Mucus Plugs and Small Airway Dysfunction in Asthma, COPD, and Asthma-COPD Overlap.
There are reports concerning mucus plugs detected on high-resolution computed tomography images and airflow obstruction in asthma and chronic obstructive pulmonary disease (COPD). However, little is known about the associations between mucus plugs and small airway dysfunction (SAD). We evaluated the relationship between mucus plugs and pulmonary function in patients with asthma, COPD, and asthma-COPD overlap (ACO), and investigated the relevance to SAD and type 2 inflammation in a retrospective study. Subjects included 49 asthmatic, 40 ACO, and 41 COPD patients. ACO was diagnosed based on the Japanese Respiratory Society ACO guidelines. Clinical and laboratory parameters, including blood eosinophil count, serum total IgE levels, fractional exhaled nitric oxide (FeNO), spirometry, and forced oscillation technique (FOT), were compared between patients with and without mucus plugs. Mucus plugs were found in 29 (59%) asthmatic, 25 (65%) ACO, 17 (41%) COPD patients. Patients with mucus plugs had reduced spirometry and larger FOT parameters, especially in COPD patients. Mucus scores correlated positively with IgE in ACO and FeNO in asthmatic patients, but not in COPD patients. Multivariate logistic regression analysis revealed that SAD parameters, including forced vital capacity and resonant frequency, a respiratory reactance parameter, were significantly associated with the presence of mucus plugs in the whole studied population. SAD, rather than large airway dysfunction, was associated with mucus plugs in asthma, ACO, and COPD patients.


High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model.
Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D₃ has been considered a viable adjunctive therapy in IBD. However, vitamin D₃ plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D₃ supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10-/- CD4⁺ T cell transfer model of chronic colitis. High-dose vitamin D₃ supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D₃ metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D₃ supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D₃ diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D₃ group. Our data suggest that vitamin D₃, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D₃ supplementation in patients with active IBD.


Domiciliation trend of Panstrongylus rufotuberculatus in Colombia.
The present paper presents evidence of the domiciliation of Panstrongylus rufotuberculatus in La Gardenia, Colombia through the collection of 2 unhatched eggs, 81 nymphs and 10 adults (4 males and 6 females), from 2 rural houses. The transmission risk indicators of Trypanosoma cruzi by P. rufotuberculatus in La Gardenia, were: domiciliary infestation 7.5%, density 2.35, colonization 66.6%, overcrowding 31.33, natural infection 4.6%, and relative infection 2.5%. These results and findings in Peru and Argentina, show that P. rufotuberculatus has a potential success in domiciliation and could some day become an alternate vector of American trypanosomiasis.


Minecoside promotes apoptotic progression through STAT3 inactivation in breast cancer cells.
Breast cancer is one of the most common malignant tumors in women worldwide, and is a major cause of mortality and morbidity in cancer patients. Constitutive activation of STAT3 has been found in a variety of malignant tumors, including breast cancer. Since STAT3 activation is capable of regulating various important features of tumor cells, identification of a novel STAT3 inhibitor is considered a potential strategy for treating breast cancer. The aim of the present study was to examine whether minecoside (MIN), an active compound extracted from Veronica peregrina L., exerts an antitumor effect by inhibiting STAT3 signaling pathway in MDA-MB-231 cells. The results revealed that MIN inhibited the constitutive STAT3 activation in a dose- and time-dependent manner. MIN also blocked the nuclear translocation of STAT3 and suppressed STAT3-DNA binding. In addition, MIN downregulated the STAT3-mediated expression of proteins such as Bcl-xL, Bcl-2, CXCR4, VEGF, and cyclin D1. Subsequently, MIN promoted the caspase-dependent apoptosis in MDA-MB-231 cells. Overall, results of the present study provide evidence that MIN exerted anticancer activity via inhibition of the STAT3 signaling pathway. Further studies using animal models are required to determine the potential of this molecule as an anticancer drug.


[A case of degenerative type of progressive myoclonus epilepsy].
This report describes a patient with degenerative type of progressive myoclonus epilepsy (PME), who showed slowly progressive deterioration of the central nervous system; intellectual impairment, dysarthria, and involuntary movements, particularly action myoclonus and dystonia. The patient was a 19-year-old woman who had no hereditary factors. At the age of 4, she developed action myoclonus in the upper limbs bilaterally. Her condition became gradually worse, and at the age of 15, she was admitted to our hospital because of involuntary movement in the upper limbs. First physical examination revealed mild mental retardation, action myoclonus, dystonia, and delayed adolescence. As giant SEP characteristic of PME and Ramsay Hunt syndrome was found, she was tentatively diagnosed as having Ramsay Hunt syndrome without epilepsy, and delayed adolescence. Now, she is 19 years old, and unable to walk alone because of involuntary movements and paralysis. But she has not developed epilepsy. As she has not been compatible with progressive myoclonus epilepsy (PME) and progressive myoclonic ataxia (PMA) classified by Marseille Consensus Group, she has been diagnosed as having an atypical PME syndrome.


Generating real-world data from health records: design of a patient-centric study in multiple sclerosis using a commercial health records platform.
The FlywheelMS study will explore the use of a real-world health record data set generated by PicnicHealth, a patient-centric health records platform, to improve understanding of disease course and patterns of care for patients with multiple sclerosis (MS). The FlywheelMS study aims to enroll 5000 adults with MS in the United States to create a large, deidentified, longitudinal data set for clinical research. PicnicHealth obtains health records, including paper charts, electronic health records, and radiology imaging files from any healthcare site. Using a large-scale health record processing pipeline, PicnicHealth abstracts standard and condition-specific data elements from structured (eg, laboratory test results) and unstructured (eg, narrative) text and maps these to standardized medical vocabularies. Researchers can use the resulting data set to answer empirical questions and study participants can access and share their harmonized health records using PicnicHealth's web application. As of November 24, 2020, more than 4176 participants from 49 of 50 US states have enrolled in the FlywheelMS study. A median of 200 pages of records have been collected from 14 different doctors over 8 years per participant. Abstraction precision, established through inter-abstractor agreement, is as high as 97.8% when identifying and mapping data elements to a standard ontology. Using a commercial health records platform, the FlywheelMS study is generating a real-world, multimodal data set that could provide valuable insights about patients with MS. This approach to data collection and abstraction is disease-agnostic and could be used to address other clinical research questions in the future.


Dasatinib and chemotherapy in a patient with early T-cell precursor acute lymphoblastic leukemia and NUP214-ABL1 fusion: A case report.
The present study aimed to evaluate the therapeutic efficacy of dasatinib in a patient with nucleoporin 214-tyrosine protein kinase ABL1 proto-oncogene 1 (NUP214-ABL1)-positive early T-cell precursor-acute lymphoblastic leukemia (ETP-ALL), as well as that of selinexor and dasatinib for NUP214-ABL1-positive ETP-ALL in vitro. ETP leukemia is a form of T-cell ALL (T-ALL) with poor prognosis. The NUP214-ABL1 gene is present in ~6% of T-ALL cases, however the prevalence of NUP214-ABL1 gene expression in ETP-ALL in particular has not yet been verified. The current study reports the rare case of a 29-year-old man with ETP-ALL harboring the NUP214-ABL1 fusion gene, presenting with low-grade fever, stomachache and splenomegaly. The patient was successfully treated with dasatinib and vincristine, idarubicin, cyclophosphamide and prednisone (VICP) chemotherapy. The therapeutic efficacy of selinexor and dasatinib was also evaluated in vitro. Apoptosis was analyzed using Annexin V/propidium iodide staining and flow cytometry, and poly ADP-ribose polymerase (PARP) cleavage was detected using western blot analysis. The results demonstrated that the apoptotic cell population significantly increased following selinexor or dasatinib treatment compared with the control (P<0.05). Furthermore, combined selinexor and dasatinib treatment led to a significant increase in cell apoptosis compared with either treatment alone (P<0.05). The apoptosis results were confirmed by PARP cleavage. Thus, NUP214-ABL1 fusion gene expression should be tested in T-ALL, including ETP-ALL. Dasatinib used in combination with traditional induction chemotherapy may reverse the high induction failure of ETP-ALL with NUP214-ABL1 fusion gene; however, further prospective studies are required to confirm this. Therefore, selinexor with or without dasatinib may serve as a potential salvage therapy in the case of relapse and may be developed as a novel treatment for ETP-ALL with the NUP214-ABL1 fusion gene.


Child malnutrition in poor smallholder households in rural Kenya: an in-depth situation analysis.
To investigate the effect of seasonal changes on household food availability on the nutritional status of preschool children from rural households. Households with preschool children were randomly selected from a sampling frame developed from a census list. Data were collected each month or at intervals for 14 months using pre-coded questionnaires. The study was carried out in Njoro division, Nakuru district, Kenya. Subjects comprised 41 preschool children (22 girls and 19 boys) aged between 18 and 36 months. Households with preschool children were listed from a census conducted earlier. A random sample of 45 subjects was selected, out of which 41 completed the study. Food consumption data were collected monthly using the 24-h recall method, and by the 3-day weighed record method during the peak of each season. Subjects were measured once each month, while length was measured at three intervals over the study period. Significant differences in intake of calcium, vitamin A, thiamin and riboflavin were observed between the lean and the post-harvest months, but not with energy, protein, fat, iron, niacin and vitamin C. There were no significant seasonal differences in mean weight changes, which were at the rate of 182 g/month. Mean length increased at a faster rate during the lean season compared to the postharvest months. 51% of the children were stunted during the lean season compared to 28% in the post-harvest months. The results indicate a seasonal influence on energy and nutrient intake among preschoolers from low income rural households in Kenya.


