Discovery of Viruses and Virus-Like Pathogens in Pistachio using High-Throughput Sequencing.
Pistachio (Pistacia vera L.) trees from the National Clonal Germplasm Repository (NCGR) and orchards in California were surveyed for viruses and virus-like agents by high-throughput sequencing (HTS). Analyses of sequence information from 60 trees identified a novel virus, provisionally named "Pistachio ampelovirus A" (PAVA), in the NCGR that showed low amino acid sequence identity (approximately 42%) compared with members of the genus Ampelovirus (family Closteroviridae). A putative viroid, provisionally named "Citrus bark cracking viroid-pistachio" (CBCVd-pis), was also found in the NCGR and showed approximately 87% similarity to Citrus bark cracking viroid (CBCVd, genus Cocadviroid, family Pospiviroidae). Both PAVA and CBCVd-pis were graft transmissible to healthy UCB-1 hybrid rootstock seedlings (P. atlantica × P. integerrima). A field survey of 123 trees from commercial orchards found no incidence of PAVA but five (4%) samples were infected with CBCVd-pis. Of 675 NCGR trees, 16 (2.3%) were positive for PAVA and 172 (25.4%) were positive for CBCVd-pis by reverse-transcription polymerase chain reaction. Additionally, several contigs across multiple samples exhibited significant sequence similarity to a number of other plant virus species in different families. These findings require further study and confirmation. This study establishes the occurrence of viral and viroid populations infecting pistachio trees.


Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients With Metastatic Urothelial Carcinoma.
Effective treatment of locally advanced or metastatic urothelial carcinoma (mUC) remains an unmet need. Antibody-drug conjugates (ADCs) providing targeted drug delivery have shown antitumor activity in this setting. AGS15E is an investigational ADC that delivers the cytotoxic drug monomethyl auristatin E to cells expressing SLITRK6, a UC-associated antigen. This was a multicenter, single-arm, phase 1 dose-escalation and expansion trial of AGS15E in patients with mUC (NCT01963052). During dose escalation, AGS15E was administered intravenously at 6 levels (0.10, 0.25, 0.50, 0.75, 1.00, 1.25 mg/kg), employing a continual reassessment method to determine dose-limiting toxicities (DLTs) and the recommended phase 2 dose (RP2D) for the dose-expansion cohort. The primary objective was to evaluate the safety and pharmacokinetics of AGS15E in patients with and without prior chemotherapy, and with prior checkpoint inhibitor (CPI) therapy. Best overall response was also examined. Ninety-three patients were recruited, including 33 patients previously treated with CPIs. The most common treatment-emergent adverse events were fatigue (54.8%), nausea (37.6%), and decreased appetite (35.5%). Peripheral neuropathy and ocular toxicities occurred at doses of ≥0.75 mg/kg. AGS15E increased in a dose-proportional manner after single- and multiple-dose administration; accumulation was low. Five DLTs occurred from 0.50‒1.25 mg/kg. The RP2D was assessed at 1.00 mg/kg; the objective response rate (ORR) was 35.7% at this dose level. The ORRs in the total population and CPI-exposed subgroup were 18.3% and 27.3%, respectively. DLTs with AGS15E were observed at 0.75, 1.00, and 1.25 mg/kg, with an RP2D of 1.00 mg/kg being determined.


Organic-inorganic telechelic molecules: solution properties from simulations.
We report molecular dynamics simulations for telechelic molecules composed of two polyhedral oligomeric silsesquioxane (POSS) cages connected by one hydrocarbon backbone dissolved in liquid normal hexane. Silsesquioxanes are novel hybrid organic-inorganic molecules that are useful as building blocks for the synthesis of nanostructured materials. By including POSS molecules within a polymeric material it is possible to modify mechanical properties such as resistance to heat and glass transition temperatures. Unfortunately, the molecular mechanisms responsible for these enhancements are at present not completely understood. In an effort to elucidate the molecular phenomena responsible for these effects, we have studied the conformation of telechelic POSS molecules in solution, as well as their self-diffusion coefficients, as a function of the length of the hydrocarbon backbone. We focus on molecules in which the radius of gyration of the alkane backbone is comparable to the size of the silsesquioxane cages. Our results indicate that the backbone has a significant influence on both the equilibrium and the transport properties of dissolved telechelic hybrid molecules. These observations are useful for developing strategies to direct the self-assembly of nanostructured materials.


Advances in rehabilitation of stoma patients.
The rehabilitation of people with abdominal stomas depends upon a good stoma well placed, the guidance of an enterstomal therapist, and the availability of a clinic staffed with a multidisciplinary group to recognize and meet the continuing needs of stoma patients.


Enhanced Gas Sensitivity and Sensing Mechanism of Network Structures Assembled from α-Fe2O3 Nanosheets with Exposed {104} Facets.
Network structures assembled from α-Fe2O3 nanosheets with exposed {104} facets were successfully prepared by heating Fe(NO3)3 solution containing polyvinylpyrrolidone (PVP) in air. The α-Fe2O3 nanosheet-based network structures demonstrate significantly higher response to ethanol and triethylamine than α-Fe2O3 commercial powders. The excellent sensing performances can be ascribed to the exposed (104) facet terminated with Fe atoms. A concept of the unsaturated Fe atoms serving as the sensing reaction active sites is thus proposed, and the sensing reaction mechanism is described at the atomic and molecular level for the first time in detail. The concept of the surface metal atoms with dangling bonds serving as active sites can deepen understanding of the sensing and other catalytic reaction mechanisms and provides new insight into the design and fabrication of highly efficient sensing materials, catalysts, and photoelectronic devices.


Serine-70 is one of the critical sites for drug-induced Bcl2 phosphorylation in cancer cells.
Taxoids and other microtubule-damaging drugs are known to induce Bcl2 phosphorylation at the G2-M phase of the cell cycle, with concomitant apoptosis in malignant cells derived from a variety of human malignancies, including leukemia, lymphoma, and breast and prostate cancer. We have investigated the ability of another antineoplastic drug, dolastatin 10, in inducing Bcl2 phosphorylation and apoptosis. We also investigated the effects of a phosphatase inhibitor okadaic acid in the regulation of Bcl2 phosphorylation, cell cycle arrest, and programmed cell death. Moreover, site-directed mutagenesis studies were performed to determine the specific serine residue(s) responsible for drug-induced Bcl2 phosphorylation. Our results indicate that these antimicrotubule agents or okadaic acid can induce posttranslational modification (phosphorylation) of Bcl2 protein at multiple serine residues. Interestingly, mutation of a serine residue at position 70 to alanine can significantly decrease drug-induced posttranslational modification (phosphorylation) of Bcl2 protein. Apparently, Ser70 seems to be a critical site for drug-induced posttranslational modification (phosphorylation) of the Bcl2 protein.


Environmental exposures and pediatric kidney function and disease: A systematic review.
Environmental chemical exposures have been implicated in pediatric kidney disease. No appraisal of the available evidence has been conducted on this topic. We performed a systematic review of the epidemiologic studies that assessed association of environmental exposures with measures of kidney function and disease in pediatric populations. The search period went through July 2016. We found 50 studies that met the search criteria and were included in this systematic review. Environmental exposures reviewed herein included lead, cadmium, mercury, arsenic, fluoride, aflatoxin, melamine, environmental tobacco, bisphenol A, dental procedures, phthalates, ferfluorooctanoic acid, triclosan, and thallium/uranium. Most studies assessed environmental chemical exposure via biomarkers but four studies assessed exposure via proximity to emission source. There was mixed evidence of association between metal exposures, and other non-metal environmental exposures and pediatric kidney disease and other kidney disease biomarkers. The evaluation of causality is hampered by the small numbers of studies for each type of environmental exposure, as well as lack of study quality and limited prospective evidence. There is a need for well-designed epidemiologic studies of environmental chemical exposures and kidney disease outcomes.


Chemical Analysis of Complex Surface-Adsorbed Molecules and Their Reactions by Means of Cluster-Induced Desorption/Ionization Mass Spectrometry.
Desorption/ionization induced by neutral SO2 clusters (DINeC) is used for mass spectrometry (MS) of surface-adsorbed molecules. The method is shown to be a surface-sensitive analysis tool capable of detecting molecular adsorbates in a wide range of molecular weights as well as their reactions on surfaces, which are otherwise difficult to access. Two different surface/adsorbate systems prepared by means of electrospray ion beam deposition (ES-IBD) were investigated: For the peptide angiotensin II on gold, intact molecules were desorbed from the surface when deposited by soft landing ES-IBD. By comparison to the well-controlled amount of substance deposited by ES-IBD, the sensitivity of DINeC-MS was shown to be on the order of 0.1% of a monolayer coverage, corresponding to femtomoles of analyte. Depending on deposition and sample conditions, the original state of charge of the molecules could be retrieved. Reaction of the adsorbed molecules both with surface atoms as well as with coadsorbed D2O was monitored. Rhodamine 6G was also desorbed as an intact molecule when deposited with kinetic energies below 50 eV. For higher deposition energy, fragmentation of the dye molecules was observed by means of DINeC-MS.


Within leaf variation is the largest source of variation in agroinfiltration of Nicotiana benthamiana.
Transient gene expression utilizing syringe agroinfiltration offers a simple and efficient technique for different transgenic applications. Leaves of Nicotiana benthamiana show reliable and high transformation efficiency, but in quantitative assays also a certain degree of variation. We used a nested design in our agroinfiltration experiments to dissect the sources of this variation. An intron containing firefly luciferase gene was used as a reporter for agroinfiltration. A number of 6 week old tobacco plants were infiltrated for their top leaves, several samples were punched from the leaves after 2 days of transient expression, and protein extracts from the samples were repeatedly measured for luciferase activity. Interestingly, most of the variation was due to differences between the sampling spots in the leaves, the next important source being the different leaves on each plant. Variation between similar experiments, between plants and between repetitive measurements of the extracts could be easily minimized. Efforts and expenditure of agroinfiltration experiments can be optimized when sources of variation are known. In summary, infiltrate more plants but less leaves, sample more positions on the leaf but run only few technical replicates.


