Requirement for G protein activity at a specific time during embryonic chick myogenesis.
Signaling between embryonic myoblasts involves prostaglandin metabolism, the activation of a membrane receptor and changes in polyphosphatidyl inositol metabolism. Many of these membrane-localized events occur between 33 to 35 h of differentiation, concomitant with a dramatic change in membrane organization, in myoblast aggregates in culture. Since many receptors affect inositol phosphate metabolism by activating a GTP-binding protein (G protein), we asked if there was evidence for such a protein in myogenic signaling. We show that during the period of differentiation in culture when prostaglandin is needed to bind to a transient receptor, a pertussis toxin-sensitive but cholera toxin-insensitive G protein must act. If this activation is blocked, the characteristic change in myoblast cell adhesion and subsequent membrane fusion do not occur. We suggest that a G protein couples the activated prostaglandin receptor and the change in polyphosphatidyl inositol metabolism and that this membrane transduction step is necessary for subsequent membrane differentiation events during myogenesis.


Methanolic extract of Potentilla fulgens root and its ethyl-acetate fraction delays the process of carcinogenesis in mice.
People of north-eastern states of India consume raw areca-nut (RAN) and lime which could lead to oral, esophageal and gastric cancers. However, the incidence of these cancers are significantly lesser in those who consume pieces of Potentilla fulgens root along with RAN. Since evaluation of anticancer role, if any, of P. fulgens on RAN-mediated genetic alterations in human is difficult because of other compounding factors, this study was undertaken in mice to focus on gastric carcinogenesis since ad libitum administration of RAN extract with lime in drinking water induced stomach cancer due to greater exposure of its lining. A total of 160 mice were used at different time points and either methanol extract of P. fulgens roots (PRE) or mixture of four compounds of ethyl-acetate fraction (EA-mixture) was mixed with mice feed. Histological studies revealed that RAN + lime induced cancer in all the mice and interestingly only 20% developed cancer when PRE/EA-mixture was provided along with RAN + lime. Higher frequency of precocious anaphase and over expression of p53 and Securin genes were significantly reduced by PRE/EA-mixture. Thus PRE/EA-mixture mitigates the RAN-induced tumor-initiating process in stomach by maintaining expression of tumor suppressor and check-point genes under control.


A molecular mechanism for therapeutic effects of cGMP-elevating agents in pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a progressive, usually fatal disease with abnormal vascular remodeling. Pulmonary artery smooth muscle cells (PASMCs) from PAH patients are hyperproliferative and apoptosis-resistant and demonstrate decreased signaling in response to bone morphogenetic proteins (BMPs). Cyclic GMP-elevating agents are beneficial in PAH, but their mechanism(s) of action are incompletely understood. Here we show that BMP signaling via Smad1/5/8 requires cGMP-dependent protein kinase isotype I (PKGI) to maintain PASMCs in a differentiated, low proliferative state. BMP cooperation with cGMP/PKGI was crucial for transcription of contractile genes and suppression of pro-proliferative and anti-apoptotic genes. Lungs from mice with low or absent PKGI (Prkg1(+/-) and Prkg1(-/-) mice) exhibited impaired BMP signaling, decreased contractile gene expression, and abnormal vascular remodeling. Conversely, cGMP stimulation of PKGI restored defective BMP signaling in rats with hypoxia-induced PAH, consistent with cGMP-elevating agents reversing vascular remodeling in this PAH model. Our results provide a mechanism for the therapeutic effects of cGMP-elevating agents in PAH and suggest that combining them with BMP mimetics may provide a novel, disease-modifying approach to PAH therapy.


The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-Shigella spp.
Shigella bacteria cause shigellosis, a gastrointestinal infection most often acquired from contaminated food or water. In this review, the general characteristics of Shigella bacteria are described, cases of laboratory-acquired infections (LAIs) are discussed, and evidence gaps in current biosafety practices are identified. LAIs are undoubtedly under-reported. Owing to the low infectious dose, rigorous biosafety level 2 practices are required to prevent LAIs resulting from sample manipulation or contact with infected surfaces. It is recommended that, before laboratory work with Shigella, an evidence-based risk assessment be conducted. Particular emphasis should be placed on personal protective equipment, handwashing, and containment practices for procedures that generate aerosols or droplets.


Conformational and vibrational studies of isomeric hydrogen cyanide tetramers by quantum chemical methods.
The results of structural studies and detailed harmonic and anharmonic vibrational analysis on two hydrogen cyanide (HCN) tetramers diaminomaleonitrile (DAMN) and diaminofumaronitrile (DAFN), which are important molecules for understanding the chemistry of interstellar space and nitrile rich environments, are being reported on the basis of density functional theory using second-order perturbation theory. Both the molecules are found to have C1 symmetry. While all the heavy atoms of DAMN lie in the same plane (maximum deviation 6°), the two nitrogen atoms in DAFN are out of plane by about 15°. The two amino groups are tetrahedral and do not have significant bond angle anisotropy. Detailed conformational studies are reported on the two molecules and their possible rotational isomers are identified. Complete vibrational analysis based on harmonic and anharmonic frequencies, intensity of infrared and activity of Raman bands and potential energy distribution over the internal coordinates has been provided for the two molecules. Affect of hydrogen bonding on molecular geometry and frequencies of the NH stretch modes has been studied by calculations on the dimers of the two molecules. A close agreement has been observed between the experimental and calculated frequencies. Vibrational-rotational constants such as rotational constants in the ground vibrational state (A0, B0, C0) and the effective rotational constants (Ae, Be and Ce), including terms due to quartic centrifugal distortion constants, rotation-vibration coupling constants, Wilson and Nielsen's centrifugal distortion constants have been calculated using B3LYP and B97-1 functionals and 6-31G**, 6-311+G** and TZVP basis sets.


Development and pharmacist-mediated use of tools for monitoring atypical antipsychotic-induced side effects related to blood glucose levels.
Drug side effects often lead to serious outcomes. Administration of second-generation antipsychotics has resulted in diabetic ketoacidosis and diabetic coma leading to death. Therefore, pharmacists are required to collect information on clinical test values, determine the appropriate test timing, and coordinate with doctors for further clinical laboratory orders, all of which are labor-intensive and time-intensive tasks. In this study, we developed a side effect-monitoring tool and aimed to clarify the influence and efficiency of monitoring side effects by using the tool in patients taking atypical antipsychotics in whom it is necessary to check clinical test values such as blood sugar levels. We extracted clinical test values for patients treated with second-generation antipsychotics from electronic medical records. The test values are automatically displayed in the side effect grade classification specified by CTCAE ver. 4.0. A database was constructed using scripts to provide alerts for the timing of clinical testing. The pharmacist used this tool to confirm clinical test values for patients taking medication and requested the physician to inspect orders based on the appropriate test timings. The management tool reduced the pharmacists' effort in collecting information on patients' prescription status and test values. It enabled patients to undergo tests at the appropriate time according to the progression of glucose metabolism and allowed for easy monitoring of side effects. The results suggested that regardless of pharmacists' experience or skill, the introduction of this tool enables centralization of side effect monitoring and can contribute to proper drug use.


Model services for treatment/management of the mentally retarded-mentally ill.
Mental illness affects nearly 25-30% of America's mentally retarded population. While a small number of these individuals will require institutional care, it is clearly possible to serve the majority in community-based residential settings. This paper will provide an overview of the various types of mental illness found in the mentally retarded population currently served by the Eastern Nebraska Community Office of Retardation (ENCOR), examine the treatment challenges which the provision of services to this special population have presented, and share recommendations as to how the ENCOR model can assist other communities in serving similar complex subpopulations in a developmental and cost-efficient manner.


Perspectives on Mental Illness Stigma Among African Immigrant Pregnant and Post-Partum Women in an Urban Setting: A Brief Report.
This study assessed the perspectives of pregnant and postpartum African immigrant women on mental illness. We conducted a focus group session (n=14) among pregnant and postpartum African immigrant women in June 2020. We used an inductive driven thematic analysis to identify themes related to mental health stigma. Five core themes emerged: conceptualization of mental health, community stigmatizing attitudes, biopsychosocial stressors, management of mental health, and methods to reduce stigma. Understanding the perspectives of pregnant African immigrant women at the intersection of their race, ethnicity, gender, and migration are necessary to improve engagement with mental health services.


Lipolytic enzymes of the digestive organs of the crown-of-thorns starfish (Acanthaster planci): comparison of the stomach and pyloric caeca.
1. Stomach and pyloric caeca homogenates from the crown-of-thorns starfish hydrolysed p-nitrophenyl esters, alpha-naphthyl esters, cholesteryl oleate and tributyrin. The pyloric caeca contained the highest activities. 2. The p-nitrophenyl acetate hydrolytic activity eluted at 0.23 M NaCl on ion exchange chromatography while the p-nitrophenyl palmitate hydrolytic activity eluted between 0.2 and 1.0 M NaCl. 3. Polyacrylamide gel zymograms for alpha-naphthyl acetate hydrolytic activity revealed one major band and several minor bands of activity for both tissues. 4. Isoelectric focusing zymograms revealed one major band with a pI = 4.2 for both tissues, with an additional band at pI = 3.5 for pyloric caeca. 5. The pyloric caeca contained twice as much lipid as the stomach. Lipid extracts contained mixtures of steroids and steroid-esters; a cholesterol-like sterol was tentatively identified.


Influence of ventilatory and circulatory changes on the pharmacokinetics of halothane and isoflurane.
In two groups of dogs, uptake and elimination of halothane and isoflurane were studied using a closed-loop anesthesia system which automatically controlled end-tidal halothane or isoflurane partial pressure at minimal alveolar concentration (MAC) equivalent levels. Hemodynamic and respiratory variables were recorded and the anesthetic partial pressure was measured in the inspired and expired air, as well as in the arterial, cerebrovenous and mixed venous blood. Data were recorded during wash-in, hyperventilation, hypercirculation, hypotension and wash-out. For halothane, the controller delivered a higher inspired partial pressure than for isoflurane to compensate for the higher blood/gas partition coefficient. This was especially pronounced during the wash-in and the hypercirculation periods. Smaller differences between halothane and isoflurane partial pressures occurred during hyperventilation, hypotension and the wash-out period and could be explained by the lower solubility of isoflurane. These results show that even under unstable ventilatory and hemodynamic conditions, the inspired concentration of isoflurane has to be adjusted less often and to a smaller degree than that of halothane if end-tidal concentrations are to be maintained constant.