Bacterial lipoproteins may substitute for cytokines in the humoral immune response to T cell-independent type II antigens.
Bacterial lipoproteins share a common structural motif that has been shown to stimulate proliferation and Ig secretion of murine B cells, in a manner distinct from that mediated by LPSs. Studies of lipoprotein-mediated B cell activation utilized heterogeneous populations of lymphoid cells, leaving unresolved their ability to directly activate resting B cells, as well as their ability to interact with other B cell stimuli. Using highly enriched and/or sort-purified resting murine B cells, we demonstrate that, in contrast to previous reports, lipoproteins (lipoprotein-D, lipoprotein-OspA, and/or the synthetic analogue Pam3Cys) stimulate little, if any, proliferation or Ig secretion in resting B cells. However, when combined with a multivalent membrane (m)Ig-mediated cross-linking signal, dextran-conjugated anti-IgD Abs (alpha delta-dex), lipoproteins mediate up to 10,000-fold inductions in IgM secretion and up to 25-fold enhancements in cellular proliferation relative to that observed with alpha delta-dex alone, in the absence of added cytokines. This mIg-mediated enhancement of Ig secretion was not observed when B cells were stimulated with bivalent, unconjugated anti-Ig. CD40 ligand (CD40L), shows a similar, although somewhat more moderate, synergy with lipoproteins for induction of proliferation and IgM secretion. By contrast, lipoproteins by themselves are relatively ineffective at costimulating Ig secretion in the presence of various combinations of cytokines. These data suggest that bacteria may induce Ag-specific humoral immunity through the action of bacterial polysaccharides that mediate an Ag-specific multivalent mIg signal, in concert with bacterial lipoproteins that deliver ancillary signals, without a requirement for recruitment of non-B cell types.


Review of Dissolved Oxygen Detection Technology: From Laboratory Analysis to Online Intelligent Detection.
Dissolved oxygen is an important index to evaluate water quality, and its concentration is of great significance in industrial production, environmental monitoring, aquaculture, food production, and other fields. As its change is a continuous dynamic process, the dissolved oxygen concentration needs to be accurately measured in real time. In this paper, the principles, main applications, advantages, and disadvantages of iodometric titration, electrochemical detection, and optical detection, which are commonly used dissolved oxygen detection methods, are systematically analyzed and summarized. The detection mechanisms and materials of electrochemical and optical detection methods are examined and reviewed. Because external environmental factors readily cause interferences in dissolved oxygen detection, the traditional detection methods cannot adequately meet the accuracy, real-time, stability, and other measurement requirements; thus, it is urgent to use intelligent methods to make up for these deficiencies. This paper studies the application of intelligent technology in intelligent signal transfer processing, digital signal processing, and the real-time dynamic adaptive compensation and correction of dissolved oxygen sensors. The combined application of optical detection technology, new fluorescence-sensitive materials, and intelligent technology is the focus of future research on dissolved oxygen sensors.


A method to determine the speech transmission index from speech waveforms.
A method for computing the speech transmission index (STI) using real speech stimuli is presented and evaluated. The method reduces the effects of some of the artifacts that can be encountered when speech waveforms are used as probe stimuli. Speech-based STIs are computed for conversational and clearly articulated speech in several noisy, reverberant, and noisy-reverberant environments and compared with speech intelligibility scores. The results indicate that, for each speaking style, the speech-based STI values are monotonically related to intelligibility scores for the degraded speech conditions tested. Therefore, the STI can be computed using speech probe waveforms and the values of the resulting indices are as good predictors of intelligibility scores as those derived from MTFs by theoretical methods.


24-month use of once-weekly GH, LB03002, in prepubertal children with GH deficiency.
Sustained-release GH formulations may provide a strategy for improving treatment compliance and persistence in GH-deficient patients. The aim of the study was to examine efficacy and safety of LB03002, a sustained-release GH formulation for once-weekly administration. We conducted a phase III, 12-month, multinational, randomized, open-label, comparator-controlled trial with a 12-month uncontrolled extension. Prepubertal GH treatment-naive GH-deficient children (mean age, 7.8 y) participated in the study. We administered once-weekly LB03002 (n=91) or daily GH (n=87) for 1 year, followed by once-weekly LB03002 for all patients for another year (LB03002 throughout, n=87; switched to LB03002, n=80). Height, height velocity (HV), IGF-1, GH antibodies, and adverse events were determined throughout. Primary analysis was noninferiority of LB03002 vs daily GH at 1 year by analysis of covariance. Mean±SD HV during year 1 was 11.63±2.60 cm/y with LB03002, and 11.97±3.09 cm/y with daily GH, with increases from baseline of 8.94±2.91 and 9.04±3.19 cm/y, respectively. The least square mean HV difference for LB03002 - daily GH was -0.43 cm/y (99% confidence interval, -1.45 to 0.60 cm/y). Mean HV also remained above baseline in year 2 (8.33±1.92 cm/y in the LB03002 throughout group, and 7.28±2.34 cm/y in the switched to LB03002 group). Injection site reactions occurred more frequently in LB03002-treated patients but were considered mild to moderate in >90% of cases. Growth response with once-weekly LB03002 in GH-deficient children is comparable to that with daily GH, achieving expected growth rates for 24 months. Once-weekly LB03002 is a strong candidate for long-term GH replacement in GH-deficient children.


Subinhibitory concentrations of penicillin increase the mutation rate to optochin resistance in Streptococcus pneumoniae.
The aim of this work was to study the effect of subinhibitory concentrations of penicillin, chloramphenicol and erythromycin on the mutation rate of Streptococcus pneumoniae. The mutation rate to rifampicin and optochin resistance was estimated using fluctuation analysis in three capsulated S. pneumoniae strains, cultured both with and without different subinhibitory antibiotic concentrations. The atpAC and rpoB mutations that conferred optochin and rifampicin resistance, respectively, were identified by DNA sequencing. The exposure to subinhibitory concentrations of penicillin increased the mutation rate (expressed as mutation per cell division) to optochin resistance between 2.1- and 3.1-fold for all three strains studied. In contrast, the rifampicin resistance assay showed no significant variations. To analyse the putative cause of the different responses between the optochin and rifampicin tests, mutations that conferred resistance in both cases were analysed. The difference may be explained by the genetic nature of the atpAC mutations, mostly transversions, which are not efficiently repaired by the HexAB mismatch repair system. We demonstrated that subinhibitory concentrations of penicillin significantly increased the mutation rate of S. pneumoniae, suggesting that exposure to this antibiotic could help this pathogen to acquire mutations that confer resistance to other antibiotics. The optochin test was useful to detect this phenomenon and it should be considered for further mutability analysis in S. pneumoniae.


The seductive lure of creative compensation.
In today's booming economy, the experienced development professional is being asked to take a more active role in the management of the organization. Not only is the development professional required to raise money in the traditional sense, but she is also being asked to create programs that will raise money in cyberspace, develop e-commerce ventures and product lines.


Mesophyll Resistances to SO(2) Fluxes into Leaves.
Uptake of label from solutions containing (35)SO(2), H(35)SO(3) (-) and (35)SO(3) (2-) into mesophyll protoplasts, vacuoles, and chloroplasts isolated from young barley leaves was measured at different pH values. Uptake was fast at low pH, when the concentration of SO(2) was high, and low at high pH, when the concentration of SO(2) was low. When the resistance (R) of plasmalemma, tonoplast, and chloroplast envelope to the penetration of SO(2) was calculated from rates of uptake of label, comparable values were obtained for the different biomembranes at low pH values. R was close to 8000 seconds per meter and permeability coefficients were close to 1.25 x 10(-4) meters per second. Under these conditions R may describe resistance to SO(2) diffusion across a lipid bilayer. At higher pH values, R decreased. As R was calculated on the assumption that SO(2) is the only penetrating molecular species, the data suggest that carrier-mediated anion transport contributes to the uptake of sulfur at physiological pH values thereby decreasing apparent R(SO(2) ). The contribution of anion transport appeared to be smaller for transfer across the plasmalemma than for transfer across the tonoplast. It was large for transfer across the chloroplast envelope. The phosphate translocator of the chloroplast envelope catalyzed uptake of SO(3) (2-) into chloroplasts at neutral pH. Uptake was decreased in the presence of high levels of phosphate or sulfate and by pyridoxal phosphate. SO(2) transfer into cells leads to the intracellular liberation of one or two protons, depending on pH and oxidizing conditions. When the divalent sulfite anion is exchanged across the chloroplast envelope, bisulfite formation results in proton uptake in the chloroplast stroma, whereas SO(2) uptake into chloroplasts lowers the stroma pH.


Imbalance of the autonomic nervous system at night in women with gestational diabetes.
Autonomic nervous system dysfunction is observed in Type 2 diabetes. As gestational diabetes is a potent risk factor of later Type 2 diabetes, we set out to determine whether autonomic nervous system imbalance could already be observed in women with this condition. Because activity of the sympathetic nervous system tends to be relatively stable in the nocturnal hours, we performed the study at night. We studied 41 women with gestational diabetes, 22 healthy pregnant controls and 14 non-pregnant controls. We assayed plasma noradrenaline at 24.00, 04.00 and 07.00 h and performed an overnight Holter recording for heart rate variability analysis. In addition, we assayed plasma adrenomedullin, a cardiovascular protective hormone. Compared with non-pregnant controls, plasma noradrenaline levels were increased at 04.00 and 07.00 h in the gestational diabetic (P = 0.003) and pregnant control (P = 0.002) groups, with no difference between them. Heart rate variability, very-low-frequency and low-frequency power were lower in pregnant groups compared to the non-pregnant controls. Heart rate variability remained unchanged between specified sampling times in the gestational diabetic group, in contrast to fluctuation seen in the control groups. Gestational diabetes, compared with normal pregnancy, seems not to be a state of overall sympathetic nervous system activation. At the heart level, however, an inhibitory effect on autonomic nervous system modulation was seen. Plasma noradrenaline and heart rate variability correlated well, supporting the use of this function in future studies of overall sympathetic activity during pregnancy.


A time-of-flight backscattering spectrometer at the Spallation Neutron Source, BASIS.
We describe the design and current performance of the backscattering silicon spectrometer (BASIS), a time-of-flight backscattering spectrometer built at the spallation neutron source (SNS) of the Oak Ridge National Laboratory (ORNL). BASIS is the first silicon-based backscattering spectrometer installed at a spallation neutron source. In addition to high intensity, it offers a high-energy resolution of about 3.5 μeV and a large and variable energy transfer range. These ensure an excellent overlap with the dynamic ranges accessible at other inelastic spectrometers at the SNS.


