pharmacology screened six key targets of DL while molecular docking revealed that it docked well with its protein targets. The DL treatment group presented with significantly less ankle joint redness and swelling, a lower arthritis index scores and serum and bone marrow supernatant IL-6 levels, more complete ankle joint surfaces, and less synovial inflammation, cartilage degradation, and bone erosion than the collagen-induced arthritis (CIA) group. The DL treatment also substantially downregulated the Janus kinase (JAK)1, JAK3, matrix metalloproteinase (MMP)2, MMP9, and phospho-signal transducer and activator of transcription (p-STAT)3 proteins in the joints. To the best of our knowledge, the present work was the first to demonstrate that DL has significant anti-inflammatory efficacy and reduces cartilage degradation and bone erosion. It also demonstrated that the anti-RA effect of DL may be explained by its ability to inhibit joint inflammation and reduce articular cartilage degradation through the interleukin (IL)-6/JAK1,3/STAT3 axis and downregulate MMP2 and MMP9. Hence, DL might play a therapeutic role in a mouse RA model.


Chemical communication: conductors and insulators of screw-sense preference between helical oligo(aminoisobutyric acid) domains.
(1)H NMR studies quantify the abilities of achiral amino acids to communicate a left-handed screw-sense preference from one helical Aib(4) domain to another: certain quaternary amino acids (e.g. Ac(6)c) act as effective conductors of conformational preference while others (e.g. diphenylglycine) acts as insulators.


Evaluation of unplanned interruptions in radiotherapy treatment schedules.
One of the major radiobiological interests has been to maximize the effectiveness of the time-dose relationship in the clinical setting. Current explorations include altered fractionation schedules, multiple daily fractions and hypofractionation. Patient compliance to standard radiotherapy treatment schedules is taken for granted. To evaluate the true rate of compliance, the charts of all new patients treated from July 1, 1984 through June 30, 1985 were reviewed. The overall incidence of unplanned interruptions was 54% (361/668). The frequency of interruptions is significantly higher in patients treated to the primary site as compared to those treated for metastasis (59.8% and 35.6% respectively). The duration of the interruptions varied: 12.7% of the patients missed only 1 day, 25% missed 2 to 5 days, 38% had interruptions totalling 6-15 days, and in 24% the total exceeded 15 days. The most frequent cause of the unplanned interruptions was a rest resulting from unusually adverse tissue reactions (46.8%-169/361). Although this study has documented that unplanned interruptions are a major problem, the impact on local control and survival cannot be determined from our data. A retrospective review of multi-institutional studies such as those conducted by the Patterns of Care or RTOG might show that one of the major causes of failure is unplanned interruptions.


Heart transplantation and left ventricular assist device therapy: two comparable options in end-stage heart failure?
Heart transplantation is the only curative therapy for chronic heart failure, and it plays an important role in the treatment of chronic heart failure with a survival rate of approximately 50% of all patients after 10 years. This has to be kept in mind when alternative therapies enter into our daily routine in treating this patient population. However, the shortage of appropriate donor organs and the expanding pool of patients waiting for heart transplantation have led to growing interest in alternative strategies, particularly in left ventricular assist device (LVAD) therapy. With growing clinical experience and continued technical advances, continuous-flow pumps are evolving as a bridge to transplantation or as a destination therapy for advanced heart failure. Nevertheless, the importance of this new indication of chronic cardiac support compared to heart transplantation is still completely open and the object of controversial ongoing discussion. This review (1) describes the clinical use and long-term outcome of a currently available miniaturized LVAD in the context to the standard of care-heart transplantation, (2) provides an outlook of the ongoing process of further optimization of LVADs, and (3) comments on the challenges with assist devices as alternatives to transplantation with a 5-year outlook.


Experimental studies on etiology of portal hypertension in allergic aspect.
To elucidate the mechanism of portal hypertension seen as a symptom of so-called Banti's syndrome (idiopathic portal hypertension), observation was made of rising of the portal pressure experimentally induced in sensitized rabbits. Intraintestinal injection of the same antigen as used for the sensitization resulted in elevation of the portal pressure. This phenomenon appears to be attributable to antigen-antibody reaction caused by the injected antigen absorbed from the intestine and entered thereby into the portal system while maintaining its antigenicity. From the phenomenon also, the site of the antigen-antibody reaction is estimated to be limited at least to the hepatic level. The portal pressure-rising phenomenon observed following intraintestinal introduction of antigen may suggest the possibility of entrance of the orally introduced antigen to the portal system, emphasizes importance of alimentary factors in the genesis of this syndrome.


Equilibrium ligand binding to the human erythrocyte sugar transporter. Evidence for two sugar-binding sites per carrier.
Equilibrium [3H]cytochalasin B binding to class I sites of human red cell membranes (the sugar transporter) was examined in the presence and absence of intracellular or extracellular sugars known to interact with the transport system. D-Glucose, a transported sugar, is without effect on cytochalasin B binding when present in the extracellular medium but is an effective inhibitor of binding when present within the cell. Ethylidene glucose and maltose (reactive but nontransported sugars) inhibit cytochalasin B (CCB) binding when present either outside or inside the red cell. Inhibition by intracellular sugar (Si) is of the simple, linear competitive type. Inhibition by extracellular sugars (So) is more complex; the Kd(app) for cytochalasin B binding increases in a saturable fashion with [So]. These observations are compared with the predictions of the one-site, alternating conformer model and the two-site model for substrate binding to the sugar transporter, X. The experimental results are inconsistent with the one-site model but are explained by a two-site model in which the ternary complexes of So . X . Si or So . X . CCBi exist and where the binding sites for So and Si display negative cooperativity when occupied by nontransported substrate and little or no cooperativity when occupied by the transported species, D-glucose.


Delivery of reprogramming factors into fibroblasts for generation of non-genetic induced pluripotent stem cells using a cationic bolaamphiphile as a non-viral vector.
Protein delivery allows a clinical effect to be directly realized without genetic modification of the host cells. We have developed a cationic bolaamphiphile as a non-viral vector for protein delivery application. The relatively low toxicity and efficient protein delivery by the cationic bolaamphiphile prompted us to test the system for the generation of induced pluripotent stem cells (iPSCs) as an alternative to the conventional vector-based genetic approach. Studies on the kinetics and cytotoxicity of the protein delivery system led us to use an optimized cationic bolaamphiphile-protein complex ratio of 7:1 (wt/wt) and a 3 h period of incubation with human fibroblasts, to ensure complete and non-toxic protein delivery of the reprogramming proteins. The reprogrammed cells were shown to exhibit the characteristics of embryonic stem cells, including expression of pluripotent markers, teratoma formation in SCID mice, and ability to be differentiated into a specific lineage, as exemplified by neuronal differentiation.


The heart rate response to succinylcholine in children: a comparison of atropine and glycopyrrolate.
To determine whether intravenous atropine and glycopyrrolate are equally effective in preventing succinylcholine-induced heart rate changes, we studied the heart rate during the first 78 seconds of anaesthesia in 40 children anaesthetized with either thiopentone, atropine (0.02 mg X kg-1) and succinylcholine (2 mg X kg-1), or thiopentone, glycopyrrolate (0.01 mg X kg-1) and succinylcholine (2 mg X kg-1). Each treatment group was divided into four subgroups which differed only in the interval (6, 10, 15, 20 seconds) between injection of atropine or glycopyrrolate and succinylcholine. During the 54 seconds after succinylcholine, the mean heart rate of each subgroup decreased transiently and then returned to the pre-induction heart rate or higher. There was no difference in either the magnitude or the duration of the decrease in heart rate or the subsequent increase in heart rate between respective subgroups. Bradycardia occurred in only two patients, both of whom received glycopyrrolate. We conclude that atropine (0.02 mg X kg-1) and glycopyrrolate (0.01 mg X kg-1) are equally effective in attenuating succinylcholine-induced changes in heart rate in children.