Noradrenergic innervation of the penis in control and streptozotocin-diabetic rats: evidence of autonomic neuropathy.
The noradrenergic sympathetic innervation of the penis of control and 4-month streptozotocin-diabetic rats was examined with the glyoxylic acid histofluorescence method. Noradrenergic varicosities were found in the corpora cavernosa in a dense subtunical plexus and in the perisinusoidal and trabecular regions of the erectile tissue, in the corpus spongiosum in perisinusoidal tissue, around large arteries and veins, and around small tortuous arterioles and small draining veins of the corpora cavernosa and spongiosum. Noradrenergic varicosities were diminished in number and fluorescent intensity in all regions of the penis of diabetic rats compared with controls. The subtunical plexus was absent, perisinusoidal and trabecular varicosities were sparse, and only occasional intermittent, discontinuous, dull fluorescent fibers or plexuses were found around the vessels. Quantitation with high-performance liquid chromatography revealed a significant reduction of norepinephrine in the penis of diabetic rats compared with controls. The present study suggests that long-term streptozotocin diabetes in the rat is accompanied by sympathetic autonomic neuropathy of the penis that seems to parallel changes in the noradrenergic content of penile corpora of men with diabetes and erectile impotence. The streptozotocin-diabetic rat merits further study to explore the relationship between noradrenergic innervation of the penis and erectile tissue.


One sensor acoustic emission localization in plates.
Acoustic emissions are elastic waves accompanying damage processes and are therefore used for monitoring the health state of structures. Most of the traditional acoustic emission techniques use a trilateration approach requiring at least three sensors on a 2D domain in order to localize sources of acoustic emission events. In this paper, we present a new approach which requires only a single sensor to identify and localize the source of acoustic emissions in a finite plate. The method proposed makes use of the time reversal principle and the dispersive nature of the flexural wave mode in a suitable frequency band. The signal shape of the transverse velocity response contains information about the propagated paths of the incoming elastic waves. This information is made accessible by a numerical time reversal simulation. The effect of dispersion is reversed and the original shape of the flexural wave is restored at the origin of the acoustic emission. The time reversal process is analyzed first for an infinite Mindlin plate, then by a 3D FEM simulation which in combination results in a novel acoustic emission localization process. The process is experimentally verified for different aluminum plates for artificially generated acoustic emissions (Hsu-Nielsen source). Good and reliable localization was achieved for a homogeneous quadratic aluminum plate with only one measurement.


Lithium carbonate increases marrow granulocyte-committed colony-forming units and peripheral blood granulocytes in a canine model.
Psychiatric patients given lithium carbonate (LC) commonly develop granulocytosis of the peripheral blood. This is an important observation with several potential applications in clinical hematology and oncology. In order to study further this phenomenon, we have developed an animal model of LC-induced granulocytosis. Four mongrel dogs weighing 23--28 kg were given commercially available LC in 300 mg capsules by mouth twice daily. Peripheral blood was examined twice weekly and marrow granylocyte-committed colony forming units (CFU-c) were studied weekly. Significant increments of peripheral granulocytes (P = 0.003) and of marrow CFU-c (P =0.001) were noted. An increased number of marrow CFU-c has not been previously reported but is consistent with other knowledge about this phenomenon. We conclude that this convenient animal model may be of value in further studies of LC-induced granulocytosis and its possible applications.


Nitrogen removal by the enhanced floating treatment wetlands from the secondary effluent.
Three novel floating treatment wetlands, including autotrophic enhanced floating treatment wetland (AEFTW), heterotrophic enhanced floating treatment wetland (HEFTW) and enhanced floating treatment wetland (EFTW) were developed to remove nitrogen from the secondary effluent. Results showed that the analogously excellent nitrogen removal performance was achieved in AEFTW and HEFTW. About 89.4% of the total nitrogen (TN) was removed from AEFTW at a low S/N of 0.9 and 88.5% from HEFTW at a low C/N of 3.5 when the hydraulic retention time (HRT) was 1d in summer. Higher nitrification and denitrification performance were achieved in AEFTW. Addition of electron donors effectively reduced the N2O emission, especially in summer and autumn. High-throughput sequencing analysis revealed that the electron donors distinctly induced the microbial shifts. Dechloromonas, Thiobacillus and Nitrospira became the most predominant genus in HEFTW, AEFTW and EFTW. And autotrophic and heterotrophic denitrification could simultaneously occur in HEFTW and AEFTW.


Simultaneous quantification of 50 bioactive compounds of the traditional Chinese medicine formula Gegen-Qinlian decoction using ultra-high performance liquid chromatography coupled with tandem mass spectrometry.
The quality evaluation of patent drugs derived from traditional Chinese medicine (TCM) compound formulas has been challenging due to their complex chemical composition. In this study, we developed a solution to evaluate the quality of Gegen-Qinlian Decoction (GQD), an ancient four-herb TCM formula for the treatment of diarrhea and diabetes, together with its derived patent drugs by simultaneously quantifying 50 bioactive compounds. The samples were extracted by 100% methanol (for hydrophobic compounds) and 50% methanol in water (for hydrophilic compounds), respectively, and were separated on a Waters Acquity charged surface hybrid C18 column (2.1×100mm, 1.7μm) eluted with gradients of acetonitrile and water containing 0.1% formic acid at a flow rate of 400μL/min. The analytes were determined by ultra-high performance liquid chromatography coupled with tandem mass spectrometry in the selected reaction monitoring mode. The 50 compounds (including acidic and alkaline, hydrophilic and hydrophobic) were well resolved within 14min, and were determined using an internal standard method. The method was fully validated for precision, repeatability, and recovery. The limits of detection were 0.3-10.0ng/mL. Finally, this method was used to analyze 24 batches of GQD samples, including water decoction, pills, tablets, and oral solutions. Principal component analysis indicated significantly varied chemical compositions among these formulations. The tablets and pills contained higher concentrations of Scutellaria and Coptis compounds than the oral solutions, and the water decoction contained abundant glycosides and saponins. Moreover, the contents of flavanones and flavone O-glucuronides varied remarkably. This study provides a feasible solution for the comprehensive quality control of TCM patent drugs.


A cross-sectional study of the impact of school neighbourhood on children obesity and body composition.
Schools' neighbourhoods provide an important environmental context that may influence the risk of obesity among children. The aim of this study was to assess the effect of neighbourhood surrounding schools on obesity and body composition in schoolchildren. Data on 845 children aged 7 to 12 years old from 20 primary schools were considered. Anthropometric measurements and bioelectrical impedance analysis were performed to assess body mass index (BMI) and characterize body composition. Land use characteristics were quantified within a 500-m buffer zone around schools. Mixed-effect models measured the effects of school neighbourhood on obesity and body composition. The results showed a tendency between green urban areas around schools and lower values of BMI and better body composition parameters compared with built areas, being BMI z-scores CDC, and body fat percentage significantly higher in-built than in green urban areas (β = 0.48, 95% CI 0.05; 0.90, and β = 2.56, 95% CI 0.39; 4.73, respectively).Conclusion: Our findings suggest that the school neighbourhood has an effect on BMI and body fat percentage in schoolchildren. These results may contribute to the creation of healthier cities and help reduce health expenses by focusing on prevention programmes towards the expansion of green spaces. What is Known: • Living in greener areas has been associated with healthy weight outcomes and to the lower impact of obesogenic urban environments. • The school environment may be especially important for youth health outcomes. What is New: • Neighbourhoods around schools may affect child health, specifically the development of obesity. • The presence of urban green areas around school may promote a framework of lifestyle or behaviours conducive to achieving a healthy weight.


Cervical thymic rebound after cancer treatment.
While newly recognized neck masses in children previously treated for malignancy raise the specter of recurrent disease, recent experience with 2 patients has shown us that enlargement of cervical thymic tissue should be considered in the differential diagnosis, especially early after the completion of chemotherapy or immunotherapy.


Mammalian target of rapamycin complex 1 (mTORC1) enhances bortezomib-induced death in tuberous sclerosis complex (TSC)-null cells by a c-MYC-dependent induction of the unfolded protein response.
Many factors, including duration and intensity of the unfolded protein response (UPR), dictate whether cells will adapt to endoplasmic reticulum stress or undergo apoptosis. In tuberous sclerosis (TSC), elevation of mammalian target of rapamycin complex 1 (mTORC1) activity has been proposed to compound the induction of UPR transcription factors ATF4 and CHOP, suggesting that the UPR could be targeted to eradicate TSC1/2-null cells during patient therapy. Here we report that control of c-MYC translation by mTORC1 plays a key role in determining whether TSC2-null Elt3 rat leiomyoma cells apoptose in response to UPR induction by the proteasome inhibitor bortezomib. Although bortezomib induces eukaryotic initiating factor 2α phosphorylation, mTORC1 activity was also required for downstream induction of the UPR transcription factors ATF4 and CHOP by a mechanism involving increased expression of c-MYC. Although bortezomib-induced c-MYC transcription was resistant to rapamycin treatment, mTORC1 activity was required for efficient c-MYC translation. c-MYC subsequently bound to the ATF4 promoter, suggesting direct involvement of an mTORC1/c-MYC-driven signaling pathway in the activation of the UPR. Consistent with this notion, exogenously expressed c-MYC reversed the ability of rapamycin to prevent bortezomib-induced CHOP and ATF4 expression as well as apoptosis. These findings indicate that the induction of ATF4/CHOP expression occurs via mTORC1 regulation of c-MYC and that this signaling pathway is a major determinant in the ability of bortezomib to induce apoptosis.


Cigar smoking prevalence and morbidity among US adults, 2000-2015.
Cigar smoking causes many of the same health conditions as cigarettes, but less information is available on prevalence of use trends and the disease burden of cigar smoking in the US. To examine these issues, we analyzed cigar use and health condition data from the National Health Interview Survey from 2000, 2005, 2010, and 2015, estimating prevalence of use by year and over time. We also estimated the number of, and adjusted disease prevalence ratios for, US adults aged ≥35 years with self-reported history of heart disease, stroke, or cancer attributable to cigar smoking. We found that prevalence of current cigar smoking has remained generally stable at around 2.3% among US adults aged ≥18 years between 2000 and 2015 but has increased among female and non-Hispanic black adults. Former exclusive cigar smokers were more likely to report having had heart conditions (aPR = 1.33, 95% CI = 1.03-1.72), stroke (aPR = 2.42, 95% CI = 1.57-3.75), and cancer (aPR = 1.44, 95% CI = 1.09-1.88) than never cigar smokers. It is estimated that nearly 200,000 cardiovascular conditions and cancer cases among US adults are attributable to former exclusive cigar smoking. This analysis shows that prevalence of current cigar smoking has remained stable among US adults but has increased among certain demographic groups. Former exclusive cigar use is associated with increased prevalence of heart disease, stroke, and cancer, which may result in part from smoking cessation following disease onset.