Effects of thermal treatments and storage on pectin methylesterase and peroxidase activity in freshly squeezed orange juice.
A specific indicator of freshness, allowing routine distinction between freshly squeezed orange juices (FSOJs) and FSOJ-like products, was to be identified. Using the Actijoule unit of a tubular heater at a flow rate of 60 L/h, FSOJs from Citrus sinensis (L.) Osbeck cv. Valencia Late were continuously heated on a pilot plant scale at six different temperatures (42-92 degrees C), followed by continuous cooling to ambient temperature and subsequent filling into sterilized glass jars. The cloud stability and residual activities of pectin methylesterase (PE) and peroxidase (POD) were monitored over the storage at 4 degrees C for up to 62 days, thus considering the storage conditions of FSOJs in retail markets. As shown by the viable microbial counts throughout storage, microbial activity was insignificant due to good sanitary practice, thus proving that the enzyme activities detected were of plant origin. The juices processed at temperatures > or =62 degrees C were characterized by minor residual activities. When exposed to temperatures <62 degrees C in the genuine acidic matrix of the juices, the heat stability of PE exceeded that of POD. Compared with the aforementioned samples, the juice processed at 52 degrees C with a residual PE activity of 33.8% was hardly inferior in terms of cloud stability within the first 14 days. After the juice was processed at 42 degrees C, rapid clarification occurred within the first 8 days, consistent with undetectable PE deactivation. Hence, only the range of approximately 50-60 degrees C is relevant in minimal heat-processing for the retention of cloud stability within the short turnover period of FSOJ-like products, with partial PE and POD deactivation being already sufficient to distinguish those juices from FSOJs. Irrespective of the previous thermal treatment, the total PE activity remained nearly constant during storage, whereas the POD activity rapidly declined to minor levels after 20 days. Consequently, as to the future analysis of samples with unknown processing history, PE was suggested as an indicator enzyme for the freshness of FSOJs, allowing their unambiguous distinction from minimally heat-processed juices.


Computer modeling and ex vivo experiments with a (saline-linked) irrigated electrode for RF-assisted heating.
Externally irrigated radiofrequency (RF) electrodes have been widely used to thermally ablate tumors in surface tissue and to thermally coagulate the transection plane during a surgical resection. As far as we know, no mathematical model has yet been developed to study the electrical and thermal performance of these electrodes, especially the role of the saline layer that forms around the electrode. Numerical models of a TissueLink device model DS3.0 (Salient Surgical Technologies, Portsmouth, NH, USA) were developed. Irrigation was modeled including a saline layer and a heat convection term in the governing equation. Ex vivo experiments based on fragments of bovine hepatic tissue were conducted to obtain information which was used in building the numerical model. We compared the 60°C isotherm of the computer results with the whitening contour in the heated samples. Computer and experimental results were in fine agreement in terms of lesion depth (2.4 mm in the simulations and 2.4 ± 0.6 mm in the experiments). In contrast, the lesion width was greater in the simulation (9.6 mm vs. 7.8 ± 1.8 mm). The computer simulations allowed us to explain the role of the saline layer in creating the thermal lesion. Impedance gradually decreased as heating proceeded. The saline was not observed to boil. In the proximity of the electrode (around 1 mm) the thermal lesion was mainly created by the RF power in this zone, while at a further distance the thermal lesion was created by the hot saline on the tissue surface by simple thermal conduction. Including the heat convection term associated with the saline velocity in the governing equation was crucial to verifying that the saline layer had not reached boiling temperature. The model reproduced thermal performance during heating in terms of lesion depth, and provided an explanation for: 1) the relationship between impedance, electrode insertion depth, and saline layer, and 2) the process of creating thermal lesions in the tissue with this type of electrode.


Characterization of N200 and P300: selected studies of the Event-Related Potential.
The Event-Related Potential (ERP) is a time-locked measure of electrical activity of the cerebral surface representing a distinct phase of cortical processing. Two components of the ERP which bear special importance to stimulus evaluation, selective attention, and conscious discrimination in humans are the P300 positivity and N200 negativity, appearing 300 ms and 200 ms post-stimulus, respectively. With the rapid proliferation of high-density EEG methods, and interdisciplinary interest in its application as a prognostic, diagnostic, and investigative tool, an understanding of the underpinnings of P300 and N200 physiology may support its application to both the basic neuroscience and clinical medical settings. The authors present a synthesis of current understanding of these two deflections in both normal and pathological states.


Components of depressed mood in married men and women. The Center for Epidemiologic Studies' Depression Scale.
The Center for Epidemiologic Studies' Depression Scale (CES-D) was developed to measure depressive symptoms in community populations. To be useful for epidemiologic studies of depression, the scale should measure the same thing in various subgroups. This study examines the psychometric properties of the CES-D among men and women, including its factor structure, reliability, and characteristics of its subscales. A national sample of 1,360 married men and women, collected in 1978, was used. Factor analysis produced four major factors in the CES-D: depressed affect, enervation , lack of positive affect, and interpersonal problems. These factors are generalizable across men and women with two exceptions--crying spells, which are a good indicator of depressed mood for women, do not indicate depressed mood for men; and feeling one's life is a failure is associated with depressed affect for women and with a lack of positive affect for men. The two items in the interpersonal factor (feeling that people dislike you and that people are unfriendly ) do not show the expected pattern of association with gender, since men have significantly more interpersonal symptoms than women. Women have more symptoms of depressed affect, enervation , and lack of positive affect.


Simulation Model for Laparoscopic Foregut Surgery: The University of North Carolina Foregut Model.
A significant gap presently exists between box-lap and virtual-reality simulators and live surgery. Live animal and cadaver use has significant downsides. We have developed a high fidelity, real tissue simulator that allows training in laparoscopic foregut operations. Our foregut surgery model is based on porcine tissue blocks that include lungs, heart, aorta, esophagus, diaphragm, stomach, duodenum, liver, and spleen. The tissue block is mounted in a human mannequin and perfused with artificial blood. The anterior abdominal wall is constructed so as to allow for laparoscopic or robotic surgical training. We sought to test the model with procedures performed by expert surgeons. After completing the procedures, face validity was measured by surgeon responses to a questionnaire defining the perceived relationship to real surgery. Five expert foregut surgeons performed laparoscopic Heller myotomy, Nissen fundoplication, and sleeve gastrectomy on the model. The simulator was rated as highly realistic in terms of tissue feel, instrument usage, and conduct of the operation for all three procedures. In addition, all surgeons felt the model could significantly shorten the learning curve for performing these procedures. The results of this study show that our simulation model, based on animal tissue blocks, offers a very realistic representation of laparoscopic foregut operations, thus achieving a high level of face validity. The model should be very useful for training surgeons in laparoscopic foregut procedures.


Is patellar denervation necessary in total knee arthroplasty without patellar resurfacing?
To conduct a meta-analysis with randomized controlled trials (RCTs) published in full text to determine the effectiveness of patellar denervation (PD) in primary total knee arthroplasty (TKA). Literature search was performed in PubMed, Embase, Web of Science and Cochrane Library for information from the earliest date of data collection to February 2015. RCTs comparing the benefits and risks of PD with those of no patellar denervation (NPD) in primary TKAs were included. Statistical heterogeneity was quantitatively evaluated by X(2) test with the significance set P < 0.10 or I (2) > 50 %. Six RCTs consisting of 751 patients were included. The incidences of AKP in PD group and NPD group were 38.3 % (90/235) and 46.3 % (107/231), respectively. Meta-analysis showed significant prevention effect of PD on the incidence of AKP (OR 0.65; 95 % CI 0.42, 1.00; P = 0.05) without significant heterogeneity (I (2) = 44 %, P = 0.15). Our results also indicated that PD was significantly associated with better American Knee Society knee (WMD = 2.50; 95 % CI 0.34, 4.67; P = 0.02) and functional scores (WMD = 4.07; 95 % CI 1.34, 6.80; P = 0.0003) and range of motion (ROM) (WMD = 4.27; 95 % CI 1.95, 6.60; P = 0.0003) compared with NPD. However, there was no significant difference between the two groups no matter in Oxford knee score, patellar score or visual analogue scale at any other time. Complications and revisions did not differ significantly between the two groups. This meta-analysis showed that PD in TKAs without patellar resurfacing, compared with NPD, could prevent the incidence of post-operative AKP and improve clinical outcome in KSS and post-operative ROM. Based on the above results, PD was a safe procedure with no significant complications and revision or re-operations. Therapeutic study, Level II.


Therapeutic Role of Functional Components in Alliums for Preventive Chronic Disease in Human Being.
Objectives. Functional components in alliums have long been maintained to play a key role in modifying the major risk factors for chronic disease. To obtain a better understanding of alliums for chronic disease prevention, we conducted a systematic review for risk factors and prevention strategies for chronic disease of functional components in alliums, based on a comprehensive English literature search that was conducted using various electronic search databases, especially the PubMed, ISI Web of Science, and CNKI for the period 2007-2016. Allium genus especially garlic, onion, and Chinese chive is rich in organosulfur compounds, quercetin, flavonoids, saponins, and others, which have anticancer, preventive cardiovascular and heart diseases, anti-inflammation, antiobesity, antidiabetes, antioxidants, antimicrobial activity, neuroprotective and immunological effects, and so on. These results support Allium genus; garlic and onion especially may be the promising dietotherapeutic vegetables and organopolysulfides as well as quercetin mechanism in the treatment of chronic diseases. This review may be used as scientific basis for the development of functional food, nutraceuticals, and alternative drugs to improve the chronic diseases.


Analysis of energetic and exergetic efficiency, and environmental benefits of biomass integrated gasification combined cycle technology.
The problem of the high carbon dioxide emissions linked to power generation makes necessary active research on the use of biofuels in gas turbine systems as a promising alternative to fossil fuels. Gasification of biomass waste is particularly of interest in obtaining a fuel to be run in gas turbines, as it is an efficient biomass-to-biofuel conversion process, and an integration into a combined cycle power plant leads to a high performance with regard to energetic efficiency. The goal of this study was to carry out an energetic, exergetic and environmental analysis of the behaviour of an integrated gasification combined cycle (IGCC) plant fuelled with different kinds of biomass waste by means of simulations. A preliminary economic study is also included. Although a technological development in gasification technology is necessary, the results of simulations indicate a high technical and environmental interest in the use of biomass integrated gasification combined cycle (BioIGCC) systems for large-scale power generation from biomass waste.