Clinical validity of cytochrome P450 metabolism and serotonin gene variants in psychiatric pharmacotherapy.
Adverse events, response failures and medication non-compliance are common in patients receiving medications for the treatment of mental illnesses. A systematic literature review assessed whether pharmacokinetic (PK) or pharmacodynamic (PD) responses to 26 commonly prescribed antipsychotic and antidepressant medications, including efficacy or side effects, are associated with nucleotide polymorphisms in eight commonly studied genes in psychiatric pharmacotherapy: CYP2D6, CYP2C19, CYP2C9, CYP1A2, CYP3A4, HTR2C, HTR2A, and SLC6A4. Of the 294 publications included in this review, 168 (57%) showed significant associations between gene variants and PK or PD outcomes. Other studies that showed no association often had insufficient control for confounding variables, such as co-medication use, or analysis of medications not substrates of the target gene. The strongest gene-outcome associations were for the PK profiles of CYP2C19 and CYP2D6 (93% and 90%, respectively), for the PD associations between HTR2C and weight gain (57%), and for SLC6A4 and clinical response (54%), with stronger SLC6A4 response associations for specific drug classes (60-83%). The preponderance of evidence supports the validity of analyzing nucleotide polymorphisms in CYP and pharmacodynamic genes to predict the metabolism, safety, or therapeutic efficacy of psychotropic medications commonly used for the treatment of depression, schizophrenia, and bipolar illness.


Pattern of antenatal care provided at a public sector hospital Hyderabad Sindh.
To assess the pattern of antenatal care provided to the pregnant women and to determine their level of satisfaction for provision of services. This cross-sectional study was conducted at a public sector hospital of Hyderabad Sindh, the data was collected in the month of October 2004. The data was collected by using a pre-tested semi-structured Questionnaire, during the month of October 2004. A total of 161 women consecutively attending antenatal care clinic were included in the study. The variables included were socio-demographic like age, education, occupation and income, maternal and child health variables and level of satisfaction about antenatal care provided. The data was analyzed by using statistical package SPSS version 11. The mean age of women was 29.08 +/- 3.95 years, majority were housewife, 43.5% women were illiterate, 47.2% had primary education and 9.3% had secondary level of education. About 66% were from low-income group, i.e., earning less than 3000 rupees. About 71% were multi gravida, 67% had live births and 32% had history of abortions. Four had history of Intra uterine deaths. Only 22.4% reported that they use contraceptive for spacing. About 50% of the women were dissatisfied with the services available. The reasons identified for dissatisfaction were long waiting time, inadequate medicine supply and incomplete tetanus vaccination were also reported. This study concluded that antenatal care provided needs improvement and require attention to improve the quality of services provided.


[Management of severe stenosis controversies and promises].
In western countries, aortic stenosis is the most common valvular heart disease. A manifestation of ageing, the disorder is becoming more frequent as the average age of the population increases. Symptomatic severe disease is universally fatal if left untreated yet is consistent with a typical lifespan when mechanical relief of the stenosis is provided in a timely fashion. Risk stratification, management of severe asymptomatic disease, and the effect of new percutaneous treatments, provide both controversy and exciting promise to care of patients with aortic stenosis. This review aims to go over some of the most hot issues currently debated on this topic.


Unique vapochromism of a paddlewheel-type dirhodium complex accompanied by dynamic structural and phase transitions.
The one-dimensional coordination polymer [Rh2(HA)4]n (1G; HA = hexanoate) exhibits a drastic vapochromic color change from green to red upon exposure to pyridine (py) vapor. Heating the red discrete complex [Rh2(HA)4(py)2] (1R) at 338 K affords the purple discrete tetrarhodium complex [Rh2(HA)4(py)]2 (1P), which is an intermediate species in the vapochromic transformation of 1G to 1R. The obtained complexes 1G, 1R, and 1P differ not only in their color in the solid state, but also in their temperature-dependent phase transition properties.


Design, Synthesis, and Bioevaluation of Dexmedetomidine Prodrug.
Dexmedetomidine is commonly used in clinical practice as an anesthetic adjuvant and sedative. Unfortunately, major side effects include significant blood pressure fluctuation and bradycardia. Herein, we report the design and synthesis of four series of dexmedetomidine prodrugs aimed to alleviate hemodynamic fluctuations and simplify the administration procedure. From the in vivo experiments, all the prodrugs took effect within 5 min and did not cause significant recovery delay. The increase in blood pressure generated by one bolus of most of the prodrugs (14.57%-26.80%) was similar to that resulting from a 10 min infusion of dexmedetomidine (15.54%), which is significantly lower than the effect from a single dose of dexmedetomidine (43.55%). The decrease in heart rate induced by some prodrugs (-22.88% to -31.10%) was significantly alleviated compared with dexmedetomidine infusion (-41.07%). Overall, our work demonstrates that the prodrug strategy is useful to simplify administration procedures and mitigate hemodynamic fluctuations induced by dexmedetomidine.


The complete set of Toxoplasma gondii ribosomal protein genes contains two conserved promoter elements.
Recently we showed that de novo ribosome biosynthesis is transcriptionally regulated in Coccidia, depending on their life-cycle stage. Since the expression of ribosomal protein genes is likely coordinated, the transcriptional control of all Toxoplasma gondii ribosomal protein (RP) genes was analysed. Therefore, the complete set of all cytoplasmic RPs was defined, containing 79 different RPs in T. gondii. RP genes were randomly distributed over the genome, each with a unique upstream region with the exception of 8 RP genes which were paired in a head-to-head orientation. To study if the RP genes share conserved promoter elements, a database was made containing upstream sequences of all T. gondii RP genes. Promoter activity was confirmed for the upstream sequences of 8 RP genes, some of which are comparable in strength to the alpha-tubulin promoter. In the complete set of RP upstream sequences 2 novel and highly conserved elements were identified, named Toxoplasma Ribosomal Protein (TRP)-1 (consensus: TCGGCTTATATTCGG) and TRP-2 ([T/C]GCATGC[G/A]). TRP-1 and/or TRP-2 were present in 95% of all RP upstream sequences and moreover, were specifically localized in a small region near the presumptive transcriptional start site (10-330 bp upstream). Although TRP elements were mostly absent in known T. gondii promoters, they are present elsewhere in the T. gondii genome suggesting that they operate not only in RP genes but in a larger set of genes. The identification of TRP elements creates a basis to further study the underlying mechanism by which RP transcription is controlled in T. gondii.


Longitudinal Assessment of Retinal Thinning in Adults With and Without Sickle Cell Retinopathy Using Spectral-Domain Optical Coherence Tomography.
Determination of retinal thinning rates may help to identify patients who are at risk of progression of sickle cell retinopathy. To assess the rates of macular thinning in adults with and without sickle cell retinopathy using spectral-domain optical coherence tomography (OCT) and to identify ocular and systemic risk factors associated with retinal thinning. This longitudinal prospective case-control study enrolled adult participants from a university-based retina subspecialty clinic between February 11, 2009, and July 3, 2019. The study was designed in autumn 2008 and conducted from February 2, 2009, to July 3, 2020. Participants with sickle cell retinopathy (sickle cell group) were matched by age and race with participants without sickle cell retinopathy (control group). Participants received annual spectral-domain OCT and clinical examinations. Those with at least 1 year of follow-up by July 3, 2020, were included in the analysis. Data were analyzed from February 2, 2009, to July 3, 2020. The primary outcome was comparison of spectral-domain OCT measurements from early-treatment diabetic retinopathy study subfield rates of retinal thinning between eyes with and without sickle cell retinopathy and between different sickle cell hemoglobin subtypes. The secondary outcome was identification of ocular and systemic risk factors associated with rates of retinal thinning. Among 370 adults (711 eyes) enrolled in the study, 310 participants (606 eyes) had sickle cell retinopathy, and 60 participants (105 eyes) did not. Of those, 175 of 310 participants (56.5%; 344 of 606 eyes [56.8%]; mean [SD] age, 37.8 [12.8] years; 126 women [72.0%]) in the sickle cell group and 31 of 60 participants (51.7%; 46 of 105 eyes [43.8%]; mean [SD] age, 59 [15.4] years; 22 women [71.0%]) in the control group had at least 1 year of clinical and spectral-domain OCT follow-up data from baseline. The mean (SD) follow-up was 53.7 (32.6) months for the sickle cell group and 54.6 (34.9) months for the control group. Rates of macular thinning in the sickle cell group were significantly higher than those in the control group for the inner nasal (difference, -1.18 μm per year; 95% CI, -1.71 to -0.65 μm per year), inner superior (difference, -1.03 μm per year; 95% CI, -1.78 to -0.29 μm per year), inner temporal (difference, -0.61 μm per year; 95% CI, -1.16 to -0.07 μm per year), and outer nasal (difference, -0.41 μm per year; 95% CI, -0.80 to -0.03 μm per year) quadrants. Patients with sickle cell hemoglobin SC and sickle cell hemoglobin β-thalassemia subtypes had higher rates of retinal thinning than those with the sickle cell hemoglobin SS subtype. Risk factors associated with greater rates of retinal thinning included participant age, stage of retinopathy, previous stroke, and presence of hypertension, acute chest syndrome, or diabetes. Hydroxyurea therapy was associated with decreased rates of retinal thinning and may be a protective factor. In this study, rates of retinal thinning were higher among participants with sickle cell retinopathy compared with those without sickle cell retinopathy, and thinning rates increased with participant age and stage of retinopathy. These findings suggest that identifying anatomic worsening of sickle cell maculopathy through spectral-domain OCT may be a useful parameter to evaluate the progression of sickle cell retinopathy.


A Randomized, Double-blind Study of Amorolfine 5% Nail Lacquer with Oral Fluconazole Compared with Oral Fluconazole Alone in the Treatment of Fingernail Onychomycosis.
It is a challenge to treat onychomycosis due to frequent treatment failures and relapses. Systemic and topical therapies need to be combined to improve cure rates. Antifungal susceptibility might play a role in the treatment resistance of onychomycosis. To compare the safety and effectiveness of amorolfine 5% nail lacquer + oral fluconazole versus only oral fluconazole in the treatment of fingernail onychomycosis. In this double-blind trial (CTRI/2015/02/005369), patients were randomized (1:1) into amorolfine 5% nail lacquer + fluconazole and dummy lacquer + fluconazole. Treatment was given for 3 months with monthly follow-ups. Antifungal sensitivity was carried out for Candida. Effectiveness was assessed by reduction in the number and percentage area of nails involved and mycological cure. At the end of 3-month treatment period, the association between drug sensitivity and treatment response was explored for the Candida infections. Among 30 study participants, the combination group showed significantly lower number of nail involvement (P = 0.004) and percentage nail involvement (P = 0.005) than only fluconazole group. Pretreatment fungal culture showed a comparable number of dermatophytes, Candida, Aspergillus in both the groups. Sensitivity testing was done for the isolated Candida species. Antifungal sensitivity for Candida (n = 11) was tested, and 8 (72.7%) of the organisms were sensitive to fluconazole (minimum inhibitory concentration [MIC] 1.25 ± 1.19 μg/ml), 100% were sensitive to itraconazole (MIC 0.0726 ± 0.021 μg/ml), and 3 (27.3%) were susceptible-dose dependent (S-DD) to fluconazole (MIC 16 μg/ml). Fluconazole only group patients with Candida who showed resistance to fluconazole did not respond to therapy; however, patients in the combination group showed moderate improvement (reduction in area involvement = 55.56 ± 35.36%). The combination of amorolfine/fluconazole achieved a higher cure rate not only for sensitive fungus but also for those which were S-DD to fluconazole.