Spatiotemporal and cell-state control of antigen presentation during tolerance and immunity.
Effective adaptive immunity is rendered possible by highly organized tissue architecture and coordinated cellular crosstalk. While detailed spatiotemporal analyses of antigen presentation and adaptive immune activation in secondary lymphoid tissues have been a major focus of study, it is clear that antigen presentation in other tissues also plays a critical role in shaping the immune response. In this article, we concentrate on two opposing aspects of adaptive immunity: tolerance and antitumor immunity, to illustrate how a complex set of antigen presentation mechanisms contributes to maintaining a delicate balance between robust immunity and avoidance of autoimmune pathology. We emphasize the importance of how immune cell identity, state, and location collectively determine the nature of adaptive immune responses.


Application of mizoribine after keratoplasty and in the treatment of uveitis.
Mizoribine, an immunosuppressive agent developed and marketed in Japan, was tested in experimental keratoplasty and in Behçet's disease. The drug, 2 to 4 mg/kg of body weight, administered systemically or as 10% eyedrops five times daily, suppressed immune reaction after keratoplasty in rabbits. It seemed effective in 18 cases including 12 regrafted eyes. In 29 cases of Behçet's disease, the average recurrence rate dropped from once per month to once every three months in one year. Mizoribine is safe, easy to use, and may be of some value by itself or in combination with other drugs in the treatment of uveitis and in the prevention of corneal graft reaction.


Sorptive removal of disinfection by-product precursors from UK lowland surface waters: Impact of molecular weight and bromide.
The current study compared the impact of three different unit processes, coagulation, granular activated carbon (GAC), and a novel suspended ion exchange (SIX) technology, on disinfection by-product formation potential (DBPFP) from two UK lowland water sources with medium to high bromide content. Specific attention was given to the influence of the organic molecular weight (MW) fraction on DBPFP as well as the impact of bromide concentration. Whilst few studies have investigated the impact of MW fractions from Liquid Chromatography with Organic Carbon Detection (LC-OCD) analysis on dissolved organic carbon (DOC) removal by different processes, none have studied the influence of DOC MW fractions from this analysis on DBP formation. The impact of higher bromide concentration was to decrease the total trihalomethane (THM) and haloacetic acid (HAA) mass concentration, in contrast to previously reported studies. Results indicated that for a moderate bromide concentration source (135 μg/L), the THM formation potential was reduced by 22% or 64% after coagulation or SIX treatment, respectively. For a high bromide content source (210 μg/L), the THM formation potential removal was 47% or 69% following GAC or SIX treatment, respectively. The trend was the same for HAAs, albeit with greater differences between the two processes/feedwaters with reference to overall removal. A statistical analysis indicated that organic matter of MW > 350 g/mol had a significant impact on DBPFP. A multiple linear regression of the MW fractions against DBPFP showed a strong correlation (R2 between 0.90 and 0.93), indicating that LC-OCD analysis alone could be used to predict DBP formation with reasonable accuracy, and offering the potential for rapid risk assessment of water sources.


Random Phase Approximation Applied to Many-Body Noncovalent Systems.
The random phase approximation (RPA) has received considerable interest in the field of modeling systems where noncovalent interactions are important. Its advantages over widely used density functional theory (DFT) approximations are the exact treatment of exchange and the description of long-range correlation. In this work, we address two open questions related to RPA. First, we demonstrate how accurately RPA describes nonadditive interactions encountered in many-body expansion of a binding energy. We consider three-body nonadditive energies in molecular and atomic clusters. Second, we address how the accuracy of RPA depends on input provided by different DFT models, without resorting to self-consistent RPA procedure, which is currently impractical for calculations employing periodic boundary conditions. We find that RPA based on the SCAN0 and PBE0 models, that is, hybrid DFT, achieves an overall accuracy between CCSD and MP3 on a data set of molecular trimers from Řezáč et al. ( J. Chem. Theory. Comput. 2015 , 11 , 3065 ). Finally, many-body expansion for molecular clusters and solids often leads to a large number of small contributions that need to be calculated with high precision. We therefore present a cubic-scaling (or self-consistent field (SCF)-like) implementation of RPA in atomic basis set, which is designed for calculations with high numerical precision.


Interest of para-aortic lymphadenectomy for locally advanced cervical cancer in the era of PET scanning.
Treatment of locally advanced cervical cancer (LACC) involves pelvic chemoradiotherapy, using an extended field in the case of para-aortic involvement. 18-Fluoro-D-glucose positron emission tomography combined with computer tomography (PET-CT) is an accurate method for the detection of metastatic nodes. The objective of this study was to evaluate the performance of PET-CT for lymph node staging of LACC. This bicentric retrospective study included patients with LACC who had a PET-CT scan followed by para-aortic lymphadenectomy between January 2015 and December 2019. Based on pathological findings, sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and false-negative (FN) rates of PET-CT for para-aortic node involvement were evaluated. Seventy-one patients who had undergone laparoscopic lymphadenectomy were included in this study. The intraoperative complication rate was 2.8%. Sensitivity, specificity, NPV and PPV for PET-CT were 55% [95% confidence interval (CI) 44.6-67.1], 84% (95% CI 75-92), 93% (95% CI 87-99) and 33% (95% CI 22-44), respectively. FN rates in the case of negative or positive pelvic PET-CT were 5.7% and 9.5%, respectively. Para-aortic lymphadenectomy is recommended for lymph node staging in the case of negative para-aortic PET-CT. In view of the low FN rate of PET-CT, surgical staging should be discussed regardless of pelvic status if the patient presents high surgical risk, or if this delays the commencement of chemoradiotherapy.


Avian peritoneal exudate cells: a comparison of stimulation protocols.
The influence of different stimulation protocols on the induction of peritoneal exudate cells (PECs) and adherent cells, and on the percentage of different adherent cell types was examined in the chicken and Japanese quail. The results suggest that different protocols may be selected to maximize isolation of specific PEC populations for immunological studies. In the chicken, starch, peptone, glycogen, and Sephadex G-40 were all equally effective and superior to saline in generating PECs. While a single injection of Sephadex produced the highest yield of adherent cells with a maximum percentage of macrophages, repeated injections of Sephadex led to dramatic increases in non-adherent PECs (lymphocytes). In contrast, a single injection of starch was optimum for generating non-macrophage adherent cells (primarily heterophils). Since responses of the Japanese quail to stimulation with starch and saline were similar to those observed for the chicken, it is suggested that these protocols may be generally applicable for use with avian species.


Choline acetyltransferase. Purification procedure and factors affecting chromatographic properties and enzyme stability.
Purified choline acetyltransferase had a specific activity of 142 mumol of acetylcholine produced min-1 mg-1 and consisted of two proteic forms with Mr = 72,000 and 76,000 on sodium dodecyl sulfate gel electrophoresis. The separation of more than one peak of enzyme activity on CM-cellulose chromatography was shown to reflect the interaction of choline acetyltransferase with other proteins rather than the resolution of different isoenzymes. Purified choline acetyltransferase exhibited a high degree of stability. Enzyme stability was greatly dependent upon the procedures used to reach a given degree of purity, rather than the degree of purity per se, suggesting that specific proteins may be involved in the mechanism of enzyme inactivation. Use of affinity chromatography over Sepharose-blue dextran early in the preparation produced enzyme which was unstable both to storage and to concentration. Although the addition of other proteins such as bovine serum albumin had no significant stabilizing effect, the presence of acetyl coenzyme A during concentration prevented inhibition. Finally, it was shown that the purified enzyme is representative of the total enzyme present in brain in terms of both specific activity and immunochemical properties.


[Orbital bone infarction in a child with homozygous sickle cell disease].
Vaso-occlusive crises are the most common complication of sickle cell disease. Orbital bone infarction is an unusual manifestation of sickling disorders. It is suspected in patients with acute painful periorbital swelling. Orbital compression syndrome with possible optic nerve injury is a rare but serious complication; therefore, this diagnosis should be considered. Orbital infarction can be difficult to distinguish from osteomyelitis or skin infections. Imaging can be helpful in differentiating infection from infarction. We report a case of orbital bone infarction in a 14-year-old boy with sickle cell disease. Under medical treatment, the clinical course resolved with no sequelae.


Decreased albumin secretion in serum-free primary cultures of adult rat hepatocytes during proliferation induced by epidermal growth factor and insulin.
Upon addition of epidermal growth factor (EGF, 0.1 microgram/ml) and insulin (0.1 microM), adult rat hepatocytes proliferated and increased 120-134% in number in serum-free primary culture. However, in the absence of the growth factors, hepatocytes decreased in number with time. The average albumin secretion per cell was much lower in the proliferating cultures than in the non-proliferating cultures. The results suggest that albumin production in hepatocytes decreases during cell proliferation.


Factors of importance in determining the prevalence of indoor molds.
The concentration of molds isolated in 68 homes of allergic patients in southern California using the Andersen volumetric sampler varied from a minimum of 36 to a maximum of 5,984 isolate/M3 air sampled. The most frequently isolated included Cladosporium, Penicillium species. Alternaria, Sterile (Non-sporulating) Mycelium, Epicoccum, Aspergillus species, Aureobasidium and Dreschlera. Statistically significant higher mold isolates were associated with high shade and high levels of organic debris near the home and poor landscaping and landscape maintenance. Low concentrations of mold isolates were associated with the presence of a central electrostatic filtration system and good compliance with dust controls. The viable mold spore levels were lower in homes where the electrostatic filtration unit was operated continuously rather than intermittently. No statistically significant correlations could be made between indoor mold isolates and any of the following: number and age of the occupants, age and size of home, month of survey or the presence of indoor plants.


Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles.
Efficient conversion of strongly absorbed light by plasmonic gold nanoparticles to heat energy and their easy bioconjugation suggest their use as selective photothermal agents in molecular cancer cell targeting. Two oral squamous carcinoma cell lines (HSC 313 and HOC 3 Clone 8) and one benign epithelial cell line (HaCaT) were incubated with anti-epithelial growth factor receptor (EGFR) antibody conjugated gold nanoparticles and then exposed to continuous visible argon ion laser at 514nm. It is found that the malignant cells require less than half the laser energy to be killed than the benign cells after incubation with anti-EGFR antibody conjugated Au nanoparticles. No photothermal destruction is observed for all types of cells in the absence of nanoparticles at four times energy required to kill the malignant cells with anti-EGFR/Au conjugates bonded. Au nanoparticles thus offer a novel class of selective photothermal agents using a CW laser at low powers. The potential of using this selective technique in molecularly targeted photothermal therapy in vivo is discussed.