Effects of a dark-septate endophytic isolate LBF-2 on the medicinal plant Lycium barbarum L.
Dark septate endophytes (DSE) are ubiquitous root associated fungi; however, our understanding of their ecological function remains unclear. Here, we investigated the positive effect of a DSE fungus on its host plant Lycium barbarum L. A DSE isolate, LBF-2, isolated from the roots of L. barbarum, was inoculated onto the roots of plants, which were grown under greenhouse conditions for five weeks. The result of molecular analyses of internal transcribed spacer regions indicated that LBF-2 was 96% similar to Paraphoma chrysanthemicola. Melanized septate hyphae were observed in the root cortical cells of L. barbarum using a light microscope. Inoculation with LBF-2 increased the total biomass by 39.2% and also enhanced chlorophyll fluorescence. Inoculation increased the concentration of total chlorophyll by 22.8% and of chlorophyll a by 21.3%, relative to uninoculated controls. These data indicate that the LBF-2 isolate might be used to facilitate the cultivation of L. barbarum, which has medicinal applications.


Alternative promoter and 5' exon generate a novel Gs alpha mRNA.
Several species of mRNA have been shown to encode the alpha subunit of the stimulatory GTP-binding regulatory protein, Gs alpha. The various Gs alpha mRNAs are generated through alternative splicing of a single precursor RNA and through the use of alternative acceptor splice sites. We now report the existence of a Gs alpha mRNA that uses a previously unidentified promoter and leading exon (termed exon 1'). In both the canine and human Gs alpha genes, exon 1' is located 2.5 kilobases 5' of exon 1. Exon 1' does not contribute an in-frame ATG, and thus its mRNA encodes a truncated form of Gs alpha. Initiation of translation is predicted to begin at an AUG in exon 2, as demonstrated both by in vitro translation and COS cell expression studies.


Semiparametric estimation exploiting covariate independence in two-phase randomized trials.
Recent results for case-control sampling suggest when the covariate distribution is constrained by gene-environment independence, semiparametric estimation exploiting such independence yields a great deal of efficiency gain. We consider the efficient estimation of the treatment-biomarker interaction in two-phase sampling nested within randomized clinical trials, incorporating the independence between a randomized treatment and the baseline markers. We develop a Newton-Raphson algorithm based on the profile likelihood to compute the semiparametric maximum likelihood estimate (SPMLE). Our algorithm accommodates both continuous phase-one outcomes and continuous phase-two biomarkers. The profile information matrix is computed explicitly via numerical differentiation. In certain situations where computing the SPMLE is slow, we propose a maximum estimated likelihood estimator (MELE), which is also capable of incorporating the covariate independence. This estimated likelihood approach uses a one-step empirical covariate distribution, thus is straightforward to maximize. It offers a closed-form variance estimate with limited increase in variance relative to the fully efficient SPMLE. Our results suggest exploiting the covariate independence in two-phase sampling increases the efficiency substantially, particularly for estimating treatment-biomarker interactions.


The perceived health risks of cannabis use in an Australian household survey.
Perceived risks of cannabis use have rarely been researched in Australia. This paper reports on the beliefs about the adverse effects of cannabis use on health, social well-being, driving, mental health and changes in cannabis over time. Survey of 918 Australian adults was conducted as part of a quarterly omnibus self-report survey of an established panel. Respondents believed that cannabis use can cause health and social problems, can adversely affect a person's ability to drive a car, can be addictive, and can lead to use of other illicit drugs. They were uncertain as to whether cannabis can cause schizophrenia and depression, and whether cannabis had become more potent over time. Prevention efforts should focus on educating the Australian people about the nature of cannabis-related harms.


Increased dye coupling in pancreatic islets from rats in late-term pregnancy.
Our previous studies have suggested that elevated lactogen, increased glucose-stimulated insulin secretion, and increased beta-cell coupling are associated. To determine whether this association occurs under conditions of physiologically increased lactogen, we have studied the extent of dye coupling in rat islets during the later stage of pregnancy. These animals have high plasma lactogen levels in the form of placental lactogen, increased plasma insulin, and decreased plasma glucose. The fluorescent tracer, Lucifer yellow CH, was microinjected into central cells of islets from both pregnant and virgin rats, and the extent of transfer was quantitated by determining the projected area of dye spread. Two area measurements were made for each injection, one around the entire discernible fluorescent region ("outer") and another around the distinct brighter region of cells surrounding the injected cell ("inner"). Pregnancy increased dye transfer, as determined by both measurements. The outer area of dye transfer was 9047 +/- 775 microns2 for the islets from pregnant rats and 4699 +/- 391 microns2 for the islets from virgin rats (P less than .001). Similarly, pregnancy increased the inner area of dye transfer, 1447 +/- 161 microns2 for the islets from pregnant rats and 795 +/- 80 microns2 for the islets from virgin rats (P less than .001). These results support the hypothesis that elevated lactogen, increased glucose-stimulated insulin secretion, and increased beta-cell dye coupling are associated under physiological conditions. The study indicates that enhanced beta-cell coupling is part of the structural and functional adaptation that the islets undergo during a subject's pregnancy and demonstrates that the extent of beta-cell coupling is regulated by a physiological condition.


Hsa_circ_0000585 promotes chemoresistance to cis-platin in epithelial cells of ovarian cancer by modulating autophagy.
Chemoresistance, i.e., resistance to cisplatin (DDP), has been a major obstacle to ovarian cancer treatment. It has been found that circular RNAs (circRNAs) play vital roles in the tumorigenesis various cancers by regulating autophagy, while few studies focusing on cisplatin-resistance ovarian cancer (CROC). The expressions of the circRNAs were detected by qRT-PCR. Short hairpin RNA targeting circRNA was used to explore the biological functions of the circRNA. Cell viability, autophagic flux, immunofluorescence, and xenograft tumors experiments were performed to further illustrate the underlying mechanisms. Hsa_circ_0000585 was increased in cisplatin-resistant SKOV3/DDP cells. Stably knocking down hsa_circRNA_0000585 expression in SKOV3/DDP cells was established by RNA interference. We found that downregulation of hsa_circ_0000585 significantly enhanced the sensitivity of DDP/SkOV3 cells to DDP. In vivo study, hsa_circRNA_0000585 knockdown significantly decreased tumor volume in nude mice. Under the measurements of western blot and cellular immunofluorescence, hsa_circ_0000585 knockdown significantly inhibited the expression of Beclin1 and P62, indicating the autophagic flux was inhibited. Administrations with autophagic inhibitor "Chloroquine (CQ)" and autophagy activator "QX77" further confirmed that hsa_circ_0000585 knockdown resulted in autophagy inhibition. Overall, this study provided a new insight into the role of circRNAs in the mechanism of DDP-resistance in ovarian cancer. Hsa_circRNA_0000585 may be promising therapeutic targets for the enhancement of the sensitivity of ovarian cancer cells to cisplatin-mediated chemotherapy.