Visual-Text Reference Pretraining Model for Image Captioning.
People can accurately describe an image by constantly referring to the visual information and key text information of the image. Inspired by this idea, we propose the VTR-PTM (Visual-Text Reference Pretraining Model) for image captioning. First, based on the pretraining model (BERT/UNIML), we design the dual-stream input mode of image reference and text reference and use two different mask modes (bidirectional and sequence to sequence) to realize the VTR-PTM suitable for generating tasks. Second, the target dataset is used to fine tune the VTR-PTM. To the best of our knowledge, VTR-PTM is the first reported pretraining model to use visual-text references in the learning process. To evaluate the model, we conduct several experiments on the benchmark datasets of image captioning, including MS COCO and Visual Genome, and achieve significant improvements on most metrics. The code is available at https://github.com/lpfworld/VTR-PTM.


Cloning and characterization of tek, the gene encoding the major extracellular protein of Pseudomonas solanacearum.
Susceptible plants infected by Pseudomonas solanacearum usually will, largely due to extracellular proteins (EXPs) and the high-molecular-mass extracellular polysaccharide (EPS I) this pathogen produces. Circumstantial evidence suggested that a 28-kDa protein, the single most abundant EXP made by P. solanacearum in culture, is associated with production of EPS I, and thus might have a role in pathogenesis. The 28-kDa EXP was purified and, based on its N-terminal amino acid sequence, an oligonucleotide mixture was made and used as a hybridization probe to clone the gene encoding it. DNA sequence analysis suggested that the coding sequence for the 28-kDa EXP is within a gene, designated tek, that encodes a 58-kDa membrane-associated precursor protein that is processed by signal peptidase II during export. Analysis of radiolabeled polypeptides expressed from tek confirmed that it encodes a 58-kDa precursor protein, which is exported out of the cells as a 55-kDa preprotein and processed extracellularly to release the very basic 28-kDa EXP from its C terminus. The position, transcriptional direction, and regulated expression of tek suggest that it is cotranscribed with xpsR, a gene essential for regulating biosynthesis of EPS I, and reinforces the association of the 28-kDa EXP with virulence. However, since P. solanacearum mutants lacking only the 28-kDa EXP produced wild-type amounts of EPS I and were fully virulent, the function of this protein remains unclear.


Effect of mild α-chymotrypsin treatment of highly viscous semen samples on fertilization rates.
Highly viscous semen reduces sperm motility significantly and can contribute to infertility. When processing semen samples, few techniques exist to induce liquefaction in case of seminal hyperviscosity such as different washing steps and mechanical treatment. The use of α-chymotrypsin seems controversial due to possible negative effects on fertilisation rates after in vitro fertilization (IVF). The main objective of this study was to examine the influence of mild α-chymotrypsin treatment of semen samples on the fertilisation rate after artificial reproductive treatment (ART). The fertilization rate of 52 ART cycles was examined following IVF using a low dose of α-chymotrypsin to induce liquefaction of highly viscous semen and was compared to a control group of 88 ART cycles. There was no significant difference in the fertilization rates of α-chymotrypsin treated semen samples compared to the control group; pregnancy rates were unaffected. The use of mild α-chymotrypsin treatment of semen samples in case of hyperviscosity does not appear to impact negatively on the fertilization rates after ART and could be regarded as an additional method to induce liquefaction of highly viscous semen samples in IVF.


Muscle precursor cells invade and repopulate freeze-killed muscles.
A problem with the use of muscle grafting as a therapeutic procedure is to produce a graft functionally adequate to replace a muscle of complex architecture, such as a sphincter muscle. We thought it might be possible to use dead cadaver muscles, repopulated by the patient's own muscle precursor cells (mpc), to reconstruct muscles whose anatomy would be imposed by the framework of dead muscle and whose genetic constitution would be determined by the mpc. Here we show, in the mouse, that an extensor digitorum longus (EDL) muscle, killed by repeated freezing and thawing, repopulated with mpc and grafted into a nu/nu or tolerant AKR host mouse, is capable of supporting muscle formation. By using the allotypic isoenzyme forms of glucose-6-phosphate isomerase as markers, we have shown that the newly regenerated muscle in such grafts is derived mainly from the implanted mpc, but also to some extent from the host mouse's own mpc. By 50-70 days after grafting, new muscle fibres were found to constitute up to 70% of the graft. Many fibres had assumed diameters in the normal range for mouse muscle, often having peripherally placed nuclei. These findings raise the possibility of the therapeutic use of such grafts. To our surprise, dead EDL muscle grafts into which no mpc had been implanted were also the site of good muscle regeneration. New-formed muscle in these grafts was shown to be derived entirely from mpc which must have migrated into the graft from the host. Investigation of the mechanisms underlying this phenomenon should further our knowledge of factors which regulate the proliferation and movement of dormant mpc in adult animals.


Some methods of assaying inhibitors of cell proliferation.
Inhibition of cell proliferation by leucocyte extracts containing the granulocytic chalone has been monitored in various ways. Target cells were rat bone marrow cells and chloroleukaemia cells cultured on cover glasses, as well as mouse marrow cells cultured in vivo and in vitro in diffusion chambers. Provided that the technique is optimized, the in vitro rat cell assays yielded reliable results with different types of radioactive DNA precursors. With the diffusion chamber techniques cells synthesizing DNA were killed specifically by hydroxyurea, rather than labelling them with e.g. 3H-thymidine. Inhibition of proliferation then showed up as a decreased cell killing, as compared with the controls. Inhibition of proliferation of both progenitor and transit cells could be demonstrated in this way, without interference by added thymidine.


Biomechanical characterization of the small intestine to simulate gastrointestinal tract chyme propulsion.
Regular intestinal motility is essential to guarantee complete digestive function. The coordinative action and integrity of the smooth muscle layers in the small intestine's wall are critical for mixing and propelling the luminal content. However, some patients present gastrointestinal limitations which may negatively impact the normal motility of the intestine. These patients have altered mechanical and muscle properties that likely impact chyme propulsion and may pose a daily scenario for long-term complications. To better understand how mechanics affect chyme propulsion, the propulsive capability of the small intestine was examined during a peristaltic wave along the distal direction of the tract. It was assumed that such a wave works as an activation signal, inducing peristaltic contractions in a transversely isotropic hyperelastic model. In this work, the effect on the propulsion mechanics, from an impairment on the muscle contractile ability, typical from patients with systemic sclerosis, and the presence of sores resultant from ulcers was evaluated. The passive properties of the constitutive model were obtained from uniaxial tensile tests from a porcine small intestine, along with both longitudinal and circumferential directions. Our experiments show decreased stiffness in the circumferential direction. Our simulations show decreased propulsion forces in patients in systemic sclerosis and ulcer patients. As these patients may likely need medical intervention, establishing action concerning the impaired propulsion can help to ease the evaluation and treatment of future complications.


Is air temperature at birth associated with body mass index in 9-10 year-old children?
Several studies suggest that temperature (season) at birth affects body weight and obesity years later. This study related air temperature at birth to body mass index in Liverpool primary school children (n = 11,084). No association was found between body mass index categories and month or season of birth and only weak correlations with month of birth and air temperature at birth. These correlations disappeared when controlled for precise age and an index of deprivation but girls in the third quintile for deprivation had a higher body mass index if born in colder weather.


Vertical stratification of the air microbiome in the lower troposphere.
The troposphere constitutes the final frontier of global ecosystem research due to technical challenges arising from its size, low biomass, and gaseous state. Using a vertical testing array comprising a meteorological tower and a research aircraft, we conducted synchronized measurements of meteorological parameters and airborne biomass (n = 480) in the vertical air column up to 3,500 m. The taxonomic analysis of metagenomic data revealed differing patterns of airborne microbial community composition with respect to time of day and height above ground. The temporal and spatial resolution of our study demonstrated that the diel cycle of airborne microorganisms is a ground-based phenomenon that is entirely absent at heights >1,000 m. In an integrated analysis combining meteorological and biological data, we demonstrate that atmospheric turbulence, identified by potential temperature and high-frequency three-component wind measurements, is the key driver of bioaerosol dynamics in the lower troposphere. Multivariate regression analysis shows that at least 50% of identified airborne microbial taxa (n = ∼10,000) are associated with either ground or height, allowing for an understanding of dispersal patterns of microbial taxa in the vertical air column. Due to the interconnectedness of atmospheric turbulence and temperature, the dynamics of microbial dispersal are likely to be impacted by rising global temperatures, thereby also affecting ecosystems on the planetary surface.


Mineralization in rat metaphyseal bone exhibits a circadian stage dependency.
Density gradient fractionation analysis of rat metaphyseal bone was used to delineate the biorhythmic changes in bone matrix mineralization. Seventy-two 4-week-old rats were entrained to 12-hr light, 12-hr dark cycles (light, 0800-2000 hr; darkness, 2000-0800 hr) for 4 weeks. All animals were fed ad lib. on Purina laboratory rat chow and tap water. Groups of 10-12 rats were killed by cervical dislocation at 4-hr intervals during a 24-hr period, and the tibias were then biopsied and frozen in liquid N2. Metaphyseal bone was fractionated via bromoformtoluene density gradients into specific gravity fractions ranging from 1.7 to 2.8. Density gradient fractions were analyzed for concentrations of calcium and inorganic phosphorus. Chronograms indicated that the accumulation of both calcium and inorganic phosphorus into the newly forming/least-dense mineral moieties of bone (1.3-1.7 sp grav) showed a single peak in the biorhythm of the rat. A statistically significant circadian rhythm of mineralization was detected for calcium (P less than 0.001) and inorganic phosphorus (P less than 0.039), with peaks during the environmental dark span. These results suggest that the physiological phasing of bone mineralization in the light-dark synchronized rat, is similar to that previously noted for cartilage mineralization and is antiphasal to the midday peak in bone collagen synthesis.