The VD1/RPD2 neuronal system in the central nervous system of the pond snail Lymnaea stagnalis studied by in situ hybridization and immunocytochemistry.
VD1 and RPD2 are two giant neuropeptidergic neurons in the central nervous system (CNS) of the pond snail Lymnaea stagnalis. We wished to determine whether other central neurons in the CNS of L. stagnalis express the VD1/RPD2 gene. To this end, in situ hybridization with the cDNA probe of the VD1/RPD2 gene and immunocytochemistry with antisera specific to VD1 and RPD2 (the alpha 1-antiserum, Mab4H5 and ALMA 6) and to R15 (the alpha 1 and 16-mer antisera) were performed on alternate tissue sections. A VD1/RPD2 neuronal system comprising three classes of neurons (A1-A3) was found. All neurons of the system express the gene. Division into classes is based on immunocytochemical characteristics. Class A1 neurons (VD1 and RPD2) immunoreact with the alpha 1-antiserum, Mab4H5 and ALMA 6. Class A2 neurons (1-5 small and 1-5 medium sized neurons in the visceral and right parietal ganglion, and two clusters of small neurons and 5 medium-sized neurons in the cerebral ganglia) immunoreact with the alpha 1-antiserum and Mab4H5, but not with ALMA 6. Class A3 neurons (3-4 medium-sized neurons and a cluster of 4-5 small neurons located in the pedal ganglion) immunoreact with the alpha 1-antiserum only. All neurons of the system are immunonegative to the R15 antisera. The observations suggest that the neurons of the VD1/RPD2 system produce different sets of neuropeptides. A group of approximately 15 neurons (class B), scattered in the ganglia, immunostained with one or more of the antisera, but did not react with the cDNA probe in in situ hybridization.


Impact of a severe tick infestation at Little Rock AFB, Arkansas on volant scorpion military training.
Over 950 students attending Volant Scorpion training during March-August 1988 reported the number and impact of tick bites and the personal protective measures used during their training at Little Rock Air Force Base. In some classes, as many as 50% of the students reported 10 or more tick bites. Approximately one third of all students said that ticks had a significant or very significant impact on duty performance. The use of a repellent applied to clothing had no significant effect on the number of tick bites received.


OCC-1D regulates Wnt signaling pathway: potential role of long noncoding RNA in colorectal cancer.
Aberrant activation of the Wnt signaling pathway is observed in most colorectal cancers (CRC). OCC-1D is a splice variant of OCC-1 gene which is considered as a long noncoding RNA (lncRNA) due to lacking the translational initiation codon of the gene. Here, we sought supporting evidence for the effects of OCC-1D on the Wnt pathway and cell cycle progression in CRC. TOP/FOPflash assay and qRT-PCR indicated that expression alterations of OCC-1D could change Wnt signaling activity in colon cancer cells. Consistently, immunocytochemistry results showed the effect of OCC-1D overexpression on nuclear localization of β-catenin proteins in SW480 cells. Flow cytometry, wound healing and MTT assay confirmed the cell cycle stimulatory effects of OCC-1D in CRC-originated cell lines (SW480 and HCT116). qRT-PCR revealed a positive correlation between the expression level of OCC-1D and its neighboring gene, APPL2. Two distinct tests, downregulation of APPL2 mRNA by using shRNA and Wnt signaling inhibition by using small molecule, along with OCC-1D overexpression confirmed that OCC-1D lncRNA exerts its effect on Wnt signaling pathway through expression modulation of APPL2 gene. Collectively, we suggested the putative regulatory effects of OCC-1D lncRNA on cell cycle progression and Wnt signaling activation through enhancing the APPL2 gene transcription.


Serum RDW and MPV in Ankylosing Spondylitis: Can they show the disease activity?
To determine RDW and MPV levels in Ankylosing Spondylitis (AS) and to investigate their relations with disease activity. 133 patients with AS (male: 80, female: 53) and age-sex matched 133 controls (male: 79, female: 54) were enrolled. Demographic data, disease activity scores, Complete Blood Count (CBC), Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) levels were recorded. The mean ages of patients and controls were 41.9±11.2 and 39.7±14.2 years respectively (p = 0.16). RDW (14.5±1.6% and 13.2±0.8%, p < 0.0001 respectively) and MPV (10.1±0.8fl and 9.9±0.7fl, p = 0.03, respectively) were significantly higher in patients with AS than in controls. There was a significant difference in RDW between patients with active AS (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >4) and those with inactive AS (BASDI <4) patients (14.84±1.79fl, 14.24±1.37fl, p = 0.035 respectively). RDW was positively correlated with BASDAI (r = 0.33, P < 0.0001), ESR (r = 0.45, P < 0.0001) and CRP (r = 0.42, P < 0.0001) and PLT levels (r = 0.24, P = 0.004). While MPV was not correlated with BASDAI, it was negatively correlated with ESR (r = -0.19, P = 0.03), CPR (r = -0.26, P = 0.004) and PLT levels (r = -0.39, P = <0.0001). RDW and MPV were significantly higher in the patients with AS than in the controls. While RDW was correlated with BASDAI and APRs, MPV was only correlated with APRs.


Effects of an angiotensin II receptor antagonist and angiotensin-converting enzyme inhibitors on burst forming units-erythroid in chronic hemodialysis patients.
Angiotensin-converting enzyme (ACE) inhibitors have been reported to reduce the response to erythropoietin (EPO) administration in chronic hemodialysis patients, but the mechanism for this effect has not yet been clarified. To clarify the mechanism of ACE inhibitors- and angiotensin II type 1 (AT1) receptor antagonist-induced anemia in hemodialysis patients, we examined the effect of ACE inhibitors and AT1 receptor antagonist on burst-forming units-erythroid (BFU-E) in the peripheral blood of hemodialysis patients and healthy controls in vitro. Peripheral blood mononuclear cells (PBMNCs) were isolated by gradient centrifugation from 10 patients on regular hemodialysis and 7 healthy control volunteers. A colony assay of hematopoietic progenitors was performed using the methylcellulose culture system. PBMNCs of 1 or 2 x 10(5) were plated in a medium containing EPO with various concentrations of ACE inhibitors or AT1 receptor antagonist and incubated for 14 days. Colonies of BFU-E were counted under an inverted microscope. The PBMNCs from the chronic hemodialysis patients formed fewer BFU-Es than those from healthy volunteers. AT1 receptor antagonist in both healthy volunteers and hemodialysis patients suppressed the number of BFU-Es. The ACE inhibitors produced a smaller effect than the AT1 receptor antagonist. AT1 receptor blockade can directly inhibit erythropoiesis in vitro.


Signaling networks organizing regenerative growth of the zebrafish fin.
In contrast to mammals, adult salamanders and fish can completely regenerate their appendages after amputation. The cellular and molecular mechanisms underlying this fascinating phenomenon are beginning to emerge, including substantial progress in the identification of signals that control regenerative growth of the zebrafish caudal fin. Despite the fairly simple architecture of the fin, the regulation of its regeneration is complex. Many signals, including fibroblast growth factor (FGF), Wnt, Hedgehog (Hh), retinoic acid (RA), Notch, bone morphogenic protein (BMP), activin, and insulin-like growth factor (IGF), are required for regeneration. Much work needs to be done to dissect tissue-specific functions of these pathways and how they interact, but Wnt/β-catenin signaling is already emerging as a central player. Surprisingly, Wnt/β-catenin signaling appears to largely indirectly control epidermal patterning, progenitor cell proliferation, and osteoblast maturation via regulation of a multitude of secondary signals.


Uganda Genome Resource: A rich research database for genomic studies of communicable and non-communicable diseases in Africa.
The Uganda Genome Resource (UGR) is a well-characterized genomic database with a range of phenotypic communicable and non-communicable diseases and risk factors generated from the Uganda General Population Cohort (GPC), a population-based open cohort established in 1989. The UGR comprises genotype data on ∼5,000 and whole-genome sequence data on ∼2,000 Ugandan GPC individuals from 10 ethno-linguistic groups. Leveraging other platforms at MRC/UVRI and LSHTM Uganda Research Unit, there is opportunity for additional sample collection to expand the UGR to advance scientific discoveries. Here, we describe UGR and highlight how it is providing opportunities for discovery of novel disease susceptibility genetic loci, refining association signals at new and existing loci, developing and testing polygenic scores to determine disease risk, assessing causal relations in diseases, and developing capacity for genomics research in Africa. The UGR has the potential to develop to a comparable level of European and Asian large-scale genomic initiatives.


Synthesis of Pt nanoparticles supported on a novel 2D bismuth tungstate/lanthanum titanate heterojunction for photoelectrocatalytic oxidation of methanol.
The combination of different semiconductors to form a heterojunction plays an important role for exploring new visible-light-driven electrocatalysts. Herein, a two-dimensional (2D) Bi2WO6/La2Ti2O7 (LTO) heterojunction has been synthesized and to be as carrier of Pt nanoparticles. Subsequently, electrocatalytic activity and stability of the as-obtained Pt-Bi2WO6/LTO has been evaluated in methanol oxidation reaction (MOR) under the action of visible light and electricity. Results indicate that Pt-Bi2WO6/LTO sample displays excellent catalytic performance and stability with assistance from visible light. Under identical conditions, the current intensity of MOR on the Pt-Bi2WO6/LTO modified electrode is found to reach 1409 mA mg-1Pt, which is 3.92 times higher than the measured Pt-Bi2WO6 modified electrode (359.8 mA mg-1Pt). In addition, the current density of MOR on Pt-Bi2WO6/LTO electrode decreases by 2.85% after scanning for 300 cycles. Furthermore, Pt-Bi2WO6/LTO is 6.99 times more resistant to poisoning than the Pt-Bi2WO6 electrode determines by chronopotentiometry under visible light illumination. The presented results indicate that a Pt-Bi2WO6/LTO nanocomposite is a viable alternative photo-electric catalyst, providing a potential new basis for the future development of catalysts in fuel cell reactions.


Good occlusal practice in the provision of implant borne prostheses.
The increased use of endosseous dental implants means that many dentists will encounter patients with dental implants in their everyday practice. Dental practitioners might be actively involved in the provision of implant borne prostheses at both the surgical and restorative phases, or only at the restorative stage. This section is written for all dentists and aims to examine the subject of occlusion within implantology. It aims to provide guidelines of good occlusal practice to be used in the design of the prosthesis that is supported or retained by one or more implants. As implantology is a 'new' discipline of dentistry, there are fewer standard texts and this section, therefore, is much more extensively referenced than the subjects that have been considered to date.