Biochemical phenotypes to discriminate microbial subpopulations and improve outbreak detection.
Clinical microbiology laboratories worldwide constitute an invaluable resource for monitoring emerging threats and the spread of antimicrobial resistance. We studied the growing number of biochemical tests routinely performed on clinical isolates to explore their value as epidemiological markers. Microbiology laboratory results from January 2009 through December 2011 from a 793-bed hospital stored in WHONET were examined. Variables included patient location, collection date, organism, and 47 biochemical and 17 antimicrobial susceptibility test results reported by Vitek 2. To identify biochemical tests that were particularly valuable (stable with repeat testing, but good variability across the species) or problematic (inconsistent results with repeat testing), three types of variance analyses were performed on isolates of K. pneumonia: descriptive analysis of discordant biochemical results in same-day isolates, an average within-patient variance index, and generalized linear mixed model variance component analysis. 4,200 isolates of K. pneumoniae were identified from 2,485 patients, 32% of whom had multiple isolates. The first two variance analyses highlighted SUCT, TyrA, GlyA, and GGT as "nuisance" biochemicals for which discordant within-patient test results impacted a high proportion of patient results, while dTAG had relatively good within-patient stability with good heterogeneity across the species. Variance component analyses confirmed the relative stability of dTAG, and identified additional biochemicals such as PHOS with a large between patient to within patient variance ratio. A reduced subset of biochemicals improved the robustness of strain definition for carbapenem-resistant K. pneumoniae. Surveillance analyses suggest that the reduced biochemical profile could improve the timeliness and specificity of outbreak detection algorithms. The statistical approaches explored can improve the robust recognition of microbial subpopulations with routinely available biochemical test results, of value in the timely detection of outbreak clones and evolutionarily important genetic events.


Serum apolipoprotein j in health, coronary heart disease and type 2 diabetes mellitus.
Apolipoprotein (apo) J, clusterin, is ubiquitously expressed in many tissues, and is a component of high-density lipoproteins (HDLs). There is experimental evidence that it may be anti-atherogenic through its effects on cholesterol transport, smooth muscle cell proliferation and lipid peroxidation. HDLs containing apo J and apo A-I carry paraoxonase (PON1), which protects low-density lipoproteins from oxidative modification; however, the extent to which apo J affects coronary heart disease (CHD) is not known. We have developed a sandwich ELISA that enables apo J to be assayed in the range of 13-200 microg/mL. Serum apo J was 52.8+/-0.8 microg/mL (mean+/-SEM; range, 36.0-84.3 microg/mL; n=92) in healthy Japanese men, and 49.3+/-0.5 microg/mL (34.5-72.8; n=241) in healthy Japanese women. Multiple regression of these data and results from 67 men with CHD showed that apo J concentration was unrelated to age, sex or body mass index, but was positively related to serum PON1 (p<0.001) and apo B (p<0.02) concentrations. In women, it was also positively related to blood glucose (p<0.02). After adjusting for its associations with covariates, serum apo J averaged 5.4 microg/mL, lower in CHD men than in controls (p<0.003). Type 2 diabetics had higher apo J concentrations (men, 83.1+/-3.4 microg/mL, n=64; women, 64.0+/-2.3 microg/mL, n=46) than healthy men and women (p<0.001). In these Type 2 diabetics, apo J concentration was unrelated to PON1 concentration, but was positively related to blood glucose (p<0.01). After adjustment for its relation to blood glucose, the mean apo J concentration was similar in diabetics and healthy subjects. These findings suggest that apo J may be anti-atherogenic in humans, and that its concentration is raised by Type 2 diabetes.


[Quality Indicators of Primary Health Care Facilities in Austria].
The strengthening of primary health care is one major goal of the current national health reform in Austria. In this context, a new interdisciplinary concept was developed in 2014 that defines structures and requirements for future primary health care facilities. The aim of this project was the development of quality indicators for the evaluation of the scheduled primary health care facilities in Austria, which are in accordance with the new Austrian concept. We used the RAND/NPCRDC method for the development and selection of the quality indicators. We conducted systematic literature searches for existing measures in international databases for quality indicators as well as in bibliographic databases. All retrieved measures were evaluated and rated by an expert panel in a 2-step process regarding relevance and feasibility. Overall, the literature searches yielded 281 potentially relevant quality indicators, which were summarized to 65 different quality measures for primary health care. Out of these, the panel rated and accepted 30 measures as relevant and feasible for use in Austria. Five of these indicators were structure measures, 14 were process measures and the remaining 11 were outcome measures. Based on the Austrian primary health care concept, the final set of quality indicators was grouped in the 5 following domains: Access to primary health care (5), quality of care (15), continuity of care (5), coordination of care (4), and safety (1). This set of quality measures largely covers the four defined functions of primary health care. It enables standardized evaluation of primary health care facilities in Austria regarding the implementation of the Austrian primary health care concept as well as improvement in healthcare of the population.


Induction of cytochrome P450 3A by retinoids in rat hepatocyte culture.
1. Rat hepatocytes cultured on a Matrigel matrix were exposed for 48 h to all-trans-retinoic acid, 9-cis-retinoic acid, 13-cis-retinoic acid or fenretinide. 2. Cytochrome P450 3A (CYP3A) RNA levels were increased by approximately eightfold in hepatocytes treated with the retinoids compared to control cultures. 3. CYP1A1 and CYP1A2 RNA levels were only slightly affected or unaffected by the retinoids. 4. The induction of CYP3A by these therapeutically-useful retinoids suggests that they may share a common mechanism for accelerated drug catabolism and acquired clinical resistance.


Withdrawing method of the stiffening tube incidentally inserted into the descending colon.
We experienced a very rare complication of colonoscopy, a migration of stiffening tube into the colorectum. We herein introduce a withdrawing method of migrating stiffening tube incidentally inserted into the colorectum. A 65-year-old Japanese woman underwent colonoscopy because of abdominal discomfort. We used stiffening tube to insert the scope to the proximal colon because of her redundant sigmoid colon. When withdrawing the scope, we realized that the tube was fully inside the colorectum. We could not remove the tube instantly, and it reached the splenic flexure, finally. We reinserted the scope through the migrating tube, straightened the scope, and withdrew it holding a slight angle of the scope over the proximal end of the tube. Then, we could safely remove the tube along with the scope through the anus.


Stress responses in the opportunistic pathogen Acinetobacter baumannii.
Acinetobacter baumannii causes a wide range of severe infections among compromised and injured patients worldwide. The relevance of these infections are, in part, due to the ability of this pathogen to sense and react to environmental and host stress signals, allowing it to persist and disseminate in medical settings and the human host. This review summarizes current knowledge on the roles that environmental and cellular stressors play in the ability of A. baumannii to resist nutrient deprivation, oxidative and nitrosative injury, and even the presence of the commonly used antiseptic ethanol, which could serve as a nutrient- and virulence-enhancing signal rather than just being a convenient disinfectant. Emerging experimental evidence supports the role of some of these responses in the pathogenesis of the infections A. baumannii causes in humans and its capacity to resist antibiotics and host response effectors.


The optimised CO-rebreathing method: a new tool to determine total haemoglobin mass routinely.
A routine method to determine total haemoglobin mass (tHb) in clinical practice and sports medicine is non-existent. Radioactive tracers or other dilution procedures like the common CO-rebreathing method (Proc(com)) are impractical, the latter in particular because of the relatively long time of respiration. According to the multicompartment model of Bruce and Bruce (J Appl Physiol 95:1235-1247, 2003) the respiration time can be considerably reduced by inhaling a CO-bolus instead of the commonly used gas mixture. The aim of this study was to evaluate this theoretical concept in practice. The kinetics of the HbCO formation were compared in arterialised blood sampled from an hyperaemic earlobe after inhaling a CO-bolus (Proc(new)) for 2 min and a CO-O(2) mixture (Proc(com)) for approximately 10 min. The reliability of Proc(new) was checked in three consecutive tests, and phlebotomy was used to determine the validity. VO(2max) was determined with and without previous application of Proc(new) and the half-time of HbCO was registered also in arterialised blood after resting quietly and after the VO(2max) test. Proc(new) yielded virtual identical tHb values compared to Proc(com) when HbCO determined 5 min after starting CO-rebreathing was used for calculation. The typical error of Proc(new) was 1.7%, corresponding to a limit of agreement (95%) of 3.3%. The loss of 95 g (19) haemoglobin was detected with an accuracy of 9 g (12). After application of Proc(new) VO(2max) was reduced by 3.0% (3.7) (P=0.022) and half-time was lowered from 132 min (77) to 89 min (23) after the VO(2max) test. Inhaling a CO-bolus markedly simplifies the CO-rebreathing method without reducing validity and reliability and can be used for routine determination of tHb for various indications.


Functional ovarian reserve in transgender men receiving testosterone therapy: evidence for preserved anti-Müllerian hormone and antral follicle count under prolonged treatment.
Is the functional ovarian reserve in transgender men affected by testosterone therapy? Serum anti-Müllerian Hormone (AMH) levels slightly decrease during testosterone treatment but remain within the normal range, suggesting preserved follicular ovarian reserve. Few small studies have investigated the impact of gender-affirming treatment on reproduction in transgender men. Conflicting results were reached concerning ovarian morphology and AMH levels in this context. The study consisted of two arms. The first arm was a prospective pilot study, which enrolled 56 transgender men (median age 22.5 [interquartile range (IQR)-19-27.7] years), 27 of whom had polycystic ovary syndrome (PCOS), prior to the initiation of gender-affirming testosterone therapy. A structured assessment was conducted prior to, and at 3 and 12 months after treatment initiation. The second arm was a cross-sectional study that comprised 47 transgender men (median age 24 [IQR-20-31] years) who received testosterone for a median duration of 35 [IQR 13-62] months. The main outcome measures were serum AMH and antral follicle count (AFC) as indices of ovarian follicular reserve. The study was conducted at a tertiary center for transgender health. Gender-affirming therapy was administered according to standard practice. AFC was determined by pelvic (abdominal or transvaginal) ultrasound and blood collection for measurements of AMH, testosterone, estradiol, LH and FSH was performed at the designated time-points. Prospective arm for the entire group we observed a decrease of 0.71 ng/ml in AMH levels between baseline and 12 months (P = 0.01). When expressed in age-specific percentiles, AMH went from the 47.37th to the 40.25th percentile at 12 months (P < 0.001). In a sub-group analysis, a decline of 9.52 points in age-specific percentile was seen in subjects with PCOS (P < 0.001), while no changes were detected in the non-PCOS group. Testosterone treatment did not affect AFC over time in the entire cohort. In the sub-group analysis, a mean decrease of 5.0 follicles was detected between baseline and the 12 months assessment (P = 0.047) only in subjects with PCOS. In the cross-sectional study, AMH inversely correlated with age but not with treatment duration. Notably AMH did not deviate from the 50th age-specific percentile. Finally, four men fathered biological children after being under testosterone treatment for up to 12 years. The limited sample size of the pilot study should be kept in mind. An additional limitation is the lack of a control group in the prospective study, as each participant served as his own control. Also, roughly 40% of the ultrasound examinations were performed transabdominally, potentially affecting the accuracy of the AFC measurements.As study participants were quite young, our reassuring data may not apply to older transgender men, either because of an age-related decline in ovarian reserve or to possible long-term effects of testosterone therapy. Furthermore, the chances for fertility preservation may be more limited in subjects with PCOS. This is an additional contribution to the emerging evidence that prolonged testosterone treatment may not be a major obstacle to later fertility potential in transgender men desirous of having children. Larger confirmatory studies, and particularly more with reproductive outcome data, are needed for evidence-based fertility counseling prior to treatment initiation in these subjects. This study received no funding. The authors have no competing interests to declare. N/A.