Central retinal vascular occlusion associated with oral contraceptives.
A 40-year-old woman took oral contraceptives for four years. She developed a vascular glaucoma and one year later the eye was enucleated. No other apparent cause for the occlusion was present. The vascular occlusion consisted of a combined central retinal artery and vein occlusion with severe intimal hyperplasia. An intravascular granulomatous reaction is attributed to chronic vascular injury.


Fractional order PIλDμ controller design for satisfying time and frequency domain specifications simultaneously.
In order to achieve a desired control performance characterized by satisfying specifications in both frequency-domain and time-domain simultaneously, an optimal fractional order proportional integral derivative (PIλDμ) controller design strategy is proposed based on analytical calculation and Differential Evolution algorithm for a permanent magnet synchronous motor (PMSM) servo system in this paper. In this controller design, the frequency-domain specifications can guarantee the system stability with both gain margin and phase margin, and also the system robustness to loop gain variations. The time-domain specifications can ensure the desired step response performance with rapid rising curve, constrained overshoot, and proper power consuming. Compared with the PIλ controller and the traditional PID controller, PIλDμ controller can get obvious benefits from two more degrees of freedom of the fractional orders λ and μ on satisfying multiple constraints simultaneously and achieving better servo tracking performance for the PMSM servo system. PMSM speed tracking simulations and experiments are demonstrated to show the significant advantages of using the proposed optimal PIλDμ controller over the optimal fractional order PIλ controller and traditional integer order PID controller.


Characterization of gonadal soma-derived factor expression during sex change in the protogynous wrasse, Halichoeres trimaculatus.
Sex change in fishes provides a good experimental model for understanding the mechanisms and plasticity of sex determination and differentiation. The three-spot wrasse, Halichoeres trimaculatus is a protogynous hermaphrodite. During sex change from female to male, the ovary is replaced by the testis through the degeneration of oocytes and subsequent spermatogenesis. In the present study, we cloned a cDNA-encoding gonadal soma-derived factor (GSDF) from protogynous wrasse and examined its expression pattern in the sexually mature gonads and the sex-changing gonad induced experimentally by aromatase inhibition. Expression of gsdf was predominantly observed in the testis, and it was mainly localized to the supporting cells surrounding the spermatogonia. In the ovary, only slight expression of gsdf was observed in morphologically undifferentiated supporting cells in contact with oogonia. During sex change, strong expression of gsdf appeared first in the supporting cells surrounding the gonial germ cells before the onset of spermatogenesis. Thereafter, the expression of gsdf continually increased in the supporting cells surrounding the proliferating spermatogonia throughout the sex change. These results suggest that gsdf is involved in the proliferation of spermatogonia and subsequent spermatogenesis in both the testis and the gonad in the early stages of sex change.


Occlusal stability after Herbst treatment of patients with retrognathic and prognathic facial types : A pilot study.
The purpose of this study was to assess and compare occlusal changes induced by Herbst treatment and the stability of these changes in patients with retrognathic and prognathic facial types. The sample comprised 11 retrognathic (SNA ≤76°, SNB ≤72°, ML/NSL ≥36°) and 10 prognathic (SNA ≥83°, SNB ≥80°, ML/NSL ≤32°) patients with Class II molar relationships of ≥0.5 cusp widths bilaterally or ≥1.0 cusp width unilaterally. Both groups involved similar distributions of skeletal maturity before treatment. Study parameters were assessed on casts reflecting the situations before treatment (T0), after Herbst treatment (T1), after multibracket treatment immediately following Herbst treatment (T2), and after a mean of 31.1 months of retention (T3). Sagittal molar relationships improved by 0.8 cusp widths in the retrognathic and by 0.7 cusp widths in the prognathic group during active treatment (T0-T2). Insignificant changes of ≤0,2 cusp widths were seen in both groups during retention (T2-T3). Overjet decreased by 8.6 mm in the retrognathic and by 5.5 mm in the prognathic group during T0-T2, and both groups showed clinically irrelevant amounts of relapse by 0.7 mm during T2-T3. Overbite improved by 1.2 mm in the retrognathic and by 2.5 mm in the prognathic group during T0-T2, reaching mean values of 1.0 mm or 1.4 mm by T2, which was followed by 0.2 mm or 1.1 mm of relapse during T2-T3. Treatment with a Herbst appliance seems to offer stable correction of the sagittal occlusal relationships in Class II patients with retrognathic or prognathic facial types, with the vertical changes being more pronounced in the prognathic cases.


Central retinal artery occlusion.
Central retinal artery occlusion is characterized by sudden, painless visual loss due to blockage of retinal blood flow. It has been reported in all age groups including children but is most frequent in the sixth decade. Both thrombosis and embolism have been suggested as possible mechanisms. The emergency treatment includes intravenous acetazolamide, digital ocular massage, and inhalation of 5% carbon dioxide -- 95% oxygen for ten minutes. Following emergency treatment, immediate ophthalmologic referral and consultation is required. Comprehensive medical evaluation should be initiated to exclude systemic vascular disease.


Benzylic C(sp(3))-H Functionalization for C-N and C-O Bond Formation via Visible Light Photoredox Catalysis.
A visible light mediated highly selective benzylic C-H bond functionalization for intermolecular C-N and C-O bond formation is reported. This cross-dehydrogenative coupling reaction demonstrates a straightforward protocol for incorporating the heteroaromatics to the benzylic position. Benzylic oxidation of various alkyl aryls to corresponding carbonyl compounds has also been reported.


Mechanisms of action of CHF3381 in the forebrain.
(1) Aim of this study was to gain insight into the mechanism of action of CHF3381, a novel putative antiepileptic and neuroprotective drug. (2) CHF3381 blocked NMDA currents in primary cultures of cortical neurons: maximal effect was nearly -80% of the NMDA-evoked current, with EC(50) of approximately 5 micro M. This effect was selective, reversible, use-dependent and elicited at the concentrations reached in the rodent brain after peripheral administration of therapeutic doses. (3) CHF3381 also inhibited voltage-gated Na(+) currents in an apparently voltage-dependent manner. However, this effect could be obtained only at relatively high concentrations (100 micro M). (4) Consistent with the mild effects on voltage-gated Na(+) channels, CHF3381 (100 micro M) failed to affect electrical stimulation-evoked glutamate overflow in hippocampal slices. In contrast, the anti-convulsant agent and Na(+) channel blocker lamotrigine (100 micro M) inhibited stimulation-evoked glutamate overflow by approximately 50%. (5) CHF3381 reduced kindled seizure-induced c-fos mRNA levels within the same brain regions, and to a similar level, as the selective NMDA receptor antagonist MK801, providing circumstantial evidence to the idea that CHF3381 blocks NMDA receptors in vivo. (6) The present mechanistic studies suggest that the primary mechanism of action of CHF3381 in the forebrain is blockade of NMDA receptors. On this basis, this compound may have a potential use in other diseases caused by or associated with a pathologically high level of NMDA receptor activation.


Surgeon work input and risk in primary versus revision total joint arthroplasty.
One hundred twenty stratified nonselected cases of primary and revision total joint arthroplasties performed between 1990 and 1992 in which complete financial and clinical data were available were reviewed. All cases were performed at a single university hospital. Compared with primary total joint arthroplasty, revision surgery involved significantly more operative time, greater blood loss, increased length of stay, and a much higher complication rate. The actual physician reimbursement was not significantly more than for primary procedures. Physician reimbursement constituted 18% of the total fees collected compared with 24% for the actual prosthesis cost. Surgeons performing revision surgery devote significantly more time and are at a higher liability than when performing primary total joint arthroplasty.