Different housing conditions for zebrafish: What are the effects?
Zebrafish is a popular experimental model in several research areas but little is known about the effects of using different strains or housing conditions. Poor control of genetic background and housing conditions could affect experimental results and data reproducibility. Here we investigated the effects of two possible sources of variation on zebrafish behaviour: fish origin and environmental parameters (light intensity, water temperature and noise). Zebrafish behaviour was then examined using the 'novel tank test', one of the most common paradigms used to assess anxiety-like behaviours in zebrafish. Our results show that an increase in light intensity alters fish behaviour, particularly freezing duration and distance from the bottom of the tank, indicating increased anxiety. Swimming activity increased at the lowest temperature (25 °C). However, different levels of background noise did not cause any significant changes in behaviour. Differences were also found between zebrafish strains and populations: while the AB strain from laboratory 1 was minimally influenced by variation in holding conditions, the AB strain from laboratory 2 was highly affected by changes in temperature, light, and background noise. Our study shows that variation in strains and holding conditions can significantly influence the results of behavioural testing and should be carefully considered in the experimental design and properly reported to improve data interpretation and reproducibility.


A review on constructive classification framework of research trends in analytical instrumentation for secondary micro(nano)plastics: What is new and what needs next?
Secondary micro(nano)plastics generated from the degradation of plastics pose a major threat to environmental and human health. Amid the growing research on microplastics to date, the detection of secondary micro(nano)plastics is hampered by inadequate analytical instrumentation in terms of accuracy, validation, and repeatability. Given that, the current review provides a critical evaluation of the research trends in instrumental methods developed so far for the qualitative and quantitative determination of micro(nano)plastics with an emphasis on the evolution, new trends, missing links, and future directions. We conducted a meta-analysis of the growing literature surveying over 800 journal articles published from 2004 to 2022 based on the Web of Science database. The significance of this review is associated with the proposed novel classification framework to identify three main research trends, viz. (i) preliminary investigations, (ii) current progression, and (iii) novel advances in sampling, characterization, and quantification targeting both micro- and nano-sized plastics. Field Flow Fractionation (FFF) and Hydrodynamic Chromatography (HDC) were found to be the latest techniques for sampling and extraction of microplastics. Fluorescent Molecular Rotor (FMR) and Thermal Desorption-Proton Transfer Reaction-Mass Spectrometry (TD-PTR-MS) were recognized as the modern developments in the identification and quantification of polymer units in micro(nano)plastics. Powerful imaging techniques, viz. Digital Holographic Imaging (DHI) and Fluorescence Lifetime Imaging Microscopy (FLIM) offered nanoscale analysis of the surface topography of nanoplastics. Machine learning provided fast and less labor-intensive analytical protocols for accurate classification of plastic types in environmental samples. Although the existing analytical methods are justifiable merely for microplastics, they are not fully standardized for nanoplastics. Future research needs to be more inclined towards secondary nanoplastics for their effective and selective analysis targeting a broad range of environmental and biological matrices.


Congenital hydrocephalus in the northeast of Brazil: epidemiological aspects, prenatal diagnosis, and treatment.
Congenital hydrocephalus (CH) has higher proportions in developing countries such as Brazil, reaching rates of 3.16:1,000 newborns. Early diagnosis is essential and can be done during the second trimester of pregnancy, highlighting the importance of regular prenatal care. Our objective is to describe the epidemiological profile of children with CH in the state of Bahia. Consecutive medical records of patients with CH, aged less than 2 years and operated at a pediatric reference hospital between September 2009 and September 2012, were reviewed. One hundred twenty-one children underwent ventricular peritoneal shunt (VP shunt) due to CH. As for prenatal care, 38% of pregnant women did it regularly. Males predominated with 56% of cases with a median age of 3 months, and 68% were from the countryside area. The most frequent clinical manifestations were bulging fontanelle (37%) and increased head circumference (30%). There were 13 (11%) reports of complications associated with VP shunts. There were nine deaths (7%), and respiratory complications were the main cause. Public health measures are the key to increase mothers' knowledge about the importance of regular prenatal monitoring. There was a predominance of male children, with a median age of 3 months, with the majority coming from the countryside.


Isolation of parafluorophenylalanine-resistant mutants from HeLa cell cultures.
This report describes a method to isolate temperature-conditional phenylalanine transport mutants from the transformed human cell line HeLa. Using ultraviolet light as a mutagenic agent and DL-parafluorophenylalanine (PFPA), a poisonous analogue of L-phenylalanine, as a selective agent, mutagenized cells were selected for survival in the presence of PFPA at a temperature of 39 degrees C. Survivors of the mutagenesis and selection procedures were removed from the culture dishes by trypsin and cloned at a temperature of 35 degrees C. Seven of these lines isolated demonstrated continued resistance to PFPA at 39 degrees C. These lines were tested for uptake of L-phenylalanine at an external concentration of 100 microM and for continued resistance to PFPA at two concentrations. Cells were tested at 35 and at 39 degrees C. The data were compared to those obtained for the parental HeLa cell line under identical conditions. The seven mutant cell lines demonstrated varying resistances to PFPA and varying levels of accumulation of L-phenylalanine when tested at 35 and 39 degrees C. Three mutant lines were additionally tested for L-phenylalanine tRNA charging levels and for transport of L-arginine. The lines had parental cell levels of tRNA charging and L-arginine transport which suggest that the induced genetic defect affects a specific L-phenylalanine transport system.


Transferability of robotic console skills by early robotic surgeons: a multi-platform crossover trial of simulation training.
Robotic surgical training is undergoing a period of transition now that new robotic operating platforms are entering clinical practice. As this occurs, training will need to be adapted to include strategies to train across various consoles. These new consoles differ in multiple ways, with some new vendors using flat screen open source 3D enhanced vision with glasses and differences in design will require surgeons to learn new skills. This process has parallels with aviation credentialling across different aircraft described as type rating. This study was designed to test the hypothesis that technical robotic console operating skills are transferrable across different robotic operating platforms. Ten participants sequentially completed four Mimic®(Surgical Science) simulation exercises on two different robotic operating platforms (DaVinci®, Intuitive Surgical and HUGO™ RAS, Medtronic). Ethical approval and informed consent were obtained for this study. Groups were balanced for key demographics including previous robotic simulator experience. Data for simulation metrics and time to proficiency were collected for each attempt at the simulated exercise and analysed. Qualitative feedback on multi-platform learning was sought via unstructured interviews and a questionnaire. Participants were divided into two groups of 5. Group 1 completed the simulation exercises on console A first then repeated these exercises on console B. Group 2 completed the simulated exercises on console B first then repeated these exercises on console A. Group 1 candidates adapted quicker to the second console and Group 2 candidates reached proficiency faster on the first console. Participants were slower on the second attempt of the final exercise regardless of their allocated group. Quality and efficiency metrics and risk and safety metrics were equivalent across consoles. The data from this investigation suggests that console operating skills are transferrable across different platforms. Overall risk and safety metrics are within acceptable limits regardless of the order of progression of console indicating that training can safely occur across multiple consoles contemporaneously. This data has implications for the design of training and certification as new platforms progress to market and supports a proficiency-based approach.


Microarray-based bioinformatics analysis of osteoblasts on TiO2 nanotube layers.
The TiO(2) nanotube layers fabricated by electrochemical anodization have received considerable attention in dentistry and orthopedic medicine due to their increased osseointegration compared with the unanodized titanium. The molecular mechanisms underlying the interactions between nanotubes and osteoblasts is unknown. To examine this, the mRNA expression profile of MG-63 osteoblast-like cells cultured on the TiO(2) nanotubes was explored by DNA microarray. The differentially expressed genes were identified by bioinformatics analysis. Gene ontology (GO) and Go-map network analysis indicated that the TiO(2) nanotubes enhanced osteoblast proliferation and differentiation and decreased osteoblast adhesion and immunization. The expressions of genes were mainly increased in pathways influencing cell proliferation and differentiation (Cell cycle, Terpenoid backbone biosynthesis, and TGF-beta signaling) and were decreased in pathways controlling cell immunization (Cell adhesion molecules (CAMs), Allograft rejection, and Graft-versus-host disease). Signal network analysis generated from differentially expressed genes suggested that CTNNB1 (beta-catenin) was the central gene for increasing osteoblast proliferation and differentiation, and IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) was the central gene for repressing osteoblast immunization on nanotube layers. These two genes were further confirmed by quantitative PCR. The identified signal pathways and central genes in the study are well correlated with osteoblast phenotype. Furthermore, microarray-based bioinformatics analysis is a powerful tool in efficiently understanding molecular mechanisms underlying the interactions between osteoblasts and the nanotube layers.


Endoscopy of the nose and nasopharynx.
Endoscopy of the nose and nasopharynx using rigid endoscopes and the zoom-laryngoscope-epipharyngoscope after v. Stuckrad enhances the diagnostics in these regions considerably. These "inaccessible" regions, remote structures and niches can easily be visualized by angle-endoscopes with magnification. Not only diagnostic procedures are facilitated but also some therapeutical manipulations. Especially for the early detection of cancer as for follow-up control and photo-documentation the endoscopes are of particular importance.


Plant-Based Diets: A Path to Ending CVD as We Know It?
Cardiovascular disease (CVD) is the leading cause of death in the United States, with roughly 700,000 CVD deaths every year [1]. [...].