Evidence for sltA1 as a salt-sensitive allele of the arginase gene (agaA) in the ascomycete Aspergillus nidulans.
Strains of Aspergillus nidulans carrying the sltA1 mutation, conferring sensitivity to KCl and NaCl, also showed an arginine-sensitive phenotype whereby concentrations of the L-amino acid at or above 10 mM were toxic to growth. Sexual progeny of a cross between a sltA1 mutant and a wild-type strain showed a co-segregation of salt and arginine sensitivity. Similarly, revertants to salt tolerance showed a loss of arginine sensitivity as did sltA1 strains that were transformed with a cosmid carrying the putative sltA1+ wild-type allele. In addition, arginine sensitivity could be relieved by L-ornithine. It is suggested that sltA1 is a salt-sensitive allele of the arginase gene (agaA).


[Acute pulmonary thromboembolism complicating lung lobectomy; report of a case].
Acute pulmonary thromboembolism is fatal if the diagnosis and treatments are delayed. Here we present a case of acute thromboembolism to the right and left pulmonary arteries after right lung lobar resection. A 52-year-old woman who admitted to our hospital with lung cancer was performed right upper lobectomy with mediastinal lymph node dissection (pT1N0M0, well differentiated adenocarcinoma). Two days after surgery, she complained sudden chest discomfort and dyspnea. The blood pressure and oxygen saturation were rapidly decreased. Because there was no lung edema or atelectasis in the chest portable roentgenogram and no ischemic change in the electrocardiogram, pulmonary thromboembolism was suspected and emergency chest computed tomography (CT) was performed. The CT showed left and right pulmonary arterial thromboembolism and immediate anti-coagulator therapy was started. Her condition was improved and chest CT, which was performed three days after the onset of the thromboembolism, showed decreased but still remained thrombus. The anti-coagulator therapy was continued and one month after the onset of the thromboembolism, thrombus was disappeared on chest CT. She is doing well 17 months after surgery. Early diagnosis and treatments are critical for the pulmonary thromboembolism.


[Expression and characterization of a novel ω-transaminase from Burkholderia phytofirmans PsJN].
Production of chiral amines and unnatural amino-acid using ω-transaminase can be achieved by kinetic resolution and asymmetric synthesis, thus ω-transaminase is of great importance in the synthesis of pharmaceutical intermediates. By genomic data mining, a putative ω-transaminase gene hbp was found in Burkholderia phytofirmans PsJN. The gene was cloned and over-expressed in Escherichia coli BL21 (DE3). The recombinant enzyme (HBP) was purified by Ni-NTA column and its catalytic properties and substrate profile were studied. HBP showed high relative activity (33.80 U/mg) and enantioselectivity toward β-phenylalanine (β-Phe). The optimal reaction temperature and pH were 40 ℃ and 8.0-8.5, respectively. We also established a simpler and more effective method to detect the deamination reaction of β-Phe by UV absorption method using microplate reader, and demonstrated the thermodynamic property of this reaction. The substrate profiling showed that HBP was specific to β-Phe and its derivatives as the amino donor. HBP catalyzed the resolution of rac-β-Phe and its derivatives, the products (R)-amino acids were obtained with about 50% conversions and 99% ee.


The evolution of mechanisms to produce phenotypic heterogeneity in microorganisms.
In bacteria and other microorganisms, the cells within a population often show extreme phenotypic variation. Different species use different mechanisms to determine how distinct phenotypes are allocated between individuals, including coordinated, random, and genetic determination. However, it is not clear if this diversity in mechanisms is adaptive-arising because different mechanisms are favoured in different environments-or is merely the result of non-adaptive artifacts of evolution. We use theoretical models to analyse the relative advantages of the two dominant mechanisms to divide labour between reproductives and helpers in microorganisms. We show that coordinated specialisation is more likely to evolve over random specialisation in well-mixed groups when: (i) social groups are small; (ii) helping is more "essential"; and (iii) there is a low metabolic cost to coordination. We find analogous results when we allow for spatial structure with a more detailed model of cellular filaments. More generally, this work shows how diversity in the mechanisms to produce phenotypic heterogeneity could have arisen as adaptations to different environments.


Acute, subchronic and withdrawal sleep EEG changes during treatment with paroxetine and amitriptyline: a double-blind randomized trial in major depression.
Paroxetine (30 mg), a selective serotonin (5-HT) reuptake inhibitor, was compared in a double-blind trial to amitriptyline (150 mg) in a sample of 40 inpatients aged 18-65 years who fulfilled Research Diagnostic Criteria for major depression. Patients were studied after a placebo drug washout period of 10 days and after an active 4-week treatment period. Sleep EEG recordings were performed before and at the end of the study as well as during acute treatment (first 2 days) and following withdrawal of active medication. Paroxetine shows an antidepressant effect similar to amitriptyline with a different side-effect profile typical of 5-HT reuptake inhibition. Paroxetine and amitriptyline decreased the amount of REM sleep, a well-known effect of classical antidepressants. Paroxetine also shared with other 5-HT reuptake inhibitors an alerting effect on sleep that was not shown to be detrimental on subjective sleep quality.


Chemical and Electrochemical Synthesis of Polypyrrole Using Carrageenan as a Dopant: Polypyrrole/Multi-Walled Carbon Nanotube Nanocomposites.
In this article, iota-carrageenan (IC) and kappa-carrageenan (KC) are used as dopants for the chemical and electrochemical synthesis of polypyrrole (PPy). The composites of chemically synthesized PPy with multi-walled carbon nanotubes (MWNTs) were prepared using an in situ technique. Both the dialyzed and non-dialyzed IC and KC were used as dopants for electrochemical polymerization of pyrrole. Chemically synthesized PPy and PPy/MWNTs composites were studied by ultraviolet visible (UV-vis) absorption spectra to investigate the effect of the concentration and the incorporation of MWNTs. In addition, the electrical, thermal, mechanical, and microscopic characterizations of these films were performed to examine the effect of the dopants and MWNTs on these properties, along with their surface morphology. The films of electrochemically polymerized PPy were characterized using UV-vis absorption spectra, scanning electron microscopy, and cyclic voltammetry (CV). The results were then compared with the chemical polymerized PPy.


Prediction of IFN-gamma regulated gene transcription.
IFN-gamma, a cytokine promoting cell-mediated immunity and antiviral effects, regulates the expression of a large set of genes involved in the immune response. Based on logistic regression, an in silico model for predicting IFN-gamma regulated transcription has been developed by scoring the transcription factor binding sites on the putative promoters of regulated versus not regulated genes derived from the microarray data of IFN-gamma treated human macrophages. The model effectively discriminates the transcription factor binding sites that confer responsiveness to IFN-gamma from those that do not. The model has 65% true positive and 22% false positive rates when evaluated on a small validation set. In order to identify potential IFN-gamma regulated genes in the whole genome, the model has been used to screen 13,668 promoter pairs of human-mouse orthologs/homologs from Ensembl, and 1,387 of them were predicted to be potentially regulated by IFN-gamma. In the pilot experiment, the regulation pattern of a subset of predicted genes that were not detected by microarray approach was evaluated by quantitative PCR. The results for the four novel genes, which are up regulated by IFN-gamma in human macrophages and identified by this approach, are described in the present communication.


[Clinical evaluation of structural fat tissue graft (Lipostructure) in volumetric facial restoration with face-lift. About 100 cases].
Adipose tissue has been used for volume restoration for over a century. Coleman's Lipostructure is a recent procedure for adipocyte transfer, based on strict methodology and the use of specific material. Our aim in this work is to provide an answer to several questions: what is the place of this technique in the restoration of facial volumes? Do aesthetic subunits have an impact on the result? This retrospective study concerned 100 patients who had undergone volumetric facial restoration with face-lift and Lipostructure. A five-member jury carried out subjective evaluation through a questionnaire sent to the patients, and objective evaluation by assessment of pre- and postoperative photographs. Mean time since surgery was 15 months. Overall patient satisfaction was 82% with a mean score of 15/20 on subjective evaluation and of 13.3/20 on objective evaluation. The results differed significantly according to the facial aesthetic subunit involved, the best results being obtained in the malar region and the cheek, and the least satisfactory in the upper and lower lips. This technique has few drawbacks. Prolonged oedema is the only complication (8%). We consider that at the present time Lipostructure is the best means of restoring facial volume. It is a simple, effective and reproducible technique. Its application in all fields of plastic surgery is an essential adjunct to our specialty.


Groin hernia subtypes are associated in patients with bilateral hernias: a 14-year nationwide epidemiologic study.
To investigate the relation between groin hernia subtypes in patients operated for bilateral hernias. With data from the Danish Hernia Database, we identified all patients operated for primary groin hernias from 1998 to 2012. Within this cohort all patients that were bilaterally operated were analyzed. Risk factors for bilateral groin hernia operation as well as the relationship between groin hernia subtypes bilaterally, were analyzed using multivariate Cox proportional hazards analysis and Kappa statistics. A total of 108, 775 persons with primary groin hernia repair (89.9% males) were registered, and of those were 12,041 persons operated bilaterally (94.9% males). Females and males operated for a unilaterally direct inguinal hernia (DIH) had increased Hazard Ratios (HR) of 3.85 (CI 95% 2.14-6.19) and 4.46 (CI 95% 2.57-7.88) of being contralaterally operated for a DIH. Females and males operated for a unilaterally indirect inguinal hernia (IIH) had HRs of 6.93 (CI 95% 3.66-13.11) and 1.89 (CI95% 1.24-2.88) for being contralaterally operated for an IIH. The same tendency was seen for femoral hernias. All hernia subtypes were bilaterally associated in both genders and the hernia subtypes could be localized manifestations of generalized conditions or inheritable traits instead of localized defects.