An electron microscopic study on macrophages and lymphocytes in lepromatous and borderline leprosy.
We describe how macrophages are activated and phagocytose mycobacteria in lepromatous leprosy. The differentiation of macrophages into epithelioid cells and into giant cells in borderline leprosy is shown. Close apposition between macrophages and lymphocytes is seen in those areas where mycobacteria disintegrate inside macrophages.


[Bronchiolo-alveolar carcinoma and lung transplantation].
Bronchiolo-alveolar carcinoma is a controversial indication for lung transplantation because of the risk of recurrence. We report three cases and propose some risk factors for recurrence. Our study concerns three patients transplanted at the Louis-Pradel Hospital between 1991 and 2010. The first patient relapsed 86 months after transplantation, benefited from surgical treatment, then died of renal failure. A second patient died of infection, without recurrence, 72 months after transplantation. The third had an early recurrence at 7 months and died 27 months after transplantation. The risk factors for recurrence appear to be: clinically "aggressive" presentation and histological stromal pulmonary invasion by the carcinoma. Diffuse bronchiolo-alveolar carcinoma is a possible indication of lung transplantation. The risk of recurrence imposes some requirements: a precise histological diagnosis and a slow clinical course.


Differences of Recovery from Rocuronium-induced Deep Paralysis in Response to Small Doses of Sugammadex between Elderly and Nonelderly Patients.
WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Complete recovery from rocuronium-induced muscle paralysis with sugammadex is reported to be delayed in elderly patients. The authors tested a hypothesis that recovery from deep neuromuscular block with low-dose sugammadex is slower (primary hypothesis) and incidence of recurarization is higher (secondary hypothesis) in elderly patients than in nonelderly patients. In anesthetized elderly (n = 20; 76.9 ± 5.0 yr of age) and nonelderly patients (n = 20; 53.7 ± 12.8 yr of age) under deep paralysis with rocuronium, change of train-of-four ratio per minute (primary outcome variable) was measured with an acceleromyograph neuromuscular monitor during spontaneous recovery from rocuronium-induced muscle paralysis (0.6 mg/kg) and after infusion of low-dose sugammadex (50 µg · kg · min). Recurarization was defined as the negative change of train-of-four ratio. Spontaneous train-of-four ratio recovery rate was significantly slower in the elderly group (median [25th percentile, 75th percentile]: 1.89 [1.22, 2.90] %/min) than in the nonelderly group (3.45 [1.96, 4.25] %/min, P = 0.024). Train-of-four ratio change rate in response to low-dose sugammadex was significantly slower in elderly (0.55 [-0.29, 1.54] %/min) than in the nonelderly group (1.68 [0.73, 3.13] %/min, P = 0.024). Incidence of recurarization was significantly higher in the elderly group than in the nonelderly group (35% vs. 5%, P = 0.044). Multiple linear regression analyses indicate that slower spontaneous train-of-four ratio recovery rate and impaired renal function are two major contributing factors that decrease train-of-four ratio change rate in response to low-dose sugammadex. Elderly patients are at greater risk for recurarization and residual muscle paralysis when low-dose sugammadex is administered.


In silico analysis of noscapine compounds as anti-tumor agents targeting the tubulin receptor.
This research aims to develop a mathematical model that relates the structural features of noscapine with anti-tumor activity, to explains the mode of binding between noscapine compounds and the target receptor tubulin by docking analysis. By considering the results of docking analysis and predictions of pharmacokinetic properties/drug likeness, we designed novel noscapine compounds as anti-tumor agents against pancreatic cancer. We used an in silico quantitative structure-activity relationship (QSAR) approach, molecular docking analysis and online tools for pharmacokinetics and drug likeness prediction to develop novel compounds. A QSAR model with good validations parameters and quality of fit (R2 = 0.9731, Q2 CV = 0.9434, R2 adj = 0.9647 and R2 test set = 0.8343) was built utilizing 70% of the dataset as a training set and the remaining 30% as an external validation to ascertain its predictive capability. Three novel compounds were designed: D3, D4 and D6 with binding scores of -11.2, -10.2 and 10.6 kcal/mol, respectively, exhibiting high affinity towards the tubulin receptor than the template (parent compound) and the co-crystallized ligand (E∗) with a binding score of 9.2 kcal/mol. The QSAR approach and molecular docking analysis is an important approach for modern drug discovery. Pharmacokinetics studies of the selected novel compounds revealed good drug properties and can be used as candidate compounds for the development of anti-tumor agents for pancreatic cancer.


IsoPSA® Reduces Provider Recommendations for Biopsy and Magnetic Resonance Imaging in Men with Total Prostate Specific Antigen ≥4 ng/ml: A Real-World Observational Clinical Utility Study.
We assessed the impact of the IsoPSA® test for prostate cancer risk assessment on provider patient management decisions in a real-world clinical setting. A total of 38 providers, including advanced practice providers, fellowship trained oncologists and general urologists in the Cleveland Clinic health system including both community-based practices and academic locations, enrolled 900 men being evaluated for prostate cancer; 734 met inclusion criteria (age ≥50 years, total serum prostate specific antigen [PSA] ≥4 and <100 ng/ml and no history of prostate cancer) and IsoPSA indication for use. A standard template was used to document biopsy recommendation prior to and after receiving IsoPSA results. The primary outcome was the number of biopsy and magnetic resonance imaging recommendation changes occurring after IsoPSA testing. IsoPSA testing resulted in a 55% (284 vs 638) net reduction in recommendations for prostate biopsy for men with total PSA ≥4 ng/ml. Additionally, a 9% reduction in recommendations for magnetic resonance imaging was observed. There was strong concordance between IsoPSA results and provider recommendations for prostate biopsy, with 87% of patients with an IsoPSA index above the threshold recommended for biopsy and 92% of patients with an IsoPSA index below the threshold not recommended for biopsy. In a real-world clinical setting, providers from diverse training backgrounds and practice settings readily adopted IsoPSA with substantial reductions in the rate of recommended prostate biopsies in patients with elevated PSA values (≥4 ng/ml). There was a high concordance between recommendation for or against prostate biopsy and the IsoPSA result.


A highly efficient synthesis of telaprevir by strategic use of biocatalysis and multicomponent reactions.
A very short and efficient synthesis of the important drug candidate telaprevir, featuring a biocatalytic desymmetrization and two multicomponent reactions as the key steps, is presented. The classical issue of lack of stereoselectivity in Ugi- and Passerini-type reactions is circumvented. The atom economic and convergent nature of the synthetic strategy require only very limited use of protective groups.


An automated method to measure monoamines and metabolites using elevated temperature reversed phase HPLC with electrochemical detection. Application to striatal dopamine and hippocampal serotonin turnover.
High pressure liquid chromatography with electrochemical detection has been successfully used for the analysis of noradrenaline, dopamine(DA), serotonin(5-HT), and selected metabolites in brain. Automated sample injection allows up to 100 samples per day to be analyzed; precise thermostatic control of the chromatography at 45 degrees C increases both method reproducibility and separation efficiency while increasing column life. The method requires minimal sample pretreatment and is rapid and inexpensive. It has been applied to the analysis of rat and mouse whole brain and, in particular, to milligram samples of rat striatum and hippocampus, thus permitting the measurement of regional DA and 5-HT turnover. Effects of selected psychotropic drugs on these processes illustrate the value of the method to either DA or 5-HT turnover studies.