Risk of CKD in Australian indigenous and nonindigenous children: a population-based cohort study.
Aboriginal Australians have a 9-fold increased risk of end-stage renal disease. There is no information about the natural history and risk of chronic kidney disease (CKD) in Aboriginal and non-Aboriginal children. Using a prospective study design, we aimed to determine the prevalence of persistent markers and risk factors for CKD in Australian Aboriginal and non-Aboriginal children and whether Aboriginal children are at increased risk of persistent markers of CKD after accounting for sociodemographic differences. Children were enrolled from elementary schools throughout New South Wales. Aboriginal (Aboriginal and Torres Strait Islander Australians) versus non-Aboriginal ethnicity. Urine analysis, height, weight, blood pressure, birth weight, and sociodemographic status were measured at baseline and 2-year follow-up. Albuminuria was defined as albumin-creatinine ratio of 3.4 mg/mmol or greater, hematuria as 25 or greater red blood cells/microL (>or=1+), obesity as body mass index of 2 SDs or greater, and systolic and diastolic hypertension as blood pressure greater than the 90th percentile. 2,266 children (55.1% Aboriginal; 51.0% boys; mean age, 8.9 +/- 2.0 years [SD] years) were enrolled at baseline. Early markers and predictors of CKD at baseline were frequent: hematuria (5.5%), albuminuria (7.3%), obesity (7.1%), systolic hypertension (7.2%), and diastolic hypertension (5.8%). 1,432 children (63%) were available for retesting at 2-year follow-up (54.0% Aboriginal; 50.5% boys; mean age, 10.5 +/- 2.0 years). Persistent obesity (5.3%) was frequent, but persistent markers of CKD were infrequent (systolic hypertension, 1.1%; diastolic hypertension, 0.2%; hematuria, 1.1%; and albuminuria, 1.5%). Although there were more Aboriginal than non-Aboriginal children with baseline hematuria (7.1% versus 3.6%; P = 0.001), after adjustment for age, sex, birth weight, and sociodemographic status, there was no increased risk of persistent hematuria, albuminuria, obesity, or hypertension in Aboriginal children. Persistent markers of CKD were much less frequent than anticipated, which may have affected study power. The group lost at follow-up was older children, which may have biased results. Overall, only 20% of children found to have markers of early CKD had persistent abnormalities (diastolic and systolic hypertension, albuminuria, and hematuria) 2 years later, equivalent to a population point prevalence of 1% to 2% in children with a mean age of 10 years. Aboriginal children had greater rates of baseline and transient hematuria, but no increased risk of persistent markers of CKD, suggesting that adolescence and young adulthood is a critical time for preventative strategies.


Phase II feasibility study of high dose epirubicin plus etoposide and cisplatin (HDEEC) regimen in small cell lung cancer.
Seventeen patients with small cell lung cancer entered a phase II trial testing the feasibility of adding high dose epirubicin (100-120 mg/m2, day 1) in combination with etoposide (60-80 mg/m2, days 1-5) and cisplatin (70 mg/m2, day 1) courses repeated every three weeks. Complete responders received thoracic (40 Gy) and prophylactic cranial (30 Gy) irradiation. Sixteen patients were evaluable for response and toxicity. Myelosuppression was the dose-limiting side effect. Neutropenic fever was observed in eight patients (53%) and stomatitis in six (40%). No patient had a greater than 14% decline in the cardiac ejection fraction. Strict adherence to the dose-schedule designed was impossible as doses were trimmed and delayed in 30% of instances. The overall objective response rate was 81% (95% confidence limits, 62% to 100%), in limited disease there were complete remissions in 57%. With a 16 months median follow-up, overall median survival was 13 months. This study was unable to prove the feasibility of epirubicin escalation when added to etoposide-cisplatin combination, hampering the dose-intensification Norton-Simon model test.


Protective effect of telmisartan against endothelial dysfunction after coronary drug-eluting stent implantation in hypertensive patients.
The aim of this prospective, randomized study was to evaluate the effects of telmisartan, compared with the calcium-channel blocker amlodipine, on endothelial function after coronary drug-eluting stent (DES) implantation in hypertensive patients. DES implantation impairs local endothelial function, which may be associated with future cardiovascular events. Telmisartan, which has unique peroxisome proliferator-activated-receptor-gamma-mediated effects in addition to its renin-angiotensin system-inhibition effects, has favorable effects on endothelial function. Fifty-one hypertensive patients with coronary artery stenosis but without coronary artery spasm, treated with a sirolimus-eluting stent, were randomly assigned to either the telmisartan (25 cases) or amlodipine (26 cases) treatment groups. At baseline and at 3 months after DES implantation, endothelium-dependent and -independent vasomotion were evaluated by quantitative coronary angiography under the condition of medication withdrawal. The mean luminal diameter of a 20-mm coronary segment, beginning 5 mm distal to the stent, was measured before and after infusion of intracoronary acetylcholine (10(-7), 10(-6) mol/l) and then again after infusion of nitroglycerin. Blood pressure was comparable between groups at baseline and after 3 months. Vasoconstriction after acetylcholine infusion at 3 months (impaired endothelial function) was less pronounced in the telmisartan group than in the amlodipine group (p<0.0001), although there was no significant difference between the 2 groups before DES implantation. The response to nitroglycerin did not differ between groups before or at 3 months after DES implantation. Telmisartan, compared with amlodipine, significantly ameliorated endothelial dysfunction after DES implantation in terms of vasoconstriction induced by acetylcholine.


Endocytosis of HLA and H-2 molecules on transformed murine cells measured by fluorescence dequenching of liposome-encapsulated carboxyfluorescein.
We have studied internalization of cell surface proteins encoded by genes of the human major histocompatibility complex (HLA) transferred into murine L cells, in comparison with mouse (H-2) histocompatibility determinants. This internalization was measured by the use of monoclonal antibodies directed at these determinants, to which were bound methotrexate- and carboxyfluorescein-containing liposomes covalently coupled to protein A. In addition to the effect of methotrexate on the cells, the technique of fluorescence self-quenching release was used to measure the kinetics of internalization for single cells using a flow cytofluorometer. The native and foreign gene products were internalized in an apparently identical manner. These techniques can be applied to cells expressing genes with altered or deleted segments thus providing a basis for the analysis of the effect of sequence modifications on the internalization of the encoded molecule.


Congenital granuloprival hypoplasia of cerebellar and hippocampal cortex.
Two siblings with congenital granule cell hypoplasia of the cerebellum and hippocampus are reported. The patients, both male, showed severe psychomotor retardation, microcephaly, hypotonia, athetosis, and seizures; they died at the ages of 3 7/12 years and 5 10/12 years, respectively. Postmortem examinations in both cases revealed nearly complete absence of the granule cells of the cerebellum with relative preservation of the Purkinje cells. Also absent were the granule cells of the fascia dentata of the Ammon's horns of the hippocampus, without any detectable gliosis; this has not previously been reported. Twenty-three autopsy cases of granuloprival cerebellar hypoplasia are reviewed. The present cases illustrate a singularly unique disease process, comparable to the classical cerebellar hypoplasia experimentally induced by parvoviruses, and suggest a granule cell specific insult to the brain during the late second trimester.


Thrombogenicity of biomaterials depends on hemodynamic shear rate.
While it is well recognized that different biomaterials induce thrombosis at low shear rates, the effect of high shear rates may be quite different. We hypothesize that the amount of thrombus formation on a given material can be greatly influenced by the local shear rate. We tested this hypothesis with two different whole blood perfusion loop assays to quantify biomaterial thrombogenicity as a function of shear stress. One assay uses obstructive posts (pins) of material positioned centrally in a tube perfused at high shear rate of >5000/s for 24 h. A second assay uses a parallel plate chamber to perfuse low (<150/s), medium (~500/s), and high shear rates over 96 h. We evaluated the thrombogenicity of seven different biomaterials including stainless steel, acrylic, ceramic, Dacron, polytetrafluoroethylene (PTFE), silicone, and polyvinyl chloride (PVC). For the pin assay, thrombus mass was significantly greater for stainless steel than either zirconia ceramic or acrylic (p < 0.001). Similarly, the parallel plate chamber at high shear showed that steel and PTFE (p < 0.02) occluded the chamber faster than acrylic. In contrast, a low shear parallel plate chamber revealed that stainless steel and PTFE were least thrombogenic, while silicone, Dacron, and other plastics such as acrylic were most thrombogenic. Histology revealed that high shear thrombi had a large proportion of platelets not seen in the low shear fibrin-rich thrombi. This differential thrombogenicity based on shear rate conditions may be important in the selection of biomaterials for blood-contacting devices.


Long-term results of scaphoid nonunion treated by intercalated bone grafting and Herbert's screw fixation--a study of 49 patients for at least five years.
The objective of this article is to report our clinical experience in the treatment of patients with scaphoid nonunion using intercalated bone graft and Herbert's screw and the long-term postoperative results with a minimum of five years of follow-up. We retrospectively reviewed 49 patients treated with carved intercalated bone graft and Herbert's screw fixation from September 1987 to June 2001. Preoperative clinical manifestations and postoperative results were assessed by radiography, and functional results, including grip force, range of motion of the wrist joint, and Cooney's scoring chart, were evaluated. The union rate was 93.9%. The average grip power, as well as wrist flexion and extension were significantly improved. Using Cooney's scoring system, 29 patients were rated excellent and 17 good. For successful union, anatomical reduction with carved intercalated bone grafting and Herbert's screw fixation is definitely a reliable option. This method leads to a satisfactory long-term functional outcome.


Extraction and purification of a High Mannose type oligosaccharide from Phaseolus lunatus beans by oxidative release with sodium hypochlorite.
High Mannose glycans (HM) are intermediates for the eukaryotic glycosylation pathway but are not commonly found on mature glycoproteins. HM, particularly Man9GlcNAc2 (M9), are present on the glycan shield of viral envelopes and have received attention as elements for semi-synthetic vaccines. The most common strategy to produce HM is extensive pronase digestion from soybean agglutinin (SBA) to obtain Asn-M9. Storage proteins from Phaseolus lunatus (butter beans) are abundant in M9 and could also be used for M9 production. Chemical alternatives to enzyme-based protocols such as sodium hypochlorite (NaClO) have been used effectively to release N-glycans. Here we present an application of the NaClO glycan release strategy to produce M9 from Phaseolus lunatus beans as an alternative to SBA and the characterisation of some of the release side products that support the release reaction mechanism.


Quality of Life Evaluation in Saudi Arabian Pediatric Patients with Primary Immunodeficiency Diseases Receiving 20% Subcutaneous IgG Infusions at Home.
Subcutaneous immunoglobulin (SCIG) home infusion is widely used as an alternative to intravenous immunoglobulin (IVIG). This study aimed to determine the quality of life (QoL) of patients with primary immunodeficiency (PID) after switching to home-based SCIG. In this prospective open-label single-center study, QoL was determined using the validated Arabic version of the Child Health Questionnaire at baseline and 3 and 6 months after switching from IVIG to SCIG. Twenty-four patients were recruited from July 2018 to August 2021, including 14 females and 10 males. The median age of the patients was 5 years (range, 0-14 years). The patients' diagnoses included severe combined immunodeficiency, combined immunodeficiency, agammaglobulinemia, Omenn syndrome, immunodysregulation, hyper-IgE syndrome, common variable immunodeficiency, and bare lymphocyte syndrome. The median duration on IVIG before inclusion was 40 months (range, 5-125 months). The QoL score showed a significant improvement in the patients' global health at 3 and 6 months compared with those at baseline and a significant improvement in the patients' general health at 3 and 6 months compared with that at baseline. The mean baseline serum IgG trough level was 8.8 ± 2.1 g/L. The mean serum IgG level was significantly higher on SCIG at both 3 and 6 months (11.7 ± 2.3 and 11.7 ± 2.5 g/L, respectively). This is the first study involving an Arab population to show improvement in the QoL of patients with PID after switching from hospital-based IVIG to home-based 20% SCIG.


