Hysterosalpingography After Radiofrequency Endometrial Ablation and Hysteroscopic Sterilization as a Concomitant Procedure.
To evaluate the accuracy of hysterosalpingography (HSG) in patients who underwent concomitant radiofrequency endometrial ablation and hysteroscopic sterilization. This historical cohort study was conducted at a midwestern academic medical center. A total of 186 women (94 with combined procedure and 92 with sterilization alone) were identified as having undergone intervention between January 1, 2003, and June 30, 2011. Two reviewers blinded to the surgical procedure interpreted the standard clinically indicated HSGs in each group. The primary outcome assessed was the inability to rely on the microinserts for contraception based on HSG interpretation using manufacturers' guidelines (unsatisfactory HSG). Position of the devices and occlusion of tubes were assessed on all 3-month and, when available, all 6-month repeat HSGs. At the 3-month HSG, 5 of 76 (6.6%, 95% confidence interval [CI] 2.2-14.7%) in the sterilization-only group had unsatisfactory HSG compared with 13 of 71 (18.3%, 95% CI 10.1-29.3%) in the combined group (P=.03). After accounting for the seven patients who underwent repeat HSG at 6 months, 3 of 76 (3.95%, 95% CI 0.8-11.1%) in the sterilization-only group had unsatisfactory HSG compared with 13 of 71 (18.31%, 95% CI 10.1-29.3%) in the combined group (P=.005). After completing all clinically indicated HSGs, patients who undergo concomitant radiofrequency endometrial ablation and hysteroscopic sterilization have an approximate fivefold increase (odds ratio 5.45, 95% CI 1.48-20.0) in the rate of unsatisfactory HSG for purposes of documenting tubal occlusion. II.


Design Criteria for Architected Materials with Programmable Mechanical Properties Within Theoretical Limit Ranges.
Architected materials comprising periodic arrangements of cells have attracted considerable interest in various fields because of their unconventional properties and versatile functionality. Although some better properties may be exhibited when this homogeneous layout is broken, most such studies rely on a fixed material geometry, which limits the design space for material properties. Here, combining heterogeneous and homogeneous assembly of cells to generate tunable geometries, a hierarchically architected material (HAM) capable of significantly enhancing mechanical properties is proposed. Guided by the theoretical model and 745 752 simulation cases, generic design criteria are introduced, including dual screening for unique mechanical properties and careful assembly of specific spatial layouts, to identify the geometry of materials with extreme properties. Such criteria facilitate the potential for unprecedented properties such as Young's modulus at the theoretical limit and tunable positive and negative Poisson's ratios in an ultra-large range. Therefore, this study opens a new paradigm for materials with extreme mechanical properties.


The rising tide of fisheries instruments and the struggle to keep afloat.
Since agreement was reached in 1982 on the UN Convention on the Law of the Sea, and particularly since the conclusion of the 1992 UN Conference on Environment and Development, the rate of development of global instruments impacting on fisheries has escalated considerably and is apparently continuing to do so. A flood of global and regional instruments relevant to fisheries has been generated, including, for example, the 1973 Convention on International Trade in Endangered Species of Wild Fauna and Flora which pre-dates the UN Convention, the 1992 Convention on Biological Diversity, 1992 Agenda 21: Programme of Action for Sustainable Development, the 1993 FAO Agreement to Promote Compliance with International Conservation and Management Measures by Fishing Vessels on the High Seas, the 1995 UN Agreement for the Implementation of the Provisions of the United Nations Convention on the Law of the Sea of 10 December 1982 relating to the Conservation and Management of Straddling Fish Stocks and Highly Migratory Fish Stocks, the 1995 FAO Code of Conduct for Responsible Fisheries and its four international plans of action and strategy, and the 2001 FAO Reykjavik Declaration on Responsible Fisheries in the Marine Ecosystem reflecting the growing international interest in ecosystem approaches to fisheries. Most recent has been the 2002 World Summit on Sustainable Development's Plan of Implementation. These instruments have been motivated by real problems associated with environmental degradation and living resource depletion, in several cases specifically in connection with fisheries. They have attempted to address these problems, and each instrument is recognized as being a positive contribution towards the sustainable use of resources and ecosystems. However, taken collectively they form a large, often confusing and potentially overwhelming set of recommendations and requirements that is putting many fishery management agencies under severe pressure as they seek to implement them. This paper provides a brief overview of the range of recent instruments and their implications for sustainable fisheries management, considers the progress being made in implementing them, identifies general problems being encountered and how they might be ameliorated in the future. A key problem is a lack of political will, or political ability, to address effectively the problems facing fisheries and marine ecosystems. One consequence of this is that the agencies charged with fisheries management are not provided with adequate technical and financial capacity to implement the instruments in most, if not all, countries. The problem is especially acute in developing countries where they are strained by the full effects of "instrument implementation fatigue".