The prevalence of enduring postnatal perineal morbidity and its relationship to perineal trauma.
to investigate the prevalence of enduring postnatal perineal morbidity and its relationship to perineal trauma. a retrospective cross-sectional community survey of postnatal women. a total population sample of 2100 women were surveyed from two maternity units within Birmingham. Women were identified from the Trust's computerised Maternity Information System (MIS). Women were surveyed using a self-administered postal questionnaire 12 months after birth. The questionnaire included self-assessment of perineal pain, perineal healing, urinary incontinence, flatus incontinence, faecal incontinence, sexual morbidity and dyspareunia. a response rate of 23.3% was achieved (n=482). A high level of perineal morbidity was reported (53.8% stress urinary incontinence, 36.6% urge urinary incontinence, 9.9% liquid faecal incontinence, 54.5% with at least one index of sexual morbidity). Women with perineal trauma reported significantly more morbidity (sexual morbidity, dyspareunia, stress and urge urinary incontinence) than women with an intact perineum. Women with perineal trauma also resumed sexual intercourse later than women with an intact perineum. Women with a first- or second-degree tear reported significantly more perineal morbidity (stress incontinence, sexual morbidity) than women with an intact perineum, and resumed sexual intercourse later. However, a high percentage of women with an intact perineum also reported new-onset perineal morbidity: stress urinary incontinence (34.8%); urge urinary incontinence (19.5%); flatus incontinence (13.8%); and dyspareunia (25.3%), highlighting that enduring perineal morbidity can occur irrespective of perineal trauma. enduring postnatal perineal morbidity is common in women with all types and grades of perineal trauma and intact perineum after childbirth. This highlights the need for further debate and research into the prevalence and experience of postnatal morbidity.


Measurement of nasal irritant sensitivity to pulsed carbon dioxide: a pilot study.
Nasal irritation and associated symptoms (e.g., nasal congestion, rhinorrhea, sinus headache) are important air-pollution-related health complaints, particularly in so-called problem buildings. Individual differences in nasal irritant sensitivity are therefore of both clinical and regulatory interest. To document such differences, one must first functionally define perceptual acuity to airborne irritants. In an adaptation of an established sensory testing method, the authors used the odorless irritant carbon dioxide in an electronically controlled dilution apparatus to deliver brief (approximately 3 s) pulses at controlled levels (10%-70%, vol/vol), synchronized with the inspiratory phase of the respiratory cycle. Investigators who use this apparatus can use a variant of the forced-choice paradigm for threshold determination to document nasal irritant sensitivity. The authors recruited 30 adult volunteers (17 males, 13 females; average age = 41 y, range = 19-79 y) from a university laboratory complex and from the general community. Within this group, there was a skewed distribution of carbon dioxide thresholds (arithmetic mean = 28%, geometric mean = 27% [vol/vol]). In univariate analyses, geometric mean carbon dioxide thresholds differed significantly with respect to smoking status (36% carbon dioxide in smokers versus 25% in nonsmokers; p < .005), but not with respect to age, gender, or self-reported history of allergic rhinitis. In a multivariate analysis, gender also approached significance; females tended to show better perceptual acuity than males (p = .06). Neither self-reported "vasomotor rhinitis" symptoms nor self-reported symptomatic reactivity to environmental tobacco smoke predicted carbon dioxide thresholds. Pulsed carbon dioxide is well tolerated by subjects who participate in a threshold detection task; the procedure yields a potential endpoint with which to compare individuals (and groups) with respect to nasal irritant perceptual acuity. The relationship between such acuity and nasal physiologic reactivity-as well as the generalizability of such measures to other, more environmentally realistic irritants-has yet to be defined.


[Sarcoidosis and primary biliary cholangitis in a patient with cholestasis].
Primary biliary cholangitis and sarcoidosis are both cholestatic liver diseases. Currently, there are no established specific criteria for distinguishing the diseases from each other; diagnosis is based on the anamnesis, as well as the results of physical, laboratory and instrumental examination. The case report presents a female patient with a rare combination of histologically verified liver sarcoidosis and primary biliary cholangitis. Despite the similar clinical manifestations, the approaches to the treatment of these diseases are completely different, that underlines the importance of the differential diagnosis to exclude combined liver damage.


Occurrence of Dirofilaria repens in wild carnivores in Poland.
Dirofilaria repens is an expanding vector-borne zoonotic parasite of canines and other carnivores. Sub-clinically infected dogs constitute the most important reservoir of the parasite and the source of infection for its mosquito vectors. However, occurrence of D. repens infection in wild animals may contribute to the transmission of the parasite to humans and may explain the endemicity of filariae in newly invaded regions. The aim of the current study was to determine the occurrence of D. repens in 511 blood and spleen samples from seven species of wild carnivores (wolves, red foxes, Eurasian badgers, raccoons, raccoon dogs, stone martens, and pine martens) from different regions of Poland by means of a PCR protocol targeting the 12S rDNA gene. Dirofilaria repens-positive hosts were identified in seven of fourteen voivodeships in four of the seven regions of Poland: Masovia, Lesser Poland, Pomerania and Warmia-Masuria. The highest prevalence was found in Masovia region (8%), coinciding with the highest previously recorded prevalence in dogs in Central Poland. The DNA of Dirofilaria was detected in 16 samples of three species (total prevalence 3.13%). A low and similar percentage of positive samples (1.9%, 4.2% and 4.8%) was recorded among badgers, red foxes, and wolves, respectively. Dirofilaria repens-positive hosts were identified in seven of fourteen voivodships. Based on detection in different voivodeships, D. repens-positive animals were recorded in four out of the seven regions of Poland: in Masovia, Lesser Poland, Pomerania, and Warmia-Masuria. The highest prevalence of filariae was found in Masovia region (8%), reflecting the highest previously recorded prevalence in dogs (12-50%) in Central Poland. In summary, we conducted the first comprehensive study on the epidemiology of D. repens in seven species of wild hosts in all seven regions of Poland and identified the first case of D. repens infection in Eurasian badgers in Poland and the second in Europe.


Smart X-ray beam position monitor system using artificial-intelligence methods for the Advanced Photon Source insertion-device beamlines.
At the Advanced Photon Source (APS), each insertion-device (ID) beamline front end has two X-ray beam position monitors (XBPMs) to monitor the X-ray beam position for both vertical and horizontal directions. Performance challenges for a conventional photoemission-type XBPM during operations are contamination of the signal from the neighbouring bending-magnet sources and the sensitivity of the XBPM to the insertion-device gap variations. Problems are exacerbated because users change the ID gap during their operations, and hence the percentage level of the contamination in the front-end XBPM signals varies. A smart XBPM system with a high-speed digital signal processor has been built at the Advanced Photon Source for the ID beamline front ends. The new version of the software, which uses an artificial-intelligence method, provides a self-learning and self-calibration capability to the smart XBPM system. The structure of and recent test results with the system are presented in this paper.


Improvement of sensory impairment in patients with peripheral neuropathy.
To report the findings in 27 patients with peripheral neuropathy (21 with lower extremity sensory impairment associated with diabetic peripheral neuropathy and 6 with other causes), who received treatment with monochromatic near-infrared photoenergy (890 nm) delivered by the Anodyne Therapy System (ATS). All enrolled patients exhibited abnormal sensory perception (either hyperesthesia or hypoesthesia) based on a qualifying examination with the Neurometer CPT (current perception threshold) (baseline CPT). The patients received 10 ATS treatments (each lasting 40 minutes) during a 2-week period and then underwent CPT retesting to determine the extent of improvement of sensory impairment in myelinated and unmyelinated sensory fibers of the peroneal nerve. All patients obtained improvement in sensory impairment in comparison with baseline CPT measures, and 16 of the 27 patients achieved normal sensory responses in all nerve fiber subpopulations. Ten patients had been tested previously (initial CPT) and did not exhibit spontaneous improvement in sensory impairment during a mean period of 27 months before baseline CPT. After receiving the ATS treatments, however, this group of patients showed improvement in comparison with both initial CPT results and baseline CPT. On the basis of the data from this study, the ATS seems to be a safe and effective treatment to improve sensory impairment associated with peripheral neuropathy due to diabetes and other causes.


Effect of calbindin-D28K on cyclosporine toxicity in cultured renal proximal tubular cells.
Cyclosporine A (CsA) is known to have direct toxicity to renal tubular cells. Its toxicity may be mediated by intracellular calcium because CsA increases intracellular calcium concentration and enhances the activities of calcium-dependent calpains and caspases. Calbindin-D28k, a cytosolic calcium binding protein, has been used as an intracellular Ca2+ buffer to reduce calcium-mediated cytotoxicity in non-renal cells such as neuronal cells. We investigated the effects of gene transfer of calbindin-D28k cDNA on CsA cytotoxicity and intracellular calcium concentration ([Ca2+]i) in cultured murine proximal tubular (MCT) cells. A plasmid containing calbindin-D28k cDNA under the control of CMV promoter was transfected to MCT cells with liposomes. Cytotoxicity was assessed by LDH release and cell viability assay, and [Ca2+]i was measured ratiometrically with fura-2. Compared with MCT cells, cells transfected with calbindin-D28k cDNA showed a reduction in LDH release by 27, 30, 32, 33, and 19% (all P < 0.05), respectively, after 24 h exposure to 1, 2.5, 5, 10, and 25 microM CsA. Cell viability after CsA treatment was also significantly higher in CB cells. A mock transfection using plasmid without calbindin-D28k cDNA insert did not affect the LDH release or cell viability after CsA treatment. CsA treatment did not affect the protein and mRNA abundance of transfected calbindin-D28k cDNA. The expression of calbindin-D28k did not affect the baseline [Ca2+]i, but significantly suppressed CsA-induced elevation in [Ca2+]i. The expression of calbindin-D28k in renal tubular cells provides cytoprotective effects against CsA toxicity, probably through its buffering effects on [Ca2+]i.