Thrombospondin 1 is a tight-binding competitive inhibitor of neutrophil cathepsin G. Determination of the kinetic mechanism of inhibition and localization of cathepsin G binding to the thrombospondin 1 type 3 repeats.
Thrombospondin 1 was recently shown to bind to and inhibit the activity of neutrophil elastase (Hogg, P. J., Owensby, D. A., Mosher, D. F., Misenheimer, T. M., and Chesterman, C. N. (1993) J. Biol. Chem. 268, 7139-7146). This finding led us to question whether thrombospondin 1 also binds and inhibits the other major serine proteinase of neutrophils, cathepsin G. In a competitive binding assay, cathepsin G bound to thrombospondin 1 reversibly and saturably with a dissociation constant in the low nanomolar range. The kinetic mechanism of inhibition of cathepsin G activity by thrombospondin 1 was determined using the synthetic cathepsin G substrate, Suc-Ala-Ala-Pro-Phe-p-nitroanilide, and is consistent with hyperbolic tight-binding inhibition in which thrombospondin 1 binds cathepsin G and the Michaelis cathepsin G-substrate complex and weakens, but does not abolish, the efficiency of hydrolysis of Suc-Ala-Ala-Pro-Phe-p-nitroanilide. In the presence of 2 mM calcium ions, 2.9 +/- 0.4 mol of cathepsin G interacted with 1 mol of thrombospondin 1 trimer with a site-binding constant of 7.0 +/- 3.5 nM, which reduced the efficiency of hydrolysis of Suc-Ala-Ala-Pro-Phe-p-nitroanilide 8.5 +/- 1.4-fold. A lower limit for the on rate constant of 5 x 10(6) M-1 S-1 was established. The affinity of binding and stoichiometry for the interaction between cathepsin G and thrombospondin 1 was enhanced in the absence of calcium ions. In the presence of EDTA, 5.3 +/- 0.5 mol of cathepsin G interacted with 1 mol of thrombospondin 1 with a site-binding constant of 2.1 +/- 1.6 nM, implying the existence of two binding sites for cathepsin G on each subunit of thrombospondin 1, one or both of which is variably exposed and sensitive to calcium ions. Thrombospondin 1 protected fibronectin from cleavage by cathepsin G and blocked cathepsin G-mediated platelet aggregation. In summary, the binding of cathepsin G to thrombospondin 1 is tight, reversible, and close enough to the active site of cathepsin G to perturb the interactions of a small synthetic substrate and exclude a macromolecular protein substrate and platelets. Using defined proteolytic fragments and different conformers of thrombospondin 1, the binding sites for cathepsin G have been localized to the thrombospondin 1 type 3 repeats.


Comparison of two different vascular delay methods in a rat cranial epigastric perforator flap model.
The effectiveness of vascular delay in transverse rectus abdominis muscle flaps has been demonstrated in many studies. In deep inferior epigastric perforator flaps, however, the effectiveness of ligation of deep versus superficial epigastric vessels in producing delay is unclear. Using a rat model, we compared ligation of deep and superficial vessels with each other and with a (nondelayed) control group (n = 10). One vascular delay group (n = 10) had ligation of the contralateral cranial epigastric vessels (homolog to the human deep inferior epigastric vessels); the other (n = 10) had ligation of contralateral superficial inferior epigastric vessels. One week later, cranial epigastric perforator flap elevation was performed. Both vascular techniques were effective in producing delay, and there was no statistically significant difference between the 2 groups. Ligation of superficial inferior epigastric vessels, deep inferior epigastric vessels, or both, at least 1 week prior to the deep inferior epigastric perforator flap elevation may increase the usable skin paddle area in humans.


A comparison of hypertensive and nonhypertensive coronary care patients' cardiovascular responses to visitors.
Patients with and without hypertension in a coronary care unit (n = 24) were compared with respect to cardiovascular responses to both a family visit and an interview by an investigator. Variables for each of the four cardiovascular indicators (systolic blood pressure, diastolic blood pressure, heart rate, and premature ventricular contractions) included the value before, the highest value during, the lowest value during, and the value after each social interaction condition. The highest group means for systolic blood pressure and heart rate were significantly higher for patients with hypertension than for patients without hypertension under both the interview and visit conditions. Differences in cardiovascular responses were not significantly greater for family visits than for interviews for patients with hypertension compared with those without hypertension. Thus, although hypertensive patients had greater cardiovascular reactivity to both social interaction conditions than nonhypertensive patients in the coronary care unit, family visits were no more physiologically stressful than a comparative interaction condition.


The cerebellum: it's about time! But timing is not everything--new insights into the role of the cerebellum in timing motor and cognitive tasks.
Converging evidence from different research studies supports a role for the cerebellum in timing neural processes. The cerebellum is part of a distributed system for motor control. The timing hypothesis provides a specific functional role for the unique contribution of the cerebellum. The timing capabilities of the cerebellum appear to extend beyond motor control into tasks focusing on perceptual processing that require the precise representation of temporal information and sensorimotor learning. Behavioral and modeling studies suggest that the cerebellar timing system is best characterized as providing a near-infinite set of interval-type timers rather than as a single clock with pacemaker or oscillatory properties, but this is controversial. In addition to learning precisely timed motor responses, the cerebellum is involved in on-line processing using feed-forward systems for which sensory input is used prior to movement execution to improve movement accuracy. This would be a mechanism for triggering accurate "time." The cerebellum continues to fascinate scientists, and although survival is possible without the cerebellum, the resultant quality of life is significantly compromised with clumsiness, ataxia, hypotonia, dysarthria, slowing of various cognitive perceptual processes, and impaired fine motor and ocular-motor coordination. The last three decades have seen the development of research that has focused on how the cerebellum functions. Further neurophysiologic research in cerebellar cortical neurotransmission is likely to further our understanding of the cerebellar contribution to timing sensorimotor processes.


Stereomicroscopic evaluation of defects caused by torsional fatigue in used hand and rotary nickel-titanium instruments.
The aim of this study was to evaluate defects caused by torsional fatigue in used hand and rotary nickel-titanium (Ni-Ti) instruments by stereomicroscopic examination. One hundred five greater taper Ni-Ti instruments were used including Protaper universal hand (Dentsply Maillefer, Ballaigues, Switzerland), Protaper universal rotary (Dentsply Maillefer, Ballaigues, Switzerland), and Revo-S rotary (MicroMega, Besançon, France) files. Files were used on lower anterior teeth. After every use, the files were observed with both naked eyes and stereomicroscope at 20× magnification (Olympus, Shinjuku, Tokyo, Japan) to evaluate defects caused by torsional fatigue. Scoring was assigned to each file according to the degree of damage. The results were statistically analyzed using the Mann-Whitney U test and the Kruskal-Wallis test. A greater number of defects were seen under the stereomicroscope than on examining with naked eyes. However, the difference in methods of evaluation was not statistically significant. Revo-S files showed minimum defects, while Protaper universal hand showed maximum defects. The intergroup comparison of defects showed that the bend in Protaper universal hand instruments was statistically significant. Visible defects in Ni-Ti files due to torsional fatigue were seen by naked eyes as well as by stereomicroscope. This study emphasizes that all the files should be observed before and after every instrument cycle to minimize the risk of separation.


[Ambulatory diagnosis of patients requiring a pleural biopsy. Study of 100 consecutive cases].
Our aim was to describe our experience with outpatients requiring pleural biopsy. The first 100 patients with pleural exudate from whom at least one pleural biopsy specimen was taken on an outpatient basis at our hospital since January 1993. Clinical and radiological signs were recorded for all patients. We also analyzed complications, frequency of use of other diagnostic test and time required for diagnosis. The mean age of the 100 patients (64 men) was 56 years. Outpatient study of these patients was not prevented by the advanced age on the sample (with 35 patients older than 79), the size of the pleural effusions (23 of which were large), or the diagnosis of diseases with poor prognoses (with 43 effusions diagnosed as neoplastic). Complications encountered in taking the biopsy specimens were similar to those reported for other series. The mean time until diagnosis was 7.4 days. Biopsies can often be obtained from patients with pleural effusion on an outpatient basis, even when clinical symptoms vary widely, without increasing the number of complications and within a reasonable period of time.


Equivalency of the quality of sublethal lesions after photons and high-linear energy transfer ion beams.
The quality of the sublethal damage (SLD) after irradiation with high-linear energy transfer (LET) ion beams was investigated with low-LET photons. Chinese hamster V79 cells and human squamous carcinoma SAS cells were first exposed to a priming dose of different ion beams at different LETs at the Heavy Ion Medical Accelerator in the Chiba facility. The cells were kept at room temperature and then exposed to a secondary test dose of X-rays. Based on the repair kinetics study, the surviving fraction of cells quickly increased with the repair time, and reached a plateau in 2-3 h, even when cells had received priming monoenergetic high-LET beams or spread-out Bragg peak beams as well as X-ray irradiation. The shapes of the cell survival curves from the secondary test X-rays, after repair of the damage caused by the high-LET irradiation, were similar to those obtained from cells exposed to primary X-rays only. Complete SLD repairs were observed, even when the LET of the primary ion beams was very high. These results suggest that the SLD caused by high-LET irradiation was repaired well, and likewise, the damage caused by the X-rays. In cells where the ion beam had made a direct hit in the core region in an ion track, lethal damage to the domain was produced, resulting in cell death. On the other hand, in domains that had received a glancing hit in the low-LET penumbra region, the SLD produced was completely repaired.


Terahertz emission in ladder plus Y-configurations in double quantum dot structure.
The ladder plus Y-double quantum dot (QD) structure has been proposed to improve the second-order nonlinear susceptibility (SONS) under applied electric field. For this purpose, the wetting layer (WL) and QD inhomogeneity contribution in SONS has been considered. In addition, the structure size effect, energy level separation, momentum matrix elements, and pump detuning have been examined, and show that the SONS is increased by using the WL, a low momentum matrix element of WL-QD transition in comparison with interdot transition while QD inhomogeneity reduces SONS to half. This work is predicted to play a key role in terahertz applications, since the frequency emissions obtained are in the range of 75.5-600 μm.


Concurrent use of 5% natamycin and 2% econazole for the management of fungal keratitis.
To determine if concurrent use of 5% natamycin and 2% econazole offers greater benefits than monotherapy with 5% natamycin for the management of fungal keratitis. Subjects presenting to the cornea service were treated with 5% natamycin and 2% econazole used concurrently. We compared the results with a historical control of patients treated with 5% natamycin in the same calendar year. The same clinical and examination protocol including inclusion and exclusion criteria was used for both groups. We compared results of 47 subjects on concurrent use of 5% natamycin and 2% econazole with all 53 subjects who had received 5% natamycin in a previous study (historical controls). Baseline characteristics were similar between the 2 groups. There were no significant differences (P=0.9) between the 2 arms for success (defined as a healed or healing ulcer). Concurrent use of 5% natamycin and 2% econazole does not appear to offer additional benefits over monotherapy with 5% natamycin for the management of fungal keratitis.