The effect of calcium channels blockers in the K+-evoked release of [3H]adenine nucleotides from rat brain cortical synaptosomes.
The role of L-,N-, P- and Q-type voltage-dependent calcium channels in K+-induced release of [3H]adenine nucleotides from rat brain cortical synaptosomes was investigated. Cd2+, a non-specific blocker of calcium channels, inhibited by 69% the release of the nucleotides induced by 33 mM K+. Nifedipine, omega-Conotoxin GVIA and omega-Agatoxin IVA had no effect whereas omega-Conotoxin MVIIC inhibited by 62% the K+ induced release of adenine nucleotides in rat brain cortical synaptosomes. It is concluded that Q-type calcium channels are directly involved in the release of adenine nucleotides in rat brain cortical synaptosomes.


Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid (TDGA) on glucose and fatty acid oxidation in isolated rat soleus muscle.
1. The effect of 2-tetradecylglycidic acid (TDGA), a potent, specific inhibitor of long-chain fatty acid oxidation, on fatty acid and glucose oxidation by isolated rat soleus muscle was studied. 2. TDGA inhibited [1-14C]palmitate oxidation by soleus muscle in a concentration-dependent manner. 3. TDGA inhibited the activity of soleus muscle mitochondrial carnitine palmitoyltransferase A (CPT-A). 4. Added palmitate (0.5 mM) significantly inhibited D-[U-14C]glucose oxidation and, under conditions where TDGA inhibited palmitate oxidation, the oxidation of D-[U-14C]glucose by isolated soleus muscle was significantly stimulated. 5. TDGA stimulation of glucose oxidation was reversed by octanoate, a medium-chain fatty acid whose oxidation is not inhibited by TDGA. 6. When nondiabetic rats were treated with TDGA (10 mg/kg p.o./day x 3 days), fasting plasma glucose was significantly lowered and the ability of isolated contralateral soleus muscles to oxidize palmitate was inhibited while glucose oxidation was significantly stimulated.


A multisource mass transfer model for simulating VOC emissions from paints.
Indoor decoration generates a large number of volatile organic compounds (VOCs), which are simultaneously released from different paints. Nevertheless, the interaction mechanism of pollutant diffusion from multisource building materials (such as primer and finish) needs to be examined. In this paper, a multisource mass transfer model for VOC emissions from different combinations of paints is established, and the analytical solution is derived. The finite difference method is used to simulate the experimental results of VOC release in the environmental chambers, and its convergence and stability are verified. Using the optimization parameters of the single-source model and the law of conservation of mass, the key parameters of the multisource mass transfer model are obtained. The results show that the established model is in excellent agreement with both experimental data and literature data. In addition, the Little number Lt is used to analyse the change trend from the initial released concentration in the single-source and multisource models.


[So-called ocular hypertension and new signs of primary open-angle glaucoma].
Between normal and glaucomatous subjects, a group with ocular hypertension exists which is not homogeneous as 10 p. cent of these will develop glaucoma. The problem is to select early eyes at risk. Three new methods of examination have been proposed: the response to the test of contrast sensitivity, the pupillary reaction test of Marcus Gunn, and photographic exploration of the nerve fiber layer of the retina.


Screening, prevention, and ambitious management of diabetic macular edema in patients with type 1 diabetes.
Diabetic macular edema results from progressive retinopathy related to chronic hyperglycemic and inflammatory vascular damage. Loss of vision secondary to diabetic macular edema is the most common cause of vision loss in patients with diabetes. Blood glucose control remains the main means of preventing progression of retinopathy and macular edema. Recent advancements allowing more efficient mechanisms for screening patients and emerging treatments for macular edema have led to improved visual outcomes in this group of patients.


Partial Pressure of Arterial Oxygen in Healthy Adults at High Altitudes: A Systematic Review and Meta-Analysis.
With increasing altitude, the partial pressure of inspired oxygen decreases and, consequently, the Pao2 decreases. Even though this phenomenon is well known, the extent of the reduction as a function of altitude remains unknown. To calculate an effect size estimate for the decrease in Pao2 with each kilometer of vertical gain among healthy unacclimatized adults and to identify factors associated with Pao2 at high altitude (HA). A systematic search of PubMed and Embase was performed from database inception to April 11, 2023. Search terms included arterial blood gases and altitude. A total of 53 peer-reviewed prospective studies in healthy adults providing results of arterial blood gas analysis at low altitude (<1500 m) and within the first 3 days at the target altitude (≥1500 m) were analyzed. Primary and secondary outcomes as well as study characteristics were extracted from the included studies, and individual participant data (IPD) were requested. Estimates were pooled using a random-effects DerSimonian-Laird model for the meta-analysis. Mean effect size estimates and 95% CIs for reduction in Pao2 at HA and factors associated with Pao2 at HA in healthy adults. All of the 53 studies involving 777 adults (mean [SD] age, 36.2 [10.5] years; 510 men [65.6%]) reporting 115 group ascents to altitudes between 1524 m and 8730 m were included in the aggregated data analysis; 13 of those studies involving 305 individuals (mean [SD] age, 39.8 [13.6] years; 185 men [60.7%]) reporting 29 ascents were included in the IPD analysis. The estimated effect size of Pao2 was -1.60 kPa (95% CI, -1.73 to -1.47 kPa) for each 1000 m of altitude gain (τ2 = 0.14; I2 = 86%). The Pao2 estimation model based on IPD data revealed that target altitude (-1.53 kPa per 1000 m; 95% CI, -1.63 to -1.42 kPa per 1000 m), age (-0.01 kPa per year; 95% CI, -0.02 to -0.003 kPa per year), and time spent at an altitude of 1500 m or higher (0.16 kPa per day; 95% CI, 0.11-0.21 kPa per day) were significantly associated with Pao2. In this systematic review and meta-analysis, the mean decrease in Pao2 was 1.60 kPa per 1000 m of vertical ascent. This effect size estimate may improve the understanding of physiological mechanisms, assist in the clinical interpretation of acute altitude illness in healthy individuals, and serve as a reference for physicians counseling patients with cardiorespiratory disease who are traveling to HA regions.


Alkaline and ultrasound assisted alkaline pretreatment for intensification of delignification process from sustainable raw-material.
Alkaline and ultrasound-assisted alkaline pretreatment under mild operating conditions have been investigated for intensification of delignification. The effect of NaOH concentration, biomass loading, temperature, ultrasonic power and duty cycle on the delignification has been studied. Most favorable conditions for only alkaline pretreatment were alkali concentration of 1.75 N, solid loading of 0.8% (w/v), temperature of 353 K and pretreatment time of 6 h and under these conditions, 40.2% delignification was obtained. In case of ultrasound-assisted alkaline approach, most favorable conditions obtained were alkali concentration of 1N, paper loading of 0.5% (w/v), sonication power of 100 W, duty cycle of 80% and pretreatment time of 70 min and the delignification obtained in ultrasound-assisted alkaline approach under these conditions was 80%. The material samples were characterized by FTIR, SEM, XRD and TGA technique. The lignin was recovered from solution by precipitation method and was characterized by FTIR, GPC and TGA technique.


Developing specialist healthcare for older people: a challenge for the European Union.
The state of health in the European Union is better than ever before. This is due to spectacular progress made over the second half of this century in terms of medical research, health services provision and living conditions. However, older people require more, and substantially different, health and care services than younger people. The central challenge of the policy makers is to ensure that future health care policies will provide an adequate and cost effective response to the changes brought about by demographic trends.


Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis.
Antibodies to aquaporin-4 (AQP4-Ab) are found in 60-80% of patients with neuromyelitis optica (NMO), a severely disabling inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the optic nerves and spinal cord. To assess the frequency of AQP4-Ab in patients with optic neuritis (ON), and to investigate the prognostic implications of AQP4-Ab seropositivity in such patients. AQP4-Ab serum levels were determined in 224 individuals from Austria, Denmark, France, Germany, Italy, and Turkey using a newly developed fluorescence immunoprecipitation assay employing recombinant human AQP4. AQP4-Ab were detectable in 8/139 (5.8%) patients with acute monosymptomatic optic neuritis (AMON) and in 10/17 (58.8%) patients with established NMO and a last relapse of acute ON (NMO/ON), but not in 32 patients with multiple sclerosis or in 36 healthy controls. At last examination, 4/8 (50%) seropositive AMON patients had met the criteria for NMO but 0/128 seronegative AMON patients. Disease severity differed significantly between seropositive and seronegative AMON. Complete bilateral or unilateral blindness occurred in six AQP4-Ab positive patients, but only in one AQP4-Ab negative patient. AQP4-Ab levels did not vary between seropositive AMON and NMO/ON and did not correlate with disease severity. Female gender, a relapsing course, and concomitant autoimmunity were associated with AQP4-Ab seropositive status and risk of developing NMO. AQP4-Ab is relatively rare among patients with AMON, but if present it predicts a high rate of conversion to NMO within one year.


Decision making: Dopaminergic neurons for better or worse.
All animals constantly need to weigh their options based on new experiences: something initially considered bad can become better in the light of something worse. A new study now shows how flies re-evaluate between better and worse.


Incorporating pharmacodynamic considerations into caffeine therapeutic drug monitoring in preterm neonates.
This study sought to assess the pharmacokinetic and pharmacodynamic relationships of caffeine citrate therapy in preterm neonates who had therapeutic drug monitoring (TDM) in the post-extubation period. A retrospective observational study was conducted in preterm neonates who received caffeine citrate therapy for apnea of prematurity and had TDM done in the post-extubation period between January 2006 and October 2011. The relationships between pharmacodynamic effects (heart rate, respiratory rate, episodes of apnea, adverse events) and caffeine serum concentrations were explored. A total of 177 blood samples were obtained from 115 preterm neonates with a median (range) gestational age of 29 (24 - 33) weeks and birth weight of 1230 (607 - 2304) kg. Caffeine citrate therapy was initiated at a median (interquartile range) postnatal age of 1 (1 - 3) day and TDM was performed at a postnatal age of 15 (10 - 24) days. No direct correlations were found between respiratory rate or apneic episodes and caffeine serum concentrations; however, heart rate and caffeine serum concentrations were significantly correlated (p < 0.05). Dosing regimen of 40/5 mg/kg q12h (loading dose/maintenance dose, time interval) led to similar endotracheal re-intubation rate but increased percentage of patients experiencing tachycardia compared to the standard regimen of 20/5 mg/kg q24h (44.7 % vs 10.2 %, p < 0.001). Based on this retrospective study, no correlation between episodes of apnea and caffeine serum concentrations was found in neonates who had TDM of caffeine citrate therapy in the post-extubation period, whereas a significant association between tachycardia and concentrations existed. Notwithstanding the absence of severe adverse reactions, TDM should be considered in critically ill neonates with unexplained adverse effects, such as tachycardia.


Reconsidering phosphorylation in the control of inducible CARD11 scaffold activity during antigen receptor signaling.
Protein phosphorylation is a commonly used regulatory step that controls signal transduction pathways in a wide array of biological contexts. The finding that a residue is phosphorylated, coupled with the observation that mutation of that residue impacts signaling, often forms the basis for concluding that the phosphorylation of that residue is a key signaling step. However, in certain cases, the situation is more complicated and warrants further study to obtain a clear mechanistic understanding of whether and how the kinase-mediated modification in question is important. CARD11 is a multi-domain signaling scaffold that functions as a hub in lymphocytes to transmit the engagement of antigen receptors into the activation of NF-κB, JNK and mTOR. The phosphorylation of the CARD11 autoinhibitory Inhibitory Domain in response to antigen receptor triggering has been proposed to control the signal-induced conversion of CARD11 from an inactive to an active scaffold in a step required for lymphocyte activation. In this review, I discuss recent data that suggests that this model should be reconsidered for certain phosphorylation events in CARD11 and propose possible experimental avenues for resolution of raised issues.


Quaternary ammonium bromide functionalized polyethylene glycol: a highly efficient and recyclable catalyst for selective synthesis of 5-aryl-2-oxazolidinones from carbon dioxide and aziridines under solvent-free conditions.
A quaternary ammonium bromide covalently bound to polyethylene glycol (PEG, MW = 6000), i.e., PEG(6000-)(NBu(3)Br)2, was found to be an efficient and recyclable catalyst for the cycloaddition reaction of aziridines to CO(2) under mild conditions without utilization of additional organic solvents or cocatalysts. As a result, 5-aryl-2-oxazolidinone was obtained in high yield with excellent regioselectivity. The catalyst worked well for a wide variety of 1-alkyl-2-arylaziridines. Besides, the catalyst could be recovered by centrifugation and reused without significant loss of catalytic activity and selectivity.


Sex differences in obstructive sleep apnoea.
Obstructive sleep apnoea (OSA) and obstructive sleep apnoea/hypopnoea syndrome (OSAHS) have long been considered predominantly male-related conditions. The clinical presentation of sleep disordered breathing in females differs from males and can vary with age and physiological status, e.g. menopause and pregnancy. Overall, females appear to be more symptomatic, with lower apnoea-hypopnoea index scores compared to males. Furthermore, they appear to have more prolonged partial upper airway obstruction, and may report insomnia as a symptom of OSAHS more frequently. As a consequence of these differences in clinical presentation, females with sleep disordered breathing are often underdiagnosed and undertreated compared to males. This review is aimed at discussing the epidemiology, clinical presentation, pathophysiology and hormonal and metabolic differences in females who present with OSA/OSAHS in comparison to males.


Adsorption properties and structure of CO2 adsorbed on open coordination sites of metal-organic framework Ni2(dhtp) from gas adsorption, IR spectroscopy and X-ray diffraction.
The microporous metal-organic framework Ni(2)(dhtp) (H(4)dhtp=2,5-dihydroxyterephthalic acid) shows distinct end-on CO(2) coordination to coordinatively unsaturated nickel sites giving rise to high CO(2) adsorption capacity at sub-atmospheric pressures and ambient temperatures.


Personal Health Data Tracking by Blind and Low-Vision People: Survey Study.
Personal health technologies, including wearable tracking devices and mobile apps, have great potential to equip the general population with the ability to monitor and manage their health. However, being designed for sighted people, much of their functionality is largely inaccessible to the blind and low-vision (BLV) population, threatening the equitable access to personal health data (PHD) and health care services. This study aims to understand why and how BLV people collect and use their PHD and the obstacles they face in doing so. Such knowledge can inform accessibility researchers and technology companies of the unique self-tracking needs and accessibility challenges that BLV people experience. We conducted a web-based and phone survey with 156 BLV people. We reported on quantitative and qualitative findings regarding their PHD tracking practices, needs, accessibility barriers, and work-arounds. BLV respondents had strong desires and needs to track PHD, and many of them were already tracking their data despite many hurdles. Popular tracking items (ie, exercise, weight, sleep, and food) and the reasons for tracking were similar to those of sighted people. BLV people, however, face many accessibility challenges throughout all phases of self-tracking, from identifying tracking tools to reviewing data. The main barriers our respondents experienced included suboptimal tracking experiences and insufficient benefits against the extended burden for BLV people. We reported the findings that contribute to an in-depth understanding of BLV people's motivations for PHD tracking, tracking practices, challenges, and work-arounds. Our findings suggest that various accessibility challenges hinder BLV individuals from effectively gaining the benefits of self-tracking technologies. On the basis of the findings, we discussed design opportunities and research areas to focus on making PHD tracking technologies accessible for all, including BLV people.