The bionic ear: principles and current status of cochlear prostheses.
The field of cochlear prostheses is reviewed, emphasizing the neurophysiological principles necessary for the development of a successful cochlear prosthesis. Pertinent auditory physiology is reviewed, and four conditions are proposed which, if met, should result in speech recognition by the patient with an implant. These conditions are: The surviving neural population must be adequate over the frequency distribution required to deliver the necessary information for speech discrimination. The central neural processing pattern for decoding and recognizing speech must have been established and still persist. The processing of the acoustic signal by the auditory system up to the level of the prosthesis interface must be understood and predictable from the acoustic stimulus. The relationship between the response patterns of the neural elements and the electrical stimulus must be well documented and controllable. The degree to which these conditions can presently be met is discussed, with some suggestions for future development. The function of the cochlear prosthesis is separated into a signal processing section and an electrical stimulus section. Two signal processing strategies are analog processing of the acoustic signal and speech feature extraction from the acoustic signal. Four possible electrical stimulation strategies are direct analog stimulation from the signal processor, pulse amplitude modulation, pulse width modulation, and stimulation designed to optimize the neural responses to electrical stimulation. Some of the present generation cochlear prostheses, including five approved by the FDA as investigational devices, are discussed according to this classification. The clinical results of testing these devices as aids to lip reading and as stand-alone speech reception aids are compared. All are a potential aid to lip reading. Some prosthesis designs have been implanted in patients who then showed exceptional open set speech discrimination. These exceptional patients have used both single channel and multichannel devices and devices with both analog processing and speech feature extraction strategies. These results are encouraging. More consistent and better speech reception is anticipated for the future as this field develops.


Point of care tobacco treatment sustains during COVID-19, a global pandemic.
Tobacco cessation treatment for cancer patients is essential to providing comprehensive oncologic care. We have implemented a point of care tobacco treatment care model enabled by electronic health record (EHR) modifications in a comprehensive cancer center. Data are needed on the sustainability of both reach of treatment and effectiveness over time, including the COVID-19 pandemic. Using EHR data from the pre-implementation (P: 5 months) and post-implementation periods (6 month-blocks, T1-T5 for a total of 30 months), we compared two primary outcomes: 1) reach of treatment among those smoking and 2) effectiveness assessed by smoking cessation among those smoking in the subsequent 6 month period. We analyzed the data using generalized estimation equation regression models. With the point of care tobacco treatment care model, reach of treatment increased from pre to post T5 (3.2 % vs. 48.4 %, RR 15.50, 95 % CI 10.56-22.74, p < 0.0001). Reach of treatment in all post periods (T1-T5 including the COVID-19 pandemic time) remained significantly higher than the pre period. Effectiveness, defined by smoking cessation among those smoking, increased from pre to post T2 before the pandemic (12.4 % vs. 21.4 %, RR 1.57, 95 % CI 1.31-1.87, p < 0.0001). However, effectiveness, while higher in later post periods (T3, T4), was no longer significantly increased compared with the pre period. A point of care EHR-enabled tobacco treatment care model demonstrates sustained reach up to 30 months following implementation, even during the COVID-19 pandemic and changes in healthcare prioritization. Effectiveness was sustained for 12 months, but did not sustain through the subsequent 12 months.


Allergic inflammation does not impact chemical-induced carcinogenesis in the lungs of mice.
Although the relationship between allergic inflammation and lung carcinogenesis is not clearly defined, several reports suggest an increased incidence of lung cancer in patients with asthma. We aimed at determining the functional impact of allergic inflammation on chemical carcinogenesis in the lungs of mice. Balb/c mice received single-dose urethane (1 g/kg at day 0) and two-stage ovalbumin during tumor initiation (sensitization: days -14 and 0; challenge: daily at days 6-12), tumor progression (sensitization: days 70 and 84; challenge: daily at days 90-96), or chronically (sensitization: days -14 and 0; challenge: daily at days 6-12 and thrice weekly thereafter). In addition, interleukin (IL)-5 deficient and wild-type C57BL/6 mice received ten weekly urethane injections. All mice were sacrificed after four months. Primary end-points were number, size, and histology of lung tumors. Secondary end-points were inflammatory cells and mediators in the airspace compartment. Ovalbumin provoked acute allergic inflammation and chronic remodeling of murine airways, evident by airspace eosinophilia, IL-5 up-regulation, and airspace enlargement. Urethane resulted in formation of atypical alveolar hyperplasias, adenomas, and adenocarcinomas in mouse lungs. Ovalbumin-induced allergic inflammation during tumor initiation, progression, or continuously did not impact the number, size, or histologic distribution of urethane-induced pulmonary neoplastic lesions. In addition, genetic deficiency in IL-5 had no effect on urethane-induced lung tumorigenesis. Allergic inflammation does not impact chemical-induced carcinogenesis of the airways. These findings suggest that not all types of airway inflammation influence lung carcinogenesis and cast doubt on the idea of a mechanistic link between asthma and lung cancer.