To compare the outcome (early) of neonates with birth asphyxia in-relation to place of delivery and age at time of admission.
To determine the frequency of birth asphyxia and short-term (early) outcome in relation to age at admission and place of delivery. A descriptive cross-sectional study was conducted in the Paediatric Department, Neonatal Ward of Liaquat University Hospital (LUH) Hyderabad from January to December 2009. All babies were received at our nursery or delivered in LUH with birth asphyxia were included, while babies having major congenital abnormalities, with birth weight < 1800 gm or preterm were excluded. After consent and enrollment their detailed history including peri-natal history, Apgar score, resuscitation measures, problems and outcome were recorded on a pre-designed study proforma. Short-term outcome was measured after 7 hours as clinically improved, developed neurological disability (Hypoxic Ischaemic Encephalopathy stage II or III) or death. The frequency was (n = 600; 25%) of LUMHS born and (n = 310; 61.63%) were received within 6 hours, (n = 272 45% were LUMHS born and n = 7 7% were out born), (n = 37; 38.95%) within 24 hours and (n = 9; 10.3%) after 24 hours. On initial neurological evaluation (n = 90; 15%) were normal while clinical signs of HIE were present in 85%, with (n = 180; 30%) in stage I, (n = 210; 35%) in Stage II and (n = 120; 20%) in stage III of HIE. Outcome was measured after 72 hours, around 53.3% (320) were normal, 31.6% (190) developed neurological disability, while 15% (90) babies expired. Outcome was better in Liaquat University of Medical Health Sciences (LUMHS) born than out-born with statistically significant difference in terms of disability (Chi-square test P-value < 0.0001) but no difference was noted in terms of disability to death. There was a statistically improved outcome for babies received within 6 hours than those after 6 hours of birth (Chi-square test P-value < 0.0255). Early recognition of birth asphyxia and timely referral to tertiary center can reduce morbidity and mortality.


Institution based tumor registry from Punjab: five year data based analysis.
There are no population based cancer registries in Pakistan except for Karachi Cancer Registry (KCR). No data from Punjab is available in the last decade. We decided to conduct a data base analysis to see the frequencies of different cancers in Punjab. A retrospective analysis of 5100 patients presenting to Jinnah Hospital between January 1997 to December 2001 with histological diagnosis of cancer was performed. A tumor registry performa on all patients was filled which included demographic data as age, sex, duration of symptoms and disease stage at presentation. All cancers were coded according to international classification of Disease-oncology (ICD-10) classification. Male cancers accounted for 47.7% and female cancers 52.2% of the total cases. In males the three most frequent cancers were leukemias, non-Hodgkins lymphoma and lung cancer. In females breast cancer was the most common cancer accounting for 38.5% female followed by ovarian cancer 13.6%. Our institution based cancer registry indicates hematological malignancies are the most common cancers in males in Punjab followed by lung and colorectal cancer. In females breast cancer is the commonest cancer followed by ovarian cancer. Gall bladder cancer is relatively more frequent in women while cervical cancer is less commonly observed in our patient population. Despite biases until population based incidences are available, studies like ours may prove beneficial for future health planning and research.


Study of Terpenoid Synthesis and Prenyltransferase in Roots of Rehmannia glutinosa Based on iTRAQ Quantitative Proteomics.
Rehmannia glutinosa has important medicinal value; terpenoid is one of the main active components in R. glutinosa. In this study, iTRAQ technique was used to analyze the relative abundance of proteins in roots of R. glutinosa, and 6,752 reliable proteins were quantified. GO enrichment results indicated that most proteins were involved in metabolic process or cellular process, 57.63% proteins had catalytic activity, and 65.80% proteins were enriched in membrane-bounded organelle. In roots of R. glutinosa, there were 38 KEGG enrichments with significance, more DEPs were found in some pathways, especially the proteasome pathway and TCA cycle with 15.0% DEPs between elongation stage and expansion stage of roots. Furthermore, five KEGG pathways of terpenoid synthesis were found. Most prenyltransferases belong to FPP/GGPP synthase family, involved in terpenoid backbone biosynthesis, and all interacted with biotin carboxylase CAC2. Compared with that at the elongation stage, many prenyltransferases exhibited higher expression at the expansion stage or maturation stage of roots. In addition, eight FPP/GGPP synthase encoding genes were cloned from R. glutinosa, namely FPPS, FPPS1, GGPS, GGPS3, GGPS4, GGPS5, GPPS and GPPS2, introns were also found in FPPS, FPPS1, GGPS5 and GGPS2, and FPP/GPP synthases were more conservative in organisms, especially in viridiplantae, in which the co-occurrence of GPPS or GPPS2 was significantly higher in plants. Further analysis found that FPP/GGPP synthases of R. glutinosa were divided into three kinds, GGPS, GPPS and FPPS, and their gene expression was significantly diverse in different varieties, growth periods, or tissues of R. glutinosa. Compared with that of GGPS, the expression of GPPS and FPPS was much higher in R. glutinosa, especially at the expansion stage and maturation stage. Thus, the synthesis of terpenoids in roots of R. glutinosa is intricately regulated and needs to be further studied.


Somatic presentations of psychiatric illness in primary care setting.
We have tried to describe somatisation, not as a disease, but as a common and important human mechanism involving both doctor and patient. It is the single most common reason why psychiatric illness goes undetected in general medical settings, and it often occurs in conjunction with physical disease processes. The association with dysphoric affect has been recognised at least since George Cheyne 250 years ago, and the reason for this is that both anxiety and depression serve to amplify pains. However, it seems likely that somatisation can occur in the absence of dysphoria. Once it has been established, it is easy to see how it continues: it secures advantages from spouse, family and employers; and it tends to be encouraged by doctors--who differentially reward somatic symptoms. But why does it occur in the first place? We have argued that it seems to have three functions: First, it allows people who are unsympathetic to psychological illness, or who live in cultures where mental illness is stigmatised, to nonetheless occupy the sick-role while psychologically unwell. Second, it is blame-avoiding: instead of being responsible for the mayhem, one is cast in the role of the suffering victim. Finally, by reducing blame, it appears to save patients from being as depressed as they might otherwise have been.


The substance of a support group.
This ethnographic research constitutes a study of the culture of a family-run advocacy organization for families of children and youth with mental health needs. Data collection includes 703 pages of interview transcripts, observations, field notes, and archival material collected by the principle investigator during 2.5 years of participant observation with this support group. This article provides the context for the study and describes the support group's cultural ideologies and cultural forms that are a concrete expression of those ideologies: There are four major categories of cultural forms as follows: symbols, language, narratives or stories, and practices. Manifestations of each form are discussed and described. The proliferation of support and advocacy groups in the mental health arena promises a rich source of understanding of the needs of families in distress as well as inspiration for new and practical interventions.


Search for new bottomlike quark pair decays QQ-->(tW(+)(-))(tW(+)(-)in same-charge dilepton events.
We report the most restrictive direct limits on masses of fourth-generation down-type quarks b{'}, and quarklike composite fermions (B or T{5/3}), decaying promptly to tW{-/+}. We search for a significant excess of events with two same-charge leptons (e, mu), several hadronic jets, and missing transverse energy. An analysis of data from pp collisions with an integrated luminosity of 2.7 fb{-1} collected with the CDF II detector at Fermilab yields no evidence for such a signal, setting mass limits m{b{'}}, m{B}>338 GeV/c{2} and m{T{5/3}}>365 GeV/c{2} at 95% confidence level.


Nanopore Electroporation Device for DNA Transfection into Various Spreading and Nonadherent Cell Types.
Cell transfection plays a crucial role in the study of gene function and regulation of gene expression. The existing gene transfection methods, such as chemical carriers, viruses, electroporation, and microinjection, suffer from limitations, including cell type dependence, reliance on cellular endocytosis, low efficiency, safety concerns, and technical complexity. Nanopore-coupled electroporation offers a promising approach to localizing electric fields for efficient cell membrane perforation and nucleic acid transfection. However, the applicability of nanopore electroporation technology across different cell types lacks a systematic investigation. In this study, we explore the potential of nanopore electroporation for transfecting DNA plasmids into various cell types. Our nanopore electroporation device employs track-etched membranes as the core component. We find that nanopore electroporation efficiently transfects adherent cells, including well-spreading epithelial-like HeLa cells, cardiomyocyte-like HL-1 cells, and dendritic-cell-like DC2.4 cells. However, it shows a limited transfection efficiency in weakly spreading macrophages (RAW264.7) and suspension cells (Jurkat). To gain insights into these observations, we develop a COMSOL model, revealing that nanopore electroporation better localizes the electric field on adherent and well-spreading cells, promoting favorable membrane poration conditions. Our findings provide valuable references for advancing nanopore electroporation as a high-throughput, safe, and efficient gene transfection platform.


Real-world effectiveness of azvudine for patients infected with the SARS-CoV-2 omicron subvariant BA.5 in an intensive care unit.
Azvudine (FNC) has been shown to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but data regarding the Omicron BA.5.1.3 subvariant are lacking. This retrospective analysis investigated the effectiveness and safety of FNC against the SARS-CoV-2 Omicron BA.5.1.3 subvariant in a real-world setting, utilizing data from a patient cohort at our institution. Data were retrospectively collected from patients admitted to the intensive care unit (ICU) of Sanya Central Hospital during the Sanya outbreak (August 13 to September 7, 2022). The patients, all infected with the Omicron BA.5.1.3 subvariant, were selected based on predefined inclusion and exclusion criteria. The patients were classified as the FNC (azvudine 5 mg, qd + standard supportive treatment) and non-FNC (standard supportive treatment only) groups. The study comprised 13 patients, with 6 and 7 in the FNC and non-FNC groups, respectively. Baseline data, clinical features, and imaging manifestations were generally similar between the two groups. However, patients administered FNC demonstrated significantly lower levels of inflammatory indicators at baseline. Although there was no significant difference in the duration of ICU stay between the FNC and non-FNC groups, overall ICU stay appeared to be reduced in the FNC group. FNC emerges as a feasible treatment against the Omicron BA.5.1.3 subvariant. It may reduce ICU stay and demonstrate a promising safety profile without major side effects or disruption to normal physiological parameters.