Modulation of nitric oxide and 6-keto-prostaglandin F(1alpha) production in bovine aortic endothelial cells by conjugated linoleic acid.
Conjugated linoleic acid (CLA) refers to a group of polyunsaturated fatty acids that exist as positional (18:2) and stereo (cis/trans) isomers of conjugated dienoic octadecadienoate. Reports consistently indicate that CLA may inhibit both the onset and progression of atherosclerosis, via an as yet unknown mechanism(s). In an effort to identify the putative biochemical effects of CLA on bovine aortic endothelial cells (BAECs), the authors examined both the temporal and dose-dependent effects of a commercial CLA isomeric mixture on the expression and enzymatic function of endothelial nitric oxide synthase (eNOS) and cyclooxygenase-I/II (COX-I/II) in these cells. Initial investigations indicated that CLA mix (0 to 10 microg/mL, 0 to 24 h) failed to regulate either the expression or activity of eNOS in BAECs under basal conditions. Pretreatment of BAECs with CLA mix (10 microg/mL) for either 3 or 24 h, followed by incubation with 5 microM bradykinin (BK) for 3 h, however, increased BK-stimulated nitrite release by 2.4 +/- 0.6- and 3.0 +/- 0.4-fold, respectively, more than control cells (BK-stimulation without CLA pretreatment). Under basal conditions, CLA mix (10 microg/mL, 0 to 24 h) had no significant effect on either COX-I or COX-II expression, genes that could be readily induced in response to hemodynamic stimuli. CLA could, however, significantly attenuate BAEC release of 6-keto-prostaglandin F(1alpha) (6k-PGF(1alpha)), a stable breakdown product of prostaglandin I2 (PGI2) within the cyclooxygenase pathway, in a dose- and time-dependent manner. In conclusion, therefore, the results suggest that CLA may potentiate agonist-stimulated eNOS activation whilst attenuating COX-dependent PGI2 synthesis in BAECs. This ability to increase agonist-stimulated nitric oxide (NO) levels, whilst reducing production of inflammatory mediators within vascular ECs, supports a putative atheroprotective role for CLA and provides an important biochemical insight into its purported ability to modulate endothelium-mediated vascular homeostasis.


Point-of-care dashboards promote coproduction of healthcare services for patients with inflammatory bowel disease.
Coproduction of healthcare services by patients and professionals is seen as an increasingly important mechanism to support person-centred care delivery. Coproduction invites a deeper understanding of what persons sometimes called 'patients' bring to development of a service. Yet, little is known about tools that may help elicit that information. Our objective was to explore potential benefits and limitations of an electronic pre-visit survey (PVS) and dashboard by studying uptake and experiences within the inflammatory bowel disease (IBD) community. We conducted a mixed-method evaluation of patients and clinicians using the IBD Qorus PVS and dashboard at 24 programmes participating in the IBD Qorus learning health system. We analysed (i) descriptive statistics and thematic analyses of 537 patient surveys, (ii) semi-structured interviews with seven patients and six care teams and (iii) usage data collected between 25 March 2019 and 26 April 2020. Nearly two-thirds (64%; n = 38) of clinicians enrolled ≥25 patients into IBD Qorus; 59% (n = 29) of clinicians received ≥25 electronic PVS, with 3834 PVS received during the study period. Post-visit evaluation surveys were completed by patients following 26% (n = 993) of PVS completions. Among patients who reported using the dashboard for 1 or more months (n = 537), two-thirds (65%, n = 344) used the dashboard at a clinic visit and one-third used it outside the clinic (33%, n = 176). Most patients who used the dashboard during a clinic visit said it was helpful in discussions with their clinician (82%), in talking about what matters most (76%) and in making healthcare decisions (71%). Patients using the dashboard during the clinic visit reported higher levels of shared decision-making than those who did not use the dashboard (82% vs. 65%, P < 0.001). This relationship remained significant after controlling for receipt of care at a clinic with the highest levels of patient-reported shared decision-making (odds ratio: 2.1; confidence interval: 1.3-3.3). Patients and clinicians found the greatest value in using the PVS and dashboard to share concerns and symptoms, prepare for a visit and support discussions during the visit. The lack of integration with existing electronic health records (EHRs) limited clinician usage of the PVS and dashboard. The PVS and dashboard created a shared language, which supported coproduction and shared decision-making and facilitated a shared understanding of goals, concerns, symptoms and well-being. To support uptake, future systems should reduce implementation burden for healthcare professionals and integrate seamlessly with existing EHR systems and workflows.


Low dose systemic thrombolytic therapy for treatment of deep venous thrombosis.
Thrombolytic therapy is still not used widely for treatment of deep vein thrombosis despite its known efficacy. This reluctance to use it stems from worries about its hemorrhagic complications. In a 4-year period 97 patients with deep vein thrombosis diagnosed by duplex study were enrolled into the study. Fifty patients received streptokinase as a bolus of 250,000 units followed by 100,000 units/hr with a maximum of 4,000,000 units and 47 patients received anticoagulation with heparin. Minor hemorrhagic complications occurred in 2 patients (4%) in the thrombolytic therapy group. An improvement in the control duplex study was observed in 56% of the patients in the thrombolytic therapy group compared to 5% in the heparin group (p=0.000). The patients treated within 4 days of onset of symptoms had significantly higher success rates compared to those treated later (p=0.000). Higher success rates were obtained for those with either femoral vein or more distal venous thrombosis compared to those with iliac vein and vena cava thrombosis (p=0.007). These results show that systemic low dose streptokinase achieves significantly higher recanalization rates compared to heparin alone. Hemorrhagic complications at these dose levels are within acceptable ranges. Low dose streptokinase regimen could be beneficial in patients who present within 4 days of femoral or more distal venous thrombosis.


Spontaneous migration of cancer cells under conditions of mechanical confinement.
When cancer cells spread away from the primary tumor, they often follow the trajectories of lymphatic vessels, nerves, white matter tracts, or other heterogeneous structures in tissues. To better understand this form of guided cell migration we designed a series of microfluidic devices that mechanically constrain migrating cancer cells inside microchannels with cross-section comparable to cell size. We observed unexpectedly fast and persistent movement in one direction for several hours of cancer cells of different types. The persistent motility occurs spontaneously, in the absence of external gradients, suggesting the presence of intrinsic mechanisms driving cancer cell motility that are induced in conditions of mechanical confinement. To probe the mechanisms responsible for this behavior, we exposed cancer cells inside channels to drugs targeting the microtubules, and measured a significant reduction in the average migration speed. Surprisingly, a small number of cells appeared not to be affected by the treatment and displayed fast and persistent migration, comparable to the untreated cells. The new matrix-free, 3D-confined motility assay replicates critical interactions that cancer cells would normally have inside tissues, is compatible with high-content, high-throughput analysis of cellular motility at single cell level, and could provide useful insights into the biology of cancer cell migratory phenotype.


Validity and reliability of the Health Literacy Assessment Scale for adherence to drug treatment among diabetics.
To prepare an instrument to evaluate health literacy with regard to adherence to drug treatment among diabetics, identify the validity of its content, and estimate its reliability. Pilot study, with the following stages of instrument construction: literature review, content validation, reliability estimation (internal consistency/Cronbach's alpha and reproducibility/Kappa). The validity of content was completed and presented alpha=0.77 and Kappa values ranged from 0.31 to 1.00. The instrument was approved regarding content validity, presented acceptable internal consistency and reproducibility. However, when applied, measurement errors it can produce must be considered.


All-dielectric multifunctional transmittance-tunable metasurfaces based on guided-mode resonance and ENZ effect.
Electrically tunable metasurfaces open new doors for manipulating the phase, amplitude and polarization of light in ultrathin layers. Compared with metal assisted metasurfaces, all-dielectric transmission metasurfaces-with outstanding feature of low loss, especially incorporating with new electro-optical materials-show great potential for the next generation flat optics. In this study, by combining the epsilon-near-zero effect in indium tin oxide (ITO) with guided-mode resonance, we propose novel electrically tunable all-dielectric metasurface architectures with versatile functions for widespread potential application. The inserted periodic ITO and hafnium oxide layers sandwiched in silicon act as two metal-oxide-semiconductor capacitors in a single period to disturb the resonance wavelength in the near-infrared spectral range under the voltage applied. For the one-dimensional structure, the transmittances of this metasurface at 1512 and 1510 nm change 20 and -14 dB under 0∼5 V bias voltage, respectively. In addition, the bilayer structure performs well in double-waveband applications, indicating that more layers can support more operation wavebands. Meanwhile, the two-dimensional structure works as a polarization insensitive device when setting the same structural parameters in both orthogonal directions. The proposed architecture, with various merits including ultra-compact size, high-speed and complementary metal-oxide-semiconductor compatibility, provides a multifunctional and multi-degree-of-freedom design, as well as enormous potential applications in more complicated flat optics.


Validity and reliability of the Norwegian version of the Ferrans and Powers Quality of Life Index.
The purpose of this study was to examine the validity and reliability of the Norwegian version of the Ferrans and Powers Quality of Life Index in a sample of 131 men and women with newly diagnosed cancer. The Quality of Life Index was translated into Norwegian using a standardized international approach, including back-translation. The findings showed high internal consistency reliability for the global score (alpha = 0.93 (test)) as well as for the following domains: health and functioning (alpha = 0.88), socio-economic (alpha = 0.82), psychological/spiritual (alpha = 0.82) and family (alpha = 0.79). The test-retest reliability after 3-4 weeks was 0.78 for the global score. A factor analysis partially confirmed the different subscales. In conclusion, the Quality of Life Index was found to be reliable and had sufficient validity to be used for measuring quality of life in Norwegian cancer patients.