IL2-ricin fusion toxin is selectively cytotoxic in vitro to IL2 receptor-bearing tumor cells.
Fusion toxins consist of peptide ligands linked through amide bonds to polypeptide toxins. The ligand directs the molecule to the surface of target cells and the toxin enters the cytosol and induces cell death. Ricin toxin is an excellent candidate for use in fusion toxins because of its extreme potency, the extensive knowledge of its atomic structure, and the years of experience with RTA chemical conjugates in clinical trials. We synthesized a baculovirus transfer vector with the polyhedrin promoter followed sequentially from the 5' end with DNA encoding the gp67A leader sequence, the tripeptide ADP, IL2, another ADP tripeptide, and RTB. Recombinant baculovirus was generated in Sf9 insect cells and used to infect Sf9 cells. Recombinant IL2-RTB protein was recovered at high yields from day 5 insect cell supernatants, partially purified by affinity chromatography, and characterized. The recombinant product was soluble and immunoreactive with antibodies to RTB and IL2, bound asialofetuin and lactose, and reassociated with RTA. In the presence of lactose to block galactose-binding sites on RTB, the IL2-RTB-RTA heterodimer was selectively cytotoxic to IL2 receptor, bearing cells. Specific cytotoxicity could be blocked with IL2. Thus, we report a novel targeted plant toxin fusion protein with full biological activity.


Pregnancy-induced insulin resistance in the rat: assessment by glucose clamp technique.
To quantify and characterize the insulin resistance during pregnancy in the rat, a euglycemic hyperinsulinemic clamp was set up. Dose-response curves for the effects of five concentrations of insulin on glucose production, glucose utilization, and glucose clearance were performed in age-matched virgin and 19-day-pregnant rats. Glucose production and glucose utilization were measured by using [3-3H]-glucose. Glucose production was totally suppressed at plasma insulin concentrations higher than 1,000 microU/ml in the two groups. Insulin concentration causing half-maximal suppression of glucose production was about 70 microU/ml in virgin rats and 250 microU/ml in pregnant rats. Maximal glucose utilization was obtained at plasma insulin concentrations of 2,000 microU/ml. In pregnant rats maximal increment in glucose utilization was significantly lower (P less than 0.01) than in virgin rats. Insulin concentrations causing half-maximal stimulation of glucose utilization were 200 microU/ml in virgin rats and 500 in pregnant rats. As blood glucose concentration in virgin and pregnant rats was clamped at, respectively, 0.97 +/- 0.03 and 0.73 +/- 0.03 mg/ml, glucose clearance rates were calculated because this parameter is minimally affected by the changes in blood glucose concentrations. A normal maximal increment in glucose clearance in response to insulin was restored in pregnant rats but the rightward shift of the dose-response curve was maintained. Plasma insulin concentrations necessary for half-maximal increment of glucose clearance in the two groups were similar to that observed when the results were expressed as glucose utilization. Thus, insulin resistance during late pregnancy in the rat is characterized by a decreased sensitivity of liver and peripheral tissues to insulin.


Pharmaceuticals' removal by constructed wetlands: a critical evaluation and meta-analysis on performance, risk reduction, and role of physicochemical properties on removal mechanisms.
This paper presents a comprehensive and critical analysis of the removal of pharmaceuticals (PhCs), the governing physicochemical properties, and removal mechanisms in constructed wetlands (CWs). The average removal efficiency of the most widely studied 34 PhCs ranges from 21% to 93%, with the exception of one PhC that exhibited negative removal. Moreover, CWs are effective in significantly reducing the environmental risk caused by many PhCs. Based on risk assessment, 12 PhCs were classified under high risk category (oxytetracycline > ofloxacin > sulfamethoxazole > erythromycin