Antifungal activity of amphotericin B conjugated to carbon nanotubes.
Amphotericin B (AMB) has long been considered the most effective drug in the treatment of serious invasive fungal infections. There are, however, major limitations to its use, due to several adverse effects, including acute infusional reactions and, most relevant, a dose-dependent nephrotoxicity. At least some of these effects are attributed to the aggregation of AMB as a result of its poor water solubility. To overcome this problem, reformulated versions of the drug have been developed, including a micellar dispersion of AMB with sodium deoxycholate (AMBD), its encapsulation into liposomes, or its incorporation into lipidic complexes. The development of nanobiotechnologies provides novel potential drug delivery systems that make use of nanomaterials such as functionalized carbon nanotubes (f-CNTs), which are emerging as an innovative and efficient tool for the transport and cellular translocation of therapeutic molecules. In this study, we prepared two conjugates between f-CNTs and AMB. The antifungal activity of these conjugates was tested against a collection of reference and clinical fungal strains, in comparison to that of AMB alone or AMBD. Measured minimum inhibition concentration (MIC) values for f-CNT-AMB conjugates were either comparable to or better than those displayed by AMB and AMBD. Furthermore, AMBD-resistant Candida strains were found to be susceptible to f-CNT-AMB 1. Additional studies, aimed at understanding the mechanism of action of the conjugates, suggest a nonlytic mechanism, since the compounds show a major permeabilizing effect on the tested fungal strains only after extended incubation. Interestingly, the f-CNT-AMB 1 does not show any significant toxic effect on Jurkat cells at antifungal concentrations.


OCCURRENCE OF NUCLEOTIDES IN CULTURE FLUIDS OF MICROORGANISMS. V. EXCRETION OF ADENOSINE CYCLIC 3',5'-PHOSPHATE BY BREVIBACTERIUM LIQUEFACIENS SP. N.
Okabayashi, Tadashi (Shionogi & Co., Ltd., Fukushima-ku, Osaka, Japan), Akihiro Yoshimoto, and Misao Ide. Occurrence of nucleotides in culture fluids of microorganisms. V. Excretion of adenosine cyclic 3',5'-phosphate by Brevibacterium liquefaciens sp. n. J. Bacteriol. 86:930-936. 1963.-Brevibacterium liquefaciens sp. n., when grown in a medium containing amino acids as the nitrogen source, excreted a considerable amount of an adenine ribonucleotide, which had not previously been noticed. The nucleotide was identified as adenosine cyclic 3',5'-phosphate by analysis, ultraviolet-absorption spectra, infrared-absorption spectra, paper chromatography, paper electrophoresis, and by comparison of behavior in hydrolysis by HCl, NaOH, and Ba(OH)(2); also, behavior in digestion with a crude enzyme preparation of adenosine cyclic 3',5'-phosphate phosphodiesterase was compared with that of an authentic sample. Preliminary examination of culture conditions revealed that, at least superficially, the substitution of dl-alanine for Casamino Acids (as nitrogen source) is one of the causes of the excretion of adenosine cyclic 3',5'-phosphate.


A Machine Learning Paradigm for Studying Pictorial Realism: How Accurate are Constable's Clouds?
The British landscape painter John Constable is considered foundational for the Realist movement in 19th-century European painting. Constable's painted skies, in particular, were seen as remarkably accurate by his contemporaries, an impression shared by many viewers today. Yet, assessing the accuracy of realist paintings like Constable's is subjective or intuitive, even for professional art historians, making it difficult to say with certainty what set Constable's skies apart from those of his contemporaries. Our goal is to contribute to a more objective understanding of Constable's realism. We propose a new machine-learning-based paradigm for studying pictorial realism in an explainable way. Our framework assesses realism by measuring the similarity between clouds painted by artists noted for their skies, like Constable, and photographs of clouds. The experimental results of cloud classification show that Constable approximates more consistently than his contemporaries the formal features of actual clouds in his paintings. The study, as a novel interdisciplinary approach that combines computer vision and machine learning, meteorology, and art history, is a springboard for broader and deeper analyses of pictorial realism.


Lateral semi-circular canal asymmetry in females with idiopathic scoliosis.
Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal structural deformity that occurs in otherwise normal individuals. Although curve progression and severity vary amongst individuals, AIS can lead to significant cosmetic and functional deformity. AIS etiology has been determined to be genetic, however, exact genetic and biological processes underlying this disorder remain unknown. Vestibular structure and function have potentially been related to the etiopathogenesis of AIS. Here, we aimed to characterize the anatomy of the semicircular canals (SCC) within the vestibular system through a novel approach utilizing T2-weighted magnetic resonance images (MRI). Three dimensional, MRI-based models of the SCCs were generated from AIS subjects (n = 20) and healthy control subjects (n = 19). Linear mixed models were used to compare SCC morphological measurements in the two groups. We compared side-to-side differences in the SCC measurements between groups (group*side interaction). Side-to-side differences in the lateral SCC were different between the two groups [false discovery rate adjusted p-value: 0.0107]. Orientation of right versus left lateral SCC was significantly different in the AIS group compared to the control group [mean side-to-side difference: -4.1°, 95% CI: -6.4° to -1.7°]. Overall, among subjects in the AIS group, the left lateral SCC tended to be oriented in a more horizontal position than subjects in the control group. Asymmetry within the SCCs of the vestibular system of individuals with AIS potentially results in abnormal efferent activity to postural muscles. Consequences of this muscular activity during periods of rapid growth, which often coincides with AIS onset and progression, warrant consideration.


[Ultrasonographic examination of the circulation in the hepatic vein in diffuse liver diseases].
59 patients suffering from diffuse liver lesion and 28 healthy individuals had undergone duplex ultrasound examination of the hepatic vein circulation. Three time-velocity spectra had been noticed and later divided into three groups: 1. Normal (triphasic) spectrum. 2. Decreased and deformed amplitudes. 3. Flat flow spectrum. The control group matched the normal (triphasic) spectrum of type 1 without exception. Type 2 could be observed in steatosis, chronic active hepatitis and cirrhosis alike. The type 3 spectrum was shown significantly, to occur with 71% sensitivity and with 100% specificity in cirrhosis of the liver. The comparison of the results with the circulation velocities measured in the main portal vein showed a sensitivity of 88% and a specificity of 94%. Based on this initial experience, authors hold the view that a technically simple hepatic vein Doppler-sonography can complete the clinical analysis with significant additional information in cases of diffuse liver lesion.


Esculetin Inhibits Adipogenesis and Increases Antioxidant Activity during Adipocyte Differentiation in 3T3-L1 Cells.
This study was conducted to investigate the anti-adipogenic activity of esculetin (ECT) which is reported to be attributable to the modulation of antioxidant enzymes during adipogenesis. After six days of ECT treatment of 3T3-L1 cells, lipid accumulation was determined by Oil red O staining. The levels of glutathione (GSH) and reactive oxygen species (ROS), and the activities of antioxidant enzymes including glutathione reductase, glutathione peroxidase (GPx), and catalase were examined. In addition, the protein expression of glutamate-cysteine ligase catalytic subunit (GCLC) and heme oxygenase-1 (HO-1) was measured by Western blot. ECT significantly inhibited lipid accumulation by approximately 80% and ROS production in a concentration-dependent manner. GSH level and GPx activity were increased by ECT by approximately 1.3-fold and 1.7-fold compared to the control group, respectively. GCLC and HO-1 expression were elevated by ECT. These results showed that ECT treatments strongly inhibit adipogenesis, increase GSH level, and upregulate the expression of GCLC and HO-1, possibly by decreasing ROS production in 3T3-L1 cells during adipogenesis.


Clinical heterogeneity of Pulmonary Arterial Hypertension associated with variants in TBX4.
The knowledge of hereditary predisposition has changed our understanding of Pulmonary Arterial Hypertension. Genetic testing has been widely extended and the application of Pulmonary Arterial Hypertension specific gene panels has allowed its inclusion in the diagnostic workup and increase the diagnostic ratio compared to the traditional sequencing techniques. This is particularly important in the differential diagnosis between Pulmonary Arterial Hypertension and Pulmonary Venoocclusive Disease. Since November 2011, genetic testing is offered to all patients with idiopathic, hereditable and associated forms of Pulmonary Arterial Hypertension or Pulmonary Venoocclusive Disease included in the Spanish Registry of Pulmonary Arterial Hypertension. Herein, we present the clinical phenotype and prognosis of all Pulmonary Arterial Hypertension patients with disease-associated variants in TBX4. Out of 579 adults and 45 children, we found in eight patients from seven families, disease-causing associated variants in TBX4. All adult patients had a moderate-severe reduction in diffusion capacity. However, we observed a wide spectrum of clinical presentations, including Pulmonary Venoocclusive Disease suspicion, interstitial lung disease, pulmonary vascular abnormalities and congenital heart disease. Genetic testing is now essential for a correct diagnosis work-up in Pulmonary Arterial Hypertension. TBX4-associated Pulmonary Arterial Hypertension has marked clinical heterogeneity. In this regard, a genetic study is extremely useful to obtain an accurate diagnosis and provide appropriate management.


[Shoulder pain: image guided management].
Different interventional radiology techniques used in the management of the painful shoulder will be reviewed in this article. The etiology of shoulder pain is variable, and several image guided procedures are available, from simple to more complex. US and fluoroscopy guided intra-articular and bursal infiltration techniques will be described. Percutaneous needle removal of calcific deposits and capsular distension/infiltration of adhesive capsulitis will be discussed. Cysts in the spinoglenoid or suprascapular notch may cause impingement of the suprascapular nerve and may be aspirated under US guidance. Finally, percutaneous radio-frequency treatment of symptomatic bone metastases under CT guidance may at times be performed. Musculoskeletal radiologists should be familiar with this spectrum of image guided interventional procedures.


Effectiveness of superheated steam and gas catalytic infrared heat treatments to inactivate Salmonella on raw almonds.
The majority of the almond-related outbreaks have been associated with Salmonella. Therefore, it is necessary to find an effective method to inactivate these organisms on the raw almond before distribution in the market. This study was conducted to assess the effectiveness of superheated steam (SHS) treatments followed by catalytic infrared (IR) heat treatment to inactivate Salmonella populations on raw almond and to determine the effect of these treatments on the quality of raw almond. It has been found that SHS treatment for 70 seconds followed by catalytic IR heat treatment for 70 seconds was able to reduce 5.73 +/- 0.11 log CFU/g Salmonella population, and no survivors were found in the enrichment medium. The overall visual quality parameters of both treated and nontreated almonds were found within the acceptable limit. Therefore, SHS treatments for 70 seconds followed by catalytic IR heat treatment for 70 seconds could be an effective decontamination method for raw almonds.