Evaluation of stress patterns in bone around dental implant for different abutment angulations under axial and oblique loading: A finite element analysis.
The replacement of missing anterior teeth presents peculiar challenges to the Prosthodontist. Implants are increasingly gaining favour for the same. The morphology of existing bone in the premaxilla often dictates that implants are placed at angles that are difficult to restore with conventional abutments. However, the angulated abutments might transfer unfavourable forces to the implant or bone, thereby compromising the prognosis of the treatment. Because, it is difficult to assess the generated forces clinically, a finite element analysis was chosen for the present study as it is useful tool in estimating stress distribution in the contact area of the implant with the bone. In this study, the frontal region of the maxilla was modelled with a cortical layer 1.5 mm thick containing an inner cancellous core. The implant was cylindrical, round ended, with length 13 mm and diameter 4.1 mm. The abutment was modelled as 7 mm in height with a 5 degree occlusal taper. The different abutment angulations used were 0°, 10°, 15° and 20°. The amount of loads used were 100, 125, 150, 175 and 200 N axially, and 50 N in oblique direction, to approximate the kind of loads seen in clinical situations. It was seen that, as the abutment angulation changes from 0° to 20° both the compressive as well as tensile stresses increased; but, it is within the tolerance limit of the bone. It seems reasonably safe to use angled abutments in anterior implant supported prostheses, in the maxillary arch.


Chlamydia trachomatis infection among pregnant women: prevalence and prenatal importance.
Chlamydia trachomatis infection in pregnant women is suspected to result in low birth-weight and premature infants. We conducted studies to ascertain the prevalence of this infection among pregnant women in our setting and whether its presence is a risk factor for low birth-weight or prematurity. In the first study, 94 pregnant women between 26 and 30 weeks of gestation were screened for infection with Chlamydia trachomatis. The second investigated a cohort of 172 pregnant women presenting in spontaneous labour. The infection status was related to perinatal outcome in terms of birth-weight and gestation. In both the studies, Chlamydia trachomatis infection was diagnosed using the Chlamydiazyme test performed on endocervical swabs. The prevalence of Chlamydia trachomatis infection in mid-pregnancy and at labour was 17% (16/94) and 18.6% (32/172), respectively. Women with infection were relatively older than those without it [mean (SD) age: 26.6 (4.5) years v. 24.8 (3.6) years, p = 0.01]. The mean (SD) birth-weight [2869 (611) g v. 2814 (496) g], gestation [38.5 (2.6) weeks v. 38.3 (2.0) weeks], and incidence of low birth-weight [18.7% v. 20.7%] as well as prematurity [9.4% v. 10.7%] were similar among neonates born to women with or without infection. Neonates born to infected mothers experienced purulent conjunctivitis more frequently than those born to non-infected mothers [12.5% v. 2.8%, p = 0.04]. Chlamydia trachomatis is a relatively common infection in pregnant women. However, it was not associated with either low birth-weight or prematurity.


Tungsten carbide and LMPA electron cutouts: comparison and validation using Monte Carlo modelling and measurement of dose.
Electron applicator cutouts for radiation therapy electron beam shaping are typically cast from Low Melting Point Alloys (LMPA), such as cerrobend. In this work, we describe the Monte Carlo modelling of novel 3D printed cutouts based on tungsten carbide powder and the resulting dose profiles subject to Elekta Agility electron beams. Cerrobend cutouts were also modelled using the Monte Carlo code EGSnrc. Cerrobend and tungsten carbide cutouts were found to have the same dose profiles within model variance. Computed profiles and percentage depth dose (PDDs) curves of the Elekta Agility accelerator model using standard cutouts in water were found to agree with water tank measurements using gamma criteria of 2%/2mm. The Monte Carlo computed dose profiles of the tungsten carbide cutouts in a polystyrene phantom were also found to agree with liquid-filled ionization chamber array measurements using gamma criteria of 2%/2mm. We conclude that the tungsten carbide cutouts are clinically equivalent to LMPA cutouts.


Analysis of microsatellite instability and hypermutation of immunoglobulin variable genes in Werner syndrome.
Werner syndrome (WS) is a human premature aging syndrome, which is associated with high frequencies of neoplasia and genetic instability. We have examined the occurrence of microsatellite instability, which may result from defective mismatch repair, in lymphoblastoid cell lines derived from nine WS patients. Instability was measured at the D2S123 locus by gel analysis of PCR products. Three WS cell lines had 4-13% altered alleles, compared with 0% in the other six lines. The increased frequency of microsatellite instability could not readily be associated with overt cancer or any other known clinical condition in the three patients. To examine whether the WS defect affected the humoral immune system, we measured the hypermutation of immunoglobulin variable genes in peripheral blood cells from the WS patient who donated the cell line with the highest frequency of microsatellite instability. The frequency and pattern of mutation was similar to that from normal individuals, suggesting that the Werner protein is not involved in generating hypermutation.


Effect of hypertonic saline resuscitation on heme oxygenase-1 mRNA expression and apoptosis of the intestinal mucosa in a rat model of hemorrhagic shock.
Massive blood loss due to trauma is the leading cause of death in trauma patients and military combatants. The fluid category of resuscitation for hypotensive trauma patients is open to debate. This study was conducted to investigate the early effects of hypertonic and isotonic saline solutions on heme oxygenase-1 (HO-1) mRNA expression and apoptosis in the intestinal mucosa of rats with hemorrhagic shock. A model of severe hemorrhagic shock was established in 21 Sprague-Dawley rats. The rats were randomly divided into sham, normal saline resuscitation (NS), and hypertonic saline resuscitation (HTS) groups, with 7 in each group. We assessed and compared the HO-1 mRNA expression and apoptosis in the small intestinal mucosa of rats after hemorrhagic shock and resuscitation using the SYBR Green I fluorescence quantitative reverse transcriptase polymerase chain reaction, fluorescein-iso-thiocyanate-annexin V/propidium iodide double staining, and flow cytometry. In the early stage of hemorrhagic shock and resuscitation, marked apoptosis occurred in the small intestinal mucosa from both the NS and HTS groups. The apoptotic rate in the NS group was higher than that in the HTS group (P < 0.01). Among the three groups, HO-1 mRNA mucosa from the HTS group had the highest level of expression; however, the differences were not significant. There was a significant negative correlation between HO-1 mRNA expression and apoptosis in the small intestinal mucosa from the NS and HTS groups after hemorrhagic shock and resuscitation. In this rat model of severe hemorrhagic shock, HTS resuscitation with a small volume is more effective than NS resuscitation in reducing apoptosis of the intestinal mucosa. Further, HO-1 mRNA over-expression in the intestinal mucosa may be one of the molecular mechanisms of HTS in the resuscitation of hemorrhagic shock.


Evidence of Destabilization of the Human Thymidylate Synthase (hTS) Dimeric Structure Induced by the Interface Mutation Q62R.
In human cells, thymidylate synthase (TS) provides the only source of 2'-deoxythymidyne-5'-monophosphate (dTMP), which is required for DNA biosynthesis. Because of its pivotal role, human TS (hTS) represents a validated target for anticancer chemotherapy. Nonetheless, the efficacy of drugs blocking the hTS active site has limitations due to the onset of resistance in cancer cells, requiring the identification of new strategies to effectively inhibit this enzyme. Human TS works as an obligate homodimer, making the inter-subunit interface an attractive targetable area. Here, we report the design and investigation of a new hTS variant, in which Gln62, located at the dimer interface, has been replaced by arginine in order to destabilize the enzyme quaternary assembly. The hTS Q62R variant has been characterized though kinetic assay, thermal denaturation analysis and X-ray crystallography. Our results provide evidence that hTS Q62R has a reduced melting temperature. The effective destabilization of the TS quaternary structure is also confirmed by structural analysis, showing that the introduced mutation induces a slight aperture of the hTS dimer. The generation of hTS variants having a more accessible interface area can facilitate the screening of interface-targeting molecules, providing key information for the rational design of innovative hTS interface inhibitors.


[Angiogenesis promoting effects of Chinese herbal medicine for activating blood circulation to remove stasis on chick embryo chorio-allantoic membrane].
To observe the angiogenesis promoting effects of clinical common used Chinese herbal medicines (CHM) for activating blood circulation to remove stasis on chick embryo chorio-allantoic membrane (CAM). Chicken CAM model was established and mice blood serum containing different kinds of medicines, including Radix Peaoniae rubra, Radix Angelicae sinensis, Flos Carthami, Rhizoma Chuanxiong, Radix Salviae miltiorrhizae, Astragalus membranaceus, and their complex prescriptions, Danggui Buxue Decoction, Xuefu Zhuyu Decoction, Xiongshao Capsule, was applied on it respectively to observe the condition of angiogenesis 72 hrs after incubation. Besides, the normal saline group, blank serum group, blank group and basic fibroblast growth factor (bFGF) group were set up for control. All the CHM applied and bFGF had the CAM angiogenetic promoting effect, among them, Radix Salviae Miltiorrhizae and the three complex prescriptions showed better effects than the three negative control groups in capillary formation and count, with the efficacy similar to that of bFGF. The effect of complex prescriptions was superior to that of single herb except Radix Salviae miltiorrhizae. Radix Salviae miltiorrhizae, Danggui Buxue Decoction, Xuefu Zhuyu Decoction and Xiongshao Capsule have good angiogenesis promoting effect on CAM. This study elucidated, from a certain aspect, the mechanism of action of CHM on ischemic diseases, and unfolded the scientific evidence of applying complex prescription.


Yucasin DF, a potent and persistent inhibitor of auxin biosynthesis in plants.
The plant hormone auxin plays a crucial role in plant growth and development. Indole-3-acetic acid (IAA), a natural auxin, is mainly biosynthesized by two sequential enzyme reactions catalyzed by TAA1 and YUCCA (YUC). TAA1 is involved in the conversion of tryptophan to IPA, and YUC catalyzes the conversion of IPA to IAA. We previously demonstrated that yucasin inhibits AtYUC1 enzyme activity and suppress high-auxin phenotype of YUC overexpression plants, although yucasin displayed weak effects on the auxin-related phenotype of wild-type plants. To develop more potent YUC inhibitors, various derivatives of yucasin were synthesized, and their structure-activity relationships were investigated. Yucasin difluorinated analog (YDF) (5-[2,6-difluorophenyl]-2,4-dihydro-[1,2,4]-triazole-3-thione) was identified to be a more potent YUC inhibitor than the original yucasin. YDF caused an auxin-deficient phenotype in Arabidopsis wild-type plants that was restored with auxin application. YDF was found to be highly stable regarding metabolic conversion in vivo, accounting for the potent activity of the inhibition of IAA biosynthesis in planta. Photoaffinity labeling experiments demonstrated that yucasin-type inhibitors bind to the active site of AtYUC1. YDF is a promising auxin biosynthesis inhibitor and is a useful chemical tool for plant biology and agrochemical studies.