[Lymphography with lymph node puncture biopsy. A reliable procedure for assessing the lymphatic spread of bladder tumors].
119 patients with bladder tumors of category Ta, Tis, T4, considered for radical treatment because of local conditions were studied by pedal lymphography (LAG) and percutaneous fine needle aspiration biopsy (FNA). 41% had a positive LAG. Adequate material was obtained for FNA in 94% of the patients. Of 70 patients with normal LAG none had a positive FNA; only 36% of those with a positive LAG had a positive FN. The high rate of positive LAG with negative FNA is attributed to inflammatory changes due to previous transurethral resection. Radical lymphadenectomy (LND) was done in 64 patients of whom 54 had a negative FNA. In this group, 8 (17%) had a positive LND. There was no mortality and morbidity was mild. LAG with FNA has a role in the pre-operative staging of bladder carcinoma.


Genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food.
Here, we conducted in vitro genotoxicity tests to evaluate the genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food. Styrene oligomers were extracted with acetone and the extract was subjected to the Ames test (OECD test guideline No. 471) and the in vitro chromosomal aberration test (OECD test guideline No. 473) under good laboratory practice conditions. The concentrations of styrene dimers and trimers in the concentrated extract were 540 and 13,431 ppm, respectively. Extraction with acetone provided markedly higher concentrations of styrene oligomers compared with extraction with 50% ethanol aqueous solution, which is the food simulant currently recommended for use in safety assessments of polystyrene by both the United States Food and Drug Administration and the European Food Safety Authority. And these high concentrations of styrene dimers and trimers were utilized for the evaluation of genotoxicity in vitro. Ames tests using five bacterial tester strains were negative both in the presence or absence of metabolic activation. The in vitro chromosomal aberration test using Chinese hamster lung cells (CHL/IU) was also negative. Together, these results suggest that the risk of the genotoxicity of styrene oligomers that migrate from polystyrene food packaging into food is very low.


Combination versus successive single agent chemotherapy in lymphocytic lymphoma.
Fifty-three patients with advanced lymphocytic lymphoma were randomly assigned to treatment with the combination cyclophosphamide, vincristine, and prednisone (CVP) or the same agents used successively in maximal doses (C-V-P). Complete remissions occurred in 68% with CVP and 48% with C-V-P. For patients with nodular lymphoma, the complete remission rate was 81% with CVP and 46% with C-V-P. In patients with diffuse lymphoma a complete remission rate of 50% was obtained with both regimens. The median duration of response was longer for patients who obtained complete remission with CVP (37+ months) than for those entering remission with C-V-P (25+ months). More patients treated with CVP still survive. Current results suggest that CVP is a better induction regime than C-V-P in patients with nodular lymphoma. However, in patients with diffuse lympoocytic lymphoma, neither regimen results in more than 50% complete remissions or significant numbers of prolonged responses. More effective therapy is needed.


From achiral porphyrins to template-imprinted chiral aggregates and further. Self-replication of chiral memory from scratch.
The presence of 10-13 M of chiral clusters of aromatic amino acids addresses aggregation of opposite-charged achiral porphyrin towards the formation of smart chiral assemblies. The latter supramolecular complexes are able to self-propagate and transfer their chiral information with a 100% yield. The chiral bias occurs through a correlated sequence of induction, memory, and amplification of chirality that strongly recalls possible prebiotic scenarios.


Atherosclerosis of the carotid arteries in young patients with familial hypercholesterolemia.
Patients with heterozygous and homozygous Familial Hypercholesterolemia exhibit a high incidence of premature coronary heart disease, presumably due to atheromatous plaque-formation in the coronary arteries. Clinical symptoms develop when the disease has progressed to more severe stages of atherosclerosis. Aim of our study was to visualize and document early atheromatous lesions in the carotid arteries of asymptomatic patients with familial hypercholesterolemia under 30 years of age by Duplex-scan. Of 44 patients, 70% had detectable carotid plaques, while only 12% of the controls were affected. All patients with severe carotid disease had serum cholesterol levels above 350 mg/dl. In the age group 2-20 years, 66% of the patients exhibited plaques. Only 6% of the FH patients 21-30 years had normal carotid arteries. We conclude that the process of atheromatous plaque formation in patients with FH starts early in life, severity of atherosclerosis being a function of both extent and duration of hypercholesterolemia. Duplex-scan examination of the carotid arteries is efficient and precise non-invasive method suitable to visualize this process and, by measuring regression, monitor the efficacy of therapeutic measures.


Global metabolome analysis of Dunaliella tertiolecta, Phaeobacter italicus R11 Co-cultures using thermal desorption - Comprehensive two-dimensional gas chromatography - Time-of-flight mass spectrometry (TD-GC×GC-TOFMS).
Dunaliella tertiolecta is a marine microalgae that has been studied extensively as a potential carbon-neutral biofuel source (Tang et al., 2011). Microalgae oil contains high quantities of energy-rich fatty acids and lipids, but is not yet commercially viable as an alternative fuel. Carefully optimised growth conditions, and more recently, algal-bacterial co-cultures have been explored as a way of improving the yield of D. tertiolecta microalgae oils. The relationship between the host microalgae and bacterial co-cultures is currently poorly understood. Here, a complete workflow is proposed to analyse the global metabolomic profile of co-cultured D. tertiolectra and Phaeobacter italicus R11, which will enable researchers to explore the chemical nature of this relationship in more detail. To the best of the authors' knowledge this study is one of the first of its kind, in which a pipeline for an entirely untargeted analysis of the algal metabolome is proposed using a practical sample preparation, introduction, and data analysis routine.


LncRNA and mRNA expression profiles and functional networks of hyposalivation of the submandibular gland in hypertension.
Hyposalivation is a complication of hypertension. However, little is known about the role of long non-coding RNAs (lncRNAs) in salivary glands in hypertension. This study aimed to compare the lncRNA and mRNA expression profiles between spontaneous hypertension rats (SHRs) and Wistar-Kyoto (WKY) rats through microarray analysis and apple bioinformatics methods to analyse their potential roles in hyposalivation. The differentially expressed (DE) lncRNAs and mRNAs were confirmed by quantitative real-time PCR (qRT-PCR). Compared with WKY rats, 225 DE lncRNAs and 473 DE mRNAs were identified in the SMG of SHRs. The pathway analyses of DE mRNAs showed that inflammatory mediator regulation of transient receptor potential channels was involved in hyposalivation in SHRs. Ten DE lncRNAs were chosen for further research. A coding-non-coding gene co-expression (CNC) network and competing endogenous RNA (ceRNA) network analysis revealed that the potential functions of these 10 DE lncRNAs were closely connected with the processes of the immune response. This study showed abundant DE lncRNAs and mRNAs in hypertensive SMGs. Furthermore, our results indicated strong associations between the immune response and hyposalivation and showed the potential of immune-related genes as novel and therapeutic targets for hyposalivation.