Single-mode Bragg ring laser diodes.
We have designed and fabricated a monolithic semiconductor ring laser based on a Bragg waveguide structure. Through careful control of the waveguiding, we have overcome the inherent "leaky" nature of this waveguide mode and demonstrated a ring laser lasing in the Bragg mode. Best behavior was obtained from lasers with a diameter of 400 µm, where they exhibited output power ${ \gt }{1}\;{\rm mW}$>1mW, in continuous wave (CW) operation. A tangent waveguide provided access to the ring cavity using two ports through evanescent coupling. To meet the stringent waveguiding requirements imposed by the Bragg structure, a two-step etching process, consisting of a shallow-etched coupler and a deep-etched bend section of the ring, was developed in order to reduce the bend and scattering losses. The laser showed a threshold current density of ${\sim}{2.2}\;{{\rm kA/cm}^2}$∼2.2kA/cm2 in CW operation with single longitudinal mode operation with a signal-to-noise ratio of 30 dBm obtained at 1.5 ${I_{\rm th}}$Ith. Broadband phase-matching of $\chi ^{(2)}$χ(2) nonlinearity is observed, offering self-pumped parametric C-band conversion ${ \gt }{40}\;{\rm nm}$>40nm with efficiency of ${142}\% \;{{\rm W}^{ - 1}}\;{{\rm cm}^{ - 2}}$142%W-1cm-2.


Histologic and ultrastructural studies of juvenile onset renal disease in four Rottweiler dogs.
Juvenile onset renal disease is described in 2 male and 2 female young Rottweiler dogs. Histologic changes in all dogs were cystic dilatation of Bowman's space, mesangial hypercellularity, and glomerulosclerosis. Three dogs also had glomerular crescents and moderate to severe interstitial fibrosis. Electron microscopy revealed glomerular basement membranes of variable thickness, with extensive splitting or lamellation of the lamina densa. These ultrastructural findings are similar to those found in people and in other breeds of dogs with inherited defects in type IV collagen.


Upper gastrointestinal tract disease and probiotics.
Diseases of the oropharynx, oesophagus, stomach and duodenum are common. This review discusses the microflora of the upper gastrointestinal tract with particular reference to lactic acid bacteria and the effect of acid suppression. Probiotics can survive in these sites and evidence is presented for potential roles in disease prevention and treatment, particularly with regards to peptic ulcer disease, Helicobacter pylori infection and gastric cancer.


[Surgical treatment and outcome of pelvic metastases].
To retrospectively review the different types of surgical procedures for pelvic metastases, especially for periacetabular metastases. Eighty-eight patients with pelvic metastasis received surgical treatment between July 1997 and July 2005. The series included 40 females and 48 males, with an average age of 54 years. The original sites of carcinoma included 23 from breast, 15 from lung, 13 form kidney, 3 from thyroid, 2 from bladder, 3 from prostate, 3 form liver, 7 from gastro intestine, and 3 from gynecological viscera Thirteen cases were diagnosed as unknown primary metastases. Thirty-two patients had solitary metastasis and 56 patients had multiple bone metastases. Eighteen patients had Type I pelvic resections, 50 had type II, and 10 patients had Type III and Type IV each. Surgical treatments included 72 intralesional curettages and 16 en bloc resections. In 29 patients, the bone defect after tumor resection was reconstructed with methyl acrylate alone or combined with Steinmann pins and screw-rod system. Acetabular reconstructions underwent in 50 patients. Local resections with no reconstructions were done in 5 patients, and hemipelvectomy in 4 patients. The mean time of follow-up was 13 months, ranging from 6 to 24 months. Twenty-nine patients were lost follow-up. Postoperative improvements in 86 (97.8%) patients were seen in pain and mobility scores. The average VAS pain scores were 7.2 points preoperatively and 3.5 points postoperatively. Postoperative function was evaluated according to Enneking's criteria, with a mean score of 19.2 points, including 16.4 points for periacetabular lesions and 23.5 for others. Local recurrence was seen in 11 patients, the average recurrence time was 5.6 months after surgery. Surgical complications occurred in 12 patients, including 8 wound complications, 2 multi-organ function failures, 1 pulmonary embolism, and 2 dislocations. The indications of surgical intervention for pelvic metastasis are severe pain and difficulty in ambulation. The surgical objective is alleviation of pain, restore the mobility and stability of the hip. The surgical procedure for most metastases is curettage and cement filling. Wide resection is an alternative method for solitary pelvic metastasis with good prognosis.


Effect of ketotifen on phosphodiesterase activity from asthmatic individuals.
It was demonstrated, in this study, that phosphodiesterase activity was elevated in asthmatic patients compared to healthy individuals. This may be reason why various authors found higher intracellular cAMP levels in healthy individuals than in asthmatic patients. We also demonstrated that the efficacy of ketotifen in inhibiting antigen-specific histamine release is due to the potent inhibitor effect of ketotifen on cellular phosphodiesterase activity which then allowed intracellular cAMP accumulation, and as a consequence prevented mediators release.


Stereochemistry of the [4 + 2] cycloadditions of trans,trans- and cis,trans-2,4-hexadiene to C(60).
The [4 + 2] cycloaddition of trans,trans-2,4-hexadiene with C(60) proceeds via a concerted mechanism with retention of stereochemistry in the cycloadduct 1a. However, when cis,trans-2,4-hexadiene reacts with C(60), isomerization of the cis,trans to the thermodynamically more stable trans,trans isomer occurs. Subsequently, the cis,trans diene isomerized to the trans,trans isomer and cycloadds to C(60), to form adduct 1a. When the reaction is carried out at higher temperatures, the formation of cycloadduct 1b is also obtained. This result is consistent with a concerted cycloaddition of cis,trans-2,4-hexadiene with C(60), which is more reactive at elevated temperatures and leads to the formation of the Diels-Alder adduct 1b.


[Reduction in Patient Waiting Times in Pharmacies by a Protocol to Minimize Inquiries to Doctors under an Agreement between a Hospital and Community Pharmacies].
Cooperative care between hospitals and community pharmacies is important to safe and effective pharmacotherapy for outpatients. We developed a protocol comprising three agreements about alternative drugs and dosing schedules with the aim of minimizing inquiries about prescriptions to doctors. The protocol was implemented under an agreement between core hospitals in Gifu City and community pharmacy members of the Gifu City Pharmaceutical Association from October 2019. Here, we examined the impact of this protocol on patient waiting time in pharmacies. Before introduction of the protocol, median patient waiting time for questionable prescriptions requiring an inquiry to a doctor was significantly longer than that for prescriptions not requiring an inquiry (23.0 min vs. 10.0 min, p<0.001). After introduction of the protocol, median time for prescriptions which were questionable but nevertheless under the protocol did not require an inquiry to a doctor was significantly reduced compared with those which were questionable and still did require an inquiry (15.0 min vs. 24.0 min, p=0.038). In conclusion, introduction of a protocol aimed at minimizing inquiries about prescriptions to doctors from a community pharmacy was useful in reducing the waiting time of patients, and also likely in decreasing the working times of medical doctors and pharmacists.


Aminomalonic acid: identification in Escherichia coli and atherosclerotic plaque.
Aminomalonic acid (Ama) has been isolated from proteins of Escherichia coli and human atherosclerotic plaque. The presence of Ama has important biological implications because the malonic acid moiety potentially imparts calcium binding properties to protein. Ama was obtained by anaerobic alkaline hydrolysis and identified by chromatographic behavior, quantitative acid-mediated decarboxylation to glycine, and unambiguous gas chromatographic/mass spectral detection. The chromatographic, chemical, and mass spectral properties of naturally occurring Ama were identical to those of the synthetic compound. Amino acid analysis and GC/mass spectrometry also revealed the presence of beta-carboxyaspartic acid and gamma-carboxyglutamic acid in the base hydrolysate of human atherosclerotic plaque. The ratio of Ama to beta-carboxyaspartic acid to gamma-carboxyglutamic acid was 20:1:10, and the quantity of Ama per 1,000 glycine residues was 0.2. Ama is a relatively unstable, minor amino acid in complex structures such as bacteria or tissues. This may explain why it has escaped detection previously, despite intensive investigation.


Differential impacts of wildfire on the population dynamics of an old-forest species.
Ecological disturbances shape and maintain natural communities, but climate change and human land use can alter disturbance regimes and affect population persistence and vital rates in unpredictable ways. Species inhabiting landscapes shaped by wildfire have evolved mechanisms allowing them to persist under this dynamic disturbance type, which creates habitats of varying quality for these species. We utilized data from a 26-yr demographic study of northern spotted owls to analyze the influence of wildfire on apparent survival and recruitment rates. Wildfires occurred across different years and affected different spotted owl territories, which allowed us to implement a retrospective Before-After-Control-Impact (BACI) analysis and model the potential effect of wildfire extent and severity. Our results indicated that mixed-severity fires that burned at predominantly low-severity had little effect on survival and recruitment while fires characterized by more medium to high burn severities negatively affected spotted owl survival, with varying effects on recruitment. Reduced survival and increased recruitment rates on some territories affected by medium to high severity fires suggested that post-fire habitat quality was reduced resulting in territories that were marginally capable of supporting owls. We hypothesize these territories may have represented "sinks" that were supported by nearby "source" territories in a spatially heterogeneous landscape created by the mixed-severity fire regime of the region.


[Fisher's syndrome].
The authors describe a 43-year-old man with ophthalmoplegia, ataxia and areflexia and with 0.42 g/l of protein in the cerebrospinal fluid. EMG disclosed some slowing down of the conduction velocity in the motor fibres of the extremities. Treatment with synacthen depot, cocarboxylase and vitamins gave a good effect. The described case corresponds closely to Fisher's syndrome and may be a special form of brain-stem encephalitis involving the mesencephalon.


Contingency and contiguity of imitative behaviour affect social affiliation.
Actions of others automatically prime similar responses in an agent's behavioural repertoire. As a consequence, perceived or anticipated imitation facilitates own action control and, at the same time, imitation boosts social affiliation and rapport with others. It has previously been suggested that basic mechanisms of associative learning can account for behavioural effects of imitation, whereas a possible role of associative learning for affiliative processes is poorly understood at present. Therefore, this study examined whether contingency and contiguity, the principles of associative learning, affect also the social effects of imitation. Two experiments yielded evidence in favour of this hypothesis by showing more social affiliation in conditions with high contingency (as compared to low contingency) and in conditions of high contiguity (compared to low contiguity).