Strong anti-viral nano biocide based on Ag/ZnO modified by amodiaquine as an antibacterial and antiviral composite.
In this paper, we synthesized Ag/ZnO composite colloidal nanoparticles and the surface of nanoparticles was improved by amodiaquine ligand. The synthesized nanoparticles were characterized using the XRD diffraction pattern, FT-IR Spectroscopy, TEM image, and UV-Vis spectroscopy. The antibacterial, antifungal, and antiviral effects of the synthesized colloid were examined on E.coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus hirae bacteria, and Candida Albicans and form spore aspergillus fungi, also influenza, herpes simplex, and covid 19 viruses. The results indicate more than 7 log removal of the bacteria, fungi, and viruses by synthesized colloid with a concentration of 15 μg/L (Ag)/50 µg/ml (ZnO). This removal for covid 19 virus is from 3.2 × 108 numbers to 21 viruses within 30 s. Also, irritation and toxicity tests of the synthesized colloid show harmless effects on human cells and tissues. These colloidal nanoparticles were used as mouthwash solution and their clinical tests were done on 500 people infected by the coronavirus. The results indicate that by washing their mouth and nose three times on day all patients got healthy at different times depending on the depth of the disease. Almost all people with no signs of infection and using this solution as a mouthwash didn't infect by the virus during the study.


Selective and reversible reduction of odor sensitivity in the rat by concanavalin A.
Rats were trained using an olfactometer to detect low concentrations of ethyl acetate (EA) or dimethyl disulphide vapor (DMDS). Concanavalin A (ConA) applied to the olfactory mucosa had no effect on ability of rats to detect low concentrations of EA but produced a marked deficit in detection in DMDS. DMDS detection performance returned to control levels 3 days after the ConA treatment. These results provide the first behavioral evidence for odor-specific inhibition by chemical modification of the olfactory epithelium and support the notion that ConA selectively inactivates one or more types (subclasses) of olfactory receptor proteins.


Controlling of the bidirectional amplifier chain for optical frequency distribution based on a two-dimensional noise detector.
In the paper we present a solution for controlling the chain of bidirectional optical amplifiers, intended for long-haul fiber links used to distribute signals produced by optical atomic clocks. The solution is based on a dedicated two-channel noise detector, which allows independent measurement of the noise contributions related to interferometric signal fading and additive wideband noise. New signal quality metrics, based on two-dimensional noise detector, allows to distribute properly the needed gain among the chained amplifiers. Experimental results performed both in laboratory conditions and on a real 600 km-long link, confirming proper operation of proposed solutions, are presented.


Growth patterns and gastrointestinal symptoms in pediatric patients after hematopoietic stem cell transplantation.
To identify growth patterns and gastrointestinal (GI) symptoms in pediatric patients during the first four months after hematopoietic stem cell transplantation (HSCT) and to assess whether an association exists between acute graft-versus-host disease (GVHD) and growth pattern changes or GI symptoms. A prospective, longitudinal cohort design. A tertiary children's hospital in a metropolitan area in the southern United States. A convenience sample of 35 pediatric patients receiving allogeneic HSCT. Anthropometric measurements were obtained and GI symptoms were surveyed in pediatric patients before HSCT and two and four months after HSCT. GI symptoms, anthropometric measurements, and presence or absence of acute GVHD. All anthropometric measurements showed a significant change over time; height showed an increase, and weight, skinfold triceps, and mid-arm circumference showed a decrease over the fourmonth measurement period. Eight GI symptoms were prevalent over the four months, and the mean severity and distress scores fluctuated minimally during that time. No statistically significant differences were noted in any of the anthropometric measurements or GI symptoms between pediatric patients with and without GVHD. Pediatric patients in the study exhibited poor growth patterns during the four months after HSCT and experienced multiple GI symptoms before and after HSCT. Nurses should be aware of the importance of evaluating growth and symptom experience in all pediatric patients during HSCT recovery and assist in defining treatment plans that will optimize patient health.


Reported non-compliance with pre-donation screening among blood donors in Québec, Canada: A focus on the 3-month deferral for men who have sex with men.
In Québec (Canada), the donation deferral for men who have sex with men (MSM) has recently been shortened to 3 months. Whether this change impacted compliance with pre-donation screening is unknown. We assessed compliance with the disclosure of male-to-male sex and other behavioural risk factors for HIV amid this change. Québec residents who donated from 14 July 2020 to 30 November 2020 were invited to participate in an online survey. Donors were informed that the survey was optional and anonymous. Survey questions were those used for routine pre-donation screening. Rates of reported non-compliance were weighted based on several characteristics. Of 21,918 contacted donors, 7113 (32.45%) participated. Among male participants (N = 3347), six (0.27% [95% confidence interval (CI) = 0.09%-0.44%]) were not compliant with a 3-month MSM deferral. Among female participants (N = 3766), two (0.06% [95% CI = 0.00%-0.13%]) were not compliant with a 3-month deferral for sex with a man who had male-to-male sex ≤12 months. Other risk factors exhibited similar or lower rates of reported non-compliance. Reported non-compliance with a 3-month MSM deferral and the disclosure of other HIV behavioural risk factors was low. These results warrant the investigation of behavioural donor risk assessment approaches to further improve the inclusiveness of blood donation.


Androgen deprivation causes truncation of the C-terminal region of androgen receptor in human prostate cancer LNCaP cells.
The androgen receptor (AR) acts as a ligand-dependent transcription factor, whereas mutant AR lacking the C-terminal ligand-binding domain functions in a ligand-independent manner. In the present study we report that the C-terminal truncated AR, which we named AR-NH1 (the N-terminal fragment of AR cleaved in the neighborhood of helix 1 of the ligand-binding domain), is produced in LNCaP prostatic carcinoma cells. The AR-NH1 of ~90 kDa was observed in an androgen-independent LNCaP subline and was further accumulated by the proteasome inhibitor MG132. MG132 treatment caused the accumulation of AR-NH1 even in parent LNCaP cells. AR-NH1 was produced in the absence of ligand or in the presence of the AR antagonist bicalutamide, whereas AR agonists suppressed its production. AR-NH1 was detected with different AR antibodies recognizing amino acid residues 1-20 and 300-316 and was also generated from exogenous AR. Both siRNA-mediated AR knockdown and treatment with a serine protease inhibitor (4-(2-aminoethyl)-benzenesulfonyl fluoride) reduced AR-NH1 levels. According to the predicted cleavage site (between amino acid residues 660-685) and its nuclear localization, it is assumed that AR-NH1 functions as a constitutively active transcription factor. These data suggest that AR-NH1 is produced under hormone therapy and contributes to the development of castration-resistant prostate cancer due to its ligand-independent transcriptional activity.


Predicting fluid responsiveness using esophagus Doppler monitoring and pulse oximetry derived pleth variability index; retrospective analysis of a hemodynamic study.
Fluid therapy during major surgery can be managed by providing repeated bolus infusions until stroke volume no longer increases by ≥ 10%. However, the final bolus in an optimization round increases stroke volume by < 10% and is not necessary. We studied how different cut-off values for the hemodynamic indications given by esophagus Doppler monitoring, as well as augmentation by pulse oximetry, are associated with a higher or smaller chance that stroke volume increases by ≥ 10% (fluid responsiveness) before fluid is infused. An esophagus Doppler and a pulse oximeter that displayed the pleth variability index were used to monitor the effects of a bolus infusion in 108 patients undergoing goal-directed fluid therapy during major open abdominal surgery. The analyzed data set comprised 266 bolus infusions. The overall incidence of fluid responsiveness was 44%, but this varied greatly depending on pre-infusion hemodynamics. The likelihood of being fluid-responsive was 30%-38% in the presence of stroke volume > 80 mL, corrected flow time > 360 ms, or pleth variability index < 10%. The likelihood was 21% if stroke volume had decreased by <8% since the previous optimization, which decreased to 0% if combined with stroke volume > 100 mL. By contrast, the likelihood of fluid responsiveness increased to 50%-55% when stroke volume ≤ 50 mL, corrected flow time ≤ 360 ms, or pleth variability index ≥ 10. A decrease in stroke volume by > 8% since the previous optimization was followed by a 58% likelihood of fluid responsiveness that, in combination with any of the other hemodynamic variables, increased to 66%-76%. Single or combined hemodynamic variables provided by esophagus Doppler monitoring and pulse oximetry derived pleth variability index could help clinicians avoid unnecessary fluid bolus infusions.


Comprehension of wh-questions precedes their production in typical development and autism spectrum disorders.
Children with autism spectrum disorders (ASD) rarely produce wh-questions (e.g. "What hit the book?") in naturalistic speech. It is unclear if this is due to social-pragmatic difficulties, or if grammatical deficits are also involved. If grammar is impaired, production of wh-questions by rote memorization might precede comprehension of similar forms. In a longitudinal study, 15 children with ASD and 18 initially language-matched typically developing (TD) toddlers were visited in their homes at 4-month intervals across a 3-year period. The wh-question task was presented via intermodal preferential looking. Silent "hitting" events (e.g. an apple hitting a flower) were followed by test trials in which the apple and flower were juxtaposed on the screen. During test trials, subject-wh- and object-wh-question audios were sequentially presented (e.g. "What hit the flower?" or "What did the apple hit?"). Control audios were also presented (e.g. "Where's the apple/flower?"). Children's eye movements were coded off-line, frame by frame. To show reliable comprehension, children should look longer to the named item (i.e. apple or flower) during the "where" questions but less at the named item during the subject-wh and object-wh-questions. To compare comprehension to production, we coded 30-min spontaneous speech samples drawn from mother-child interactions at each visit. Results indicated that comprehension of subject- and object-wh-questions was delayed in children with ASD compared with age-matched TD children, but not when matched on overall language levels. Additionally, both groups comprehended wh-questions before producing similar forms, indicating that development occurred in a similar manner. This paper discusses the implications of our findings for language acquisition in ASD.