Assessment of soft tissue lesions suspicious for liposarcoma by F18-deoxyglucose (FDG) positron emission tomography (PET).
F18-deoxyglucose (FDG) positron emission tomography (PET) is a promising imaging technique. The aim of this study was to investigate the use of FDG PET in patients with suspected liposarcomas (LS). Forty-two masses were studied. The FDG uptake was estimated in tumor (T) and normal tissue (NT). The data were analyzed with respect to pathological findings. Pathology revealed 11 primary LS, 14 locally recurrent LS, 5 other sarcomas, 1 inflammation, 1 lymphoma and 10 benign lesions. FDG uptake (T-to-NT ratio) in 25 LS corresponded with the histological subtype. Pleomorphic, mixed and myxoid LS showed an increased T-to-NT ratio and were thus visualized. Four out of six well-differentiated LS presented a low FDG uptake. Like subtype, the tumor grade also corresponded to FDG uptake. The T-to-NT ratio of higher grade LS, contrary to low grade LS, was uniformly increased. Primary LS were distinguishable from benign tumors, while other sarcomas, inflammation and lymphoma were not. Recurrence was detected with a sensitivity of 86% and a specificity of 100%. False-negative diagnoses occurred only in well-differentiated recurrences. FDG uptake in LS correlates with the histological subtype and tumor grade. The diagnostic value of FDG PET in LS, therefore, is influenced by histomorphological parameters. Our data suggest that pleomorphic, mixed and higher-grade LS recurrences are preferentially amenable to FDG PET imaging.


Enhancing anti-melanoma outcomes in mice using novel chitooligosaccharide nanoparticles loaded with therapeutic survivin-targeted siRNA.
Melanoma anti-tumor therapy remains a challenge. SiRNA-based therapies provide a powerful means, but limitations remain in its pharmaceutical applications owing to the lack of highly efficient delivery systems. In this study, to improve the siRNA delivery efficiency of chitooligosaccharide (COS), phenylboronic acid (PBA)-modified COS was synthesized and structurally characterized. PBA-modified COS was used to deliver survivin-targeted siRNA for melanoma treatment. The siRNA-loaded nanoparticles were prepared by a synergetic assembly of electrostatic complexation and chemical cross-linking. The particle size and zeta potential were characterized by dynamic light scattering, and transmission electron microscopy was utilized to observe the morphology of the nanoparticles. The cellular uptake of nanoparticles on B16F10 cells was studied by flow cytometry and confocal laser scanning microscopy. A luciferase reporter gene assay determined the gene silencing efficiency of different nanoparticles. As a result, the novel nanoparticles remarkably inhibited the proliferation of B16F10 cells in vitro and significantly inhibited the growth and metastasis of melanoma in vivo. In conclusion, PBA-modified COS can serve as a promising carrier for siRNA delivery in the field of anti-tumor therapy.


Relationship between growth temperature and shedding of lipopolysaccharides by gram-negative bacilli.
To explore the possibility that physiologically elevated temperatures might reduce the shedding of lipopolysaccharides (LPS) by gram-negative bacteria, the in vitro rates of growth and LPS release by Escherichia coli 055 and Salmonella typhimurium were compared at 33 degrees C, 37 degrees C and 41 degrees C. Rates of LPS accumulation in liquid culture supernatants were measured by radioimmunoassay for O-antigen. Escherichia coli 055 cells, adapted to 35 degrees C and then grown at different temperatures, showed increased growth and LPS release rates parallel with rising incubation temperatures. The growth of a clinical isolate of Salmonella typhimurium (not a laboratory strain) was suppressed slightly at 33 degrees C, but LPS shedding was unaffected by temperature changes. Adaptation of Escherichia coli 055 to 40 degrees C was associated with a smooth-rough transition and a reduced release rate of O-antigen, but no difference in growth rate when compared with a 35 degrees C-adapted strain. Thus, the release rate of LPS by gram-negative bacteria does not necessarily parallel their growth rate. This mechanism does not seem to explain the apparently beneficial effect of fever on the outcome of gram-negative infections in higher animals.


Transmission of Work Ethic in African-American Families and Its Links with Adolescent Adjustment.
A strong work ethic generally has positive implications for achievements in work and school settings, but we know little about how it develops. This study aimed to describe the intra-familial transmission of work ethic and the associations between work ethic and adjustment in African American youth. Mothers, fathers, and two adolescent siblings (M age = 14.1 years) in 158 families were interviewed on two occasions. Path models revealed that fathers' work ethic was positively linked with older siblings' work ethic, which in turn was linked with more positive youth adjustment in the domains of school functioning and externalizing and internalizing problems. Moreover, the results indicated that the work ethics of older siblings, but not parents, was linked to those of younger siblings. The discussion focuses on the importance of African American fathers and siblings in youth adjustment and how work ethic may promote positive development.


High serum levels of transforming growth factor β1 are associated with increased cortical thickness in cingulate and right frontal areas in healthy subjects.
Transforming growth factor β (TGF-β) is a cytokine having multiple functions in the central nervous system such as promoting repair mechanisms in degenerative diseases and stroke. To date, however, its neuroprotective effects in non-disease conditions have not been studied With the aim of exploring the relationship between peripheral TGF-β1 expression and brain structural integrity, 70 healthy participants underwent high-resolution structural T1-weighted magnetic resonance imaging scans and blood sampling. Data were processed to obtain brain cortical thickness and serum concentrations of TGF-β1. We investigated the correlation between TGF-β1 and cortical thickness using both region-of-interest- and vertex-based approaches. Region-of-interest-based analysis of the cortical mantle showed a correlation between TGF-β1 serum concentrations and cortical thickness bilaterally in cingulate and right frontal and temporal areas. Similar results emerged in the vertex-based analysis, where significant correlations were found bilaterally in cingulate and right frontal cortices. These results suggest that TGF-β1, through its role in down-regulating inflammatory processes, might have a beneficial effect on the structural integrity of the brain in physiological states.


Oral myiasis: A known case of scar epilepsy in a 45-year-old.
Oral myiasis (OM) is brought on by parasitic larvae that consume both living and dead tissue. Our study aims to present the possible circumstances under which people suffer from this deteriorating condition in juxtaposition to scar epilepsy. A uncommon disease known as oral myiasis (OM) is brought on by parasitic larvae that consume both living and dead tissue. OM cases in humans are scarce, although most of those reported come from developing nations or tropical regions. This case report describes a rare larvae infestation in the oral cavity of a 45-year-old woman who had previously undergone a ventriculoperitoneal (VP) shunt procedure, convulsions, and fever. The patient presented with episodic grand-mal seizures accompanied by fever for 2 days. She is a known case of scar epilepsy and underwent VP shunting due to hydrocephalus post-meningoencephalitis 16 years ago. The patient subsequently underwent symptomatic treatment and was later diagnosed with OM during her management. Histopathology of the biopsy following wound debridement revealed invasive fungal growth causing necrosis and erosion of the buccal mucosa and palate with no evidence of malignancy. The presentation of OM is an infrequent and exclusively rare entity. Our study aims to present the possible circumstances under which people suffer from this deteriorating condition in juxtaposition to scar epilepsy. This case report highlights the significance of prompt medicinal intervention and debridement coupled with preventative measures undertaken for a better prognosis and longevity.