A Phase 1 study evaluating AMG 337 in Asian patients with advanced solid tumors.
AMG 337, a selective small-molecule MET inhibitor, was evaluated in Asian patients with advanced solid tumors. Eligible patients orally self-administered AMG 337; the initial dose of 150 mg once daily (QD) was escalated to 300 mg QD (modified 3+3+3 design). Treatment continued until disease progression, intolerability, or death. The primary endpoint was adverse events (AEs) and clinical abnormalities defined as dose-limiting toxicities (DLTs). Secondary endpoints included other AEs, pharmacokinetics and tumor response. Eleven patients were enrolled. No DLTs occurred. The most common treatment-emergent AEs were headache (73%) and nausea (45%). Cmax and AUC0-24 exposures increased proportionally with dose; t1/2 was comparable between groups; plasma accumulation was minimal over 28 days. One patient (150 mg) had partial response; one patient (300 mg) had stable disease. Safety, tolerability, pharmacokinetics and efficacy of AMG 337 in Asian patients were consistent with those observed in Western patient populations. The study was terminated early.


Counselors' adjective correlates of working alliance.
The authors present a study of 85 counselors' adjective descriptors of clients in relation to a working alliance. The imperative for such a study emerges from Cough's 1965 Conceptual Analysis of Test Scores approach to clinical measurement. For this investigation, all 300 items of the Adjective Check List were used. Working alliance was measured by the counselor's form of the Working Alliance Inventory-Short. Point biserial correlation of each adjective with inventory scores produced 54 significant adjectives. These 54 adjectives were 18 times the number expected by chance.


Decrease of intracellular ROS by arbutin is associated with apoptosis induction and downregulation of IL-1β and TNF-α in LNCaP; prostate cancer.
Increased reactive oxygen species (ROS) along with inflammation are involved in the prostate cancer (PCa). Therefore, this study was conducted to investigate the molecular mechanisms that were affected by arbutin as an antioxidant on prostate cancer cell line; LNCap. The intracellular ROS measurement confirmed that arbutin significantly (p < .05) decreased the ROS levels in a dose-dependent manner. Detection of cell death profile established that 1,000 μM of arbutin could remarkably induced apoptosis (p < .05), while tert-butyl hydroperoxide (tBHP) as ROS inducer prompted necrosis. In addition, 1,000 µM of arbutin successfully decreased expressions of IL-1β and TNF-α genes (p < .05). Furthermore, evaluation of the IL-1β protein level showed that arbutin could significantly decrease this cytokine (p < .05). In summary, reduction of ROS along with increasing apoptosis and decreasing expression of pro-inflammatory genes following arbutin treatment can open new visions in the treatment of prostate cancer using complementary medicine. PRACTICAL APPLICATIONS: Nowadays, arbutin as a glycosylated hydroquinone is available commercially in both natural and synthetic forms. Arbutin is of interest because of its skin-lightening effect, and used in cosmetic products for cutaneous hyperpigmentation. Arbutin inhibited tyrosinase in melanocytes competitively. Moreover, arbutin was able to attenuate oxidative stress and, its anti-inflammatory activities has been established. In addition, arbutin has represented useful activities for suppression of malignant melanoma development. In addition, arbutin exhibits several pharmacological effects, including antimicrobial, antihyperlipidemic, antihyperglycemic, and alpha amylase inhibitory effects. In this study, we showed its effect on prostate cancer in vitro. Therefore, it opens new insights in the complementary medicine that can maintain or improve human health.


Integrated analysis of gut and oral microbiome in men who have sex with men with HIV Infection.
Human immunodeficiency virus (HIV) infection leads to severe deficiency in host immunity by depletion of CD4+ T-cells, resulting in an imbalance between the human microbiome and host immune response. Alterations in both gut and oral microbiomes have been observed in people living with HIV (PLWH). However, the impact of an altered gut and oral microbiome on HIV disease progression and the relationship between them in PLWH have not been explored. In this longitudinal study, we enrolled acute HIV-infected men who have sex with men (MSM) (n = 15), chronic HIV-infected MSM (n = 15), and HIV-uninfected MSM controls (n = 15). We collected anal and throat swab samples at recruitment (W0) from all participants and at 12 wk after antiretroviral therapy (ART) (W12) from the patients and performed 16S rRNA gene sequencing of genomic DNAs extracted from these swabs. In HIV-infected individuals with CD4 T-cell counts < 350 cells/µL, the increase in abundance of Streptococcus in the oral microbiome was inversely correlated with that of Streptococcus in the gut microbiome (r = -0.490, P = 0.039). In addition, the lower CD4+ T-cell counts (<200 cells/µL) were associated with the higher abundance of Escherichia-Shigella and the lower abundance of Methylobacterium-Methylorubrum of the gut microbiome in HIV-infected individuals. We demonstrate the alteration of gut microbiome resulting from HIV infection and ART and the relationship between the gut and oral microbiome in PLWH and controls. These findings highlight the need for a better understanding of the interactions between the oral and gut microbiome and its potential role in HIV disease progression. IMPORTANCE Our longitudinal integrated study has shown the marked alterations in the gut and oral microbiome resulting from acute and chronic HIV infection and from antiretroviral therapy. Importantly, the relationship between oral and gut microbiomes in people living with acute and chronic HIV infection and "healthy" controls has also been explored. These findings might contribute to a better understanding of the interactions between the oral and gut microbiomes and its potential role in HIV disease progression.


Key proteins and pathways that regulate lifespan.
Here, we review three sets of key proteins and their corresponding downstream pathways that have been linked to extending lifespan and promoting health span in a wide range of organisms. In particular, we review the biology of the sirtuin family of proteins, the insulin/insulin-like growth factor (IGF) signaling (IIS) pathway, and the mechanistic target of rapamycin (mTOR). Using insights derived from simple model organisms, mice, and humans we discuss how these proteins and pathways may potentially alter the rate of aging. We further describe how knowledge of these pathways may lead to the rational design of small molecules that modulate aging and hence alter the propensity for a host of age-related diseases.


Comparison of the efficacy of three different chlorhexidine preparations in decreasing the levels of mutans streptococci in saliva and interdental plaque.
The aim of the present study was to evaluate and compare the effects of three different chlorhexidine (CHX)-containing preparations on mutans streptococci (MS) levels in interdental plaque and whole saliva. Ninety-three healthy school-children (8-10 years old) with high scores of salivary MS were selected by a screening procedure and randomised into three equally sized groups. MS were enumerated at all mesial interdental sites of the first permanent molars with aid of a modified chairside technique. The patients were then treated three times within 2 weeks with either a 1% CHX/thymol-containing varnish (group A) or a 1% CHX gel (group B), or they were subjected to daily supervised toothbrushing with a 0.4% CHX dentifrice for 1 month (group C). Follow-up samples of saliva and plaque from the interdental sites were collected 1 and 3 months after termination of treatment. A statistically significant reduction of MS levels in saliva and interdental plaque was found in all groups after 1 month. The CHX-containing dentifrice (group C) was the most effective method in reducing MS levels in saliva, and a significantly stronger (p < 0.05) suppression was found after 1 and 3 months when compared with the gel and the varnish forms. The gel (group B) tended to be slightly more effective than the varnish (group A). In the interdental plaque, the reduction of MS was less marked than in the saliva, and the three groups exhibited MS reductions of similar magnitude (20%) and duration, persisting up to 3 months. However, a high proportion (approximately 50%) of all interdental sites were relatively unaffected by the treatments. In conclusion, our results suggest that the interdental MS colonisation was difficult to combat, irrespective of CHX preparation and method, while the salivary levels were more easily affected. Daily tooth-brushing with a CHX-containing dentifrice was more effective in reducing MS in saliva compared with the gel or varnish applications.


Immune response to stage-specific surface antigens of the parasitic nematode Trichinella spiralis.
Rats were infected with the nematode Trichinella spiralis and the primary serum antibody response to antigenic surface proteins of infective larvae, intestinal worms, and newborn larvae was studies. 1 wk after infection, the sera contained antibodies to surface antigens of both infective larvae and intestinal worms. These early sera, however, failed to react with newborn larvae surface antigens. In addition, adsorption of sera with living intestinal worms or infective larvae removed antibodies to surface antigens of the homologous stage only. Finally, the time-course of appearance of antibodies that mediate eosinophil adherence to the surface of each stage of the parasite. We concluded that in a primary infection in rats, the surface proteins of T. spiralis used in this study are antigenically stage specific. Furthermore, they could be targets for the stage-specific, antibody-dependent eosinophil-mediated destruction of this parasite, known to occur in vitro.


Making maxillary barbels with a proximal-distal gradient of Wnt signals in matrix-bound mesenchymal cells.
The evolution of specific appendages is made possible by the ontogenetic deployment of general cell signaling pathways. Many fishes, amphibians and reptiles have unique skin appendages known as barbels, which are poorly understood at the cellular and molecular level. In this study, we examine the cell arrangements, cell division patterns, and gene expression profiles associated with the zebrafish maxillary barbel, or ZMB. The earliest cellular organization of the ZMB is an internal whorl of mesenchymal cells in the dermis of the maxilla; there is no epithelial placode, nor any axially-elongated epithelial cells as expected of an apical ectodermal ridge (AER). As the ZMB develops, cells in S-phase are at first distributed randomly throughout the appendage, gradually transitioning to a proliferative population concentrated at the distal end. By observing ZMB ontogenetic stages in a Wnt-responsive transgenic reporter line, TCFsiam, we identified a strongly fluorescent mesenchymal cell layer within these developing appendages. Using an in vitro explant culture technique on developing barbel tissues, we co-localized the fluorescent label in these cells with the mitotic marker EdU. Surprisingly, the labeled cells showed little proliferation, indicating a slow-cycling subpopulation. Transmission electron microscopy of the ZMB located these cells in a single, circumferential layer within the barbel's matrix core. Morphologically, these cells resemble fibroblasts or osteoblasts; in addition to their matrix-bound location, they are identified by their pancake-shaped nuclei, abundant rough endoplasmic reticulum, and cytoplasmic extensions into the surrounding extracellular matrix. Taken together, these features define a novel mesenchymal cell population in zebrafish, the "TCF(+) core cells." A working model of barbel development is proposed, in which these minimally mitotic mesodermal cells produce collagenous matrix in response to ectodermally-derived Wnt signals deployed in a proximal-distal gradient along the appendage. This documents a novel mechanism of vertebrate appendage outgrowth. Similar genetic signals and cell behaviors may be responsible for the independent and repeated evolution of barbel structures in other fish species.