Structure, Organization, and Expression of the Alpha Prolamin Multigenic Family Bring New Insights into the Evolutionary Relationships among Grasses.
Prolamins are the major seed storage proteins of grasses. In maize and related species, prolamins are classified into α-, β-, γ-, and δ-subclasses by their solubility properties. α-prolamins are encoded by multigene families and have a secondary structure that consists of tandem α-helix repeats. Maize has two α-prolamin subclasses, namely the 19 and 22 kDa subclasses that contain nine and 10 α-helix repeats, respectively. Here, we present an evolutionary study based on the structure, organization, and expression of α-prolamins in maize, sugarcane, sorghum, and coix. True 22 kDa subclasses containing 10 repeats are conserved in all four species, but true 19 kDa subclasses containing nine repeats are found only in maize and sugarcane. We discovered a 19 kDa-like α-coixin that, as in sorghum, is encoded by few genes. These data suggest that a 19 kDa progenitor present in the ancestor common to maize, coix, sorghum, and sugarcane was preserved at low copy number in coix and sorghum, while amplified into multigene family architecture in maize and sugarcane. The expression profiling of α-prolamins, verified by two-dimensional gels, showed highly conserved multispot composition for the 19 kDa α-prolamins in maize and sugarcane. Coix and sorghum did not present true 19 kDa α-prolamin spots. Our data show remarkable similarity between maize and sugarcane 19 kDa α-prolamins regarding both gene structure and expression. Since the multigene architecture of 19 kDa α-canein appeared after sugarcane diverged from sorghum, our data suggest that maize and sugarcane might have acquired the multigene family encoding these storage proteins from a common ancestor.


Detecting and treating retinopathy in patients with type I diabetes mellitus. A health policy model.
Diabetic retinopathy is the major cause of new cases of blindness among working-age Americans. The authors analyzed the medical and economic implications of alternative screening strategies for detecting retinopathy in a diabetic population. The approaches compared included dilated fundus examination at 6-, 12-, and 24-month intervals with and without fundus photography. Potential savings from screening and treatment are based on amounts paid by the federal government for blindness-related disability. Screening for and treating retinopathy in patients with type I diabetes mellitus was cost-effective using all screening strategies. Between 71,474 and 85,315 person years of sight and 76,886 and 94,705 person years of reading vision can be saved for each annual cohort of patients with type I diabetes mellitus when proper laser photocoagulation is administered. This results in a cost savings of $62.1 to $108.6 million. Annual examination of all diabetic patients and semi-annual examination of those with retinopathy was more effective than annual examination with fundus photography. This screening strategy is consistent with the Preferred Practice Pattern for Diabetic Retinopathy of the American Academy of Ophthalmology.


Morphological findings of different areas of gastric mucosa in patients with achlorhydria, extreme hypochlorhydria, normochlorhydria and their relationship to serum gastrin levels: evidence for two different types of gastritis.
The morphological changes of gastric mucosa taken from different areas has been studied in patients of approximately the same age with achlorhydria, extreme hypochlorhydria and normochlorhydria. The serum gastrin level and parietal cell antibodies were determined in the achlorhydric parietal cell antibodies were determined in the achlorhydric patients. In the latter the diffuse gastritis was localized in the corpus-fundic area, while the changes in the antral region were few and occurred mostly in the superficial zone. In normochlorhydric patients however, the diffuse gastritis was localized in the antral region, with only few changes at the corpus-fundic area. In patients with extreme hypochlorhydira either the fundic or the antral region was involved. Besides the diffuse gastritis intestinal metaplasia, pseudopyloric metaplasia, and atrophy of mucosa were also observed, although much less commonly. The increase of gastrin level could not be related to a definite morphological pattern in the gastric mucosa. It can be assumed that each of the two types of gastritis has a different natural history; the antral site of gastrititis cannot be transformed into the fundic site, nor can the fundic site be transformed into the antral site.


Thiol-mediated oxidation of nonphenolic lignin model compounds by manganese peroxidase of Phanerochaete chrysosporium.
In the presence of MnII, H2O2, and glutathione (GSH), manganese peroxidase oxidized veratryl alcohol (I) to veratraldehyde (IV). Anisyl alcohol (II) and benzyl alcohol (III) were also oxidized by this system to their corresponding aldehydes (V and VI). In the presence of GSH, chemically prepared MnIII or gamma-irradiation also catalyzed the oxidation of I, II, and III to IV, V, and VI, respectively. GSH and dithiothreitol rapidly reduced MnIII to MnII in the absence of aromatic substrates and the dithiothreitol was oxidized to its disulfide (4,5-dihydroxyl-1,2-dithiane). These results indicate that the thiol is oxidized by enzyme-generated MnIII to a thiyl radical. The latter abstracts a hydrogen from the substrate, forming a benzylic radical which reacts with another thiyl radical to yield an intermediate which decomposes to the benzaldehyde product. In the presence of MnII, GSH, and H2O2, manganese peroxidase also oxidized 1-(4-ethoxy-3-methoxy-phenyl)-2-(4'-hydroxymethyl-2'-methoxyphenoxy)- 1,3-dihydroxypropane (XII) to yield vanillyl alcohol (VII), vanillin (VIII), 1-(4-ethoxy-3-methoxyphenyl)-1,3-dihydroxypropane (XVI), 1-(4-ethoxy-3-methoxyphenyl)-1-oxo-3-hydroxypropane (XIX), and several C alpha oxidized dimeric products. Abstraction of the C alpha (A ring) hydrogen of the dimer (XII) yields a benzylic radical, leading to C beta oxygen ether cleavage. The resultant intermediates yield the ketone (XIX) and vanillyl alcohol (VII) or vanillin (VIII). Alternatively, benzylic radical formation at the C' alpha position (B ring) leads to radical cleavage, yielding a quinone methide and a C beta radical, which yield vanillin and the 1,3-diol (XVI), respectively. In these reactions, MnIII oxidizes a thiol to a thiyl radical which subsequently abstracts a hydrogen from the substrate to form a benzylic radical. The latter undergoes nonenzymatic reactions to yield the final products.


Origin of plasmid-mediated quinolone resistance determinant QnrA.
Plasmid-mediated resistance to quinolones is increasingly reported in studies of Enterobacteriaceae. Using a PCR-based strategy, a series of gram-negative species were screened for qnrA-like genes. Shewanella algae, an environmental species from marine and fresh water, was identified as its reservoir. This is a one of the very few examples of progenitor identification of an acquired antibiotic resistance gene.


Lactate facilitates classical swine fever virus replication by enhancing cholesterol biosynthesis.
An emerging topic in virology is that viral replication is closely linked with the metabolic reprogramming of host cells. Understanding the effects of reprogramming host cell metabolism due to classical swine fever virus (CSFV) infection and the underling mechanisms would facilitate controlling the spread of classical swine fever (CSF). In the current study, we found that CSFV infection enhanced aerobic glycolysis in PK-15 cells. Blocking glycolysis with 2-deoxy-d-glycose or disrupting the enzymes PFKL and LDHA decreased CSFV replication. Lactate was identified as an important molecule in CSFV replication, independent of the pentose phosphate pathway and tricarboxylic acid cycle. Further analysis demonstrated that the accumulated lactate in cells promoted cholesterol biosynthesis, which facilitated CSFV replication and disrupted the type I interferon response during CSFV replication, and the disruption of cholesterol synthesis abolished the lactate effects on CSFV replication. The results provided more insights into the complex pathological mechanisms of CSFV.


Excluded volume effect on the electrophoretic mobility of colloidal particles.
In a recent work [J. Colloid Interface Sci. 316 (2007) 196] we studied the influence of the excluded volume effect on spatial distributions of ionic species and electrostatic potential in the neighborhood of a suspended spherical particle. It was shown that the excluded volume effect considerably increases the surface potential (for a given value of the particle charge) as compared to the case when ideal ion behavior is assumed. In the present work we extend our previous equilibrium results to the perturbed/nonequilibrium problem and analyze the effect of ion size constraints on the electrophoretic mobility of a rigid spherical particle immersed in a general electrolyte solution. We find that the electrophoretic mobility always increases with the excluded volume effect, which might broaden the range of experimental data that can be interpreted, including those cases where the measured mobility exceeded the theoretical maximum value predicted by the standard model.


Direct and indirect effects of muscimol on medial vestibular nucleus neurones in guinea-pig brainstem slices.
Inhibitory amino acids are considered as major transmitters in the vestibular system. Using intracellular recordings in slices, we applied gamma-aminobutyric acid (GABA) and muscimol (a specific agonist of the GABAA receptor) to the two main types of medial vestibular nucleus neurones (A and B MVNn). In either a high Mg2+/low Ca2+ solution, or a solution containing tetrodotoxin, all MVNn were hyperpolarized by GABA and muscimol. This indicates that both types of MVNn are endowed with postsynaptic, hyperpolarising GABAA receptors. In a normal medium, about half of A and B MVNn were, in contrast, depolarised by GABA and muscimol, whereas the remaining cells were hyperpolarised. These results could be due to a modulation by GABA and muscimol of a tonic GABA release in the slice. Such a release was, indeed, suggested by results showing the depolarising effect of either tetrodotoxin (TTX) or bicuculline, when applied alone. The cells that were depolarised by GABA or muscimol in control conditions were always hyperpolarised in the presence of TTX. Our data therefore suggest that GABA acting at GABAA receptors in the medial vestibular nucleus can play a role either through a postsynaptic hyperpolarising action or indirectly by inhibiting a tonic GABA release, probably resulting from the spontaneous activity of local inhibitory interneurones. A GABAergic regulation of these interneurones could be important in processes of vestibular habituation and/or adaptation.


Superoxide dismutase: a key target for the neuroprotective effects of curcumin.
Over the past few years, the prevalence of neurodegenerative diseases (NDD) has increased dramatically. The community health system is burdened by the high healthcare costs associated with NDD. Superoxide dismutase (SOD) is a type of metalloenzyme that possesses a distinct characteristic of protecting the body from oxidative stress through antioxidants. In this way, SOD supplementation may activate the endogenous antioxidant mechanism in various pathological conditions and could be used to neutralize free radical excess. Several factors are responsible for damaging DNA and RNA in the body, including the overproduction of reactive species, particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS). Excessive ROS/RNS have deleterious effects on mitochondria and their metabolic processes, mainly through increased mitochondrial proteins, lipids and DNA oxidation. Studies have shown that oxidative stress is implicated in the etiology of many diseases, including NDD. It is thought that anti-inflammatory compounds, particularly phytochemicals, can interfere with these pathways and regulate inflammation. Extensive experimental and clinical research has proven that curcumin (Cur) has anti-inflammatory and anti-neurologic properties. In this review, we have compiled the available data on Cur's anti-inflammatory properties, paying special attention to its therapeutic impact on NDD through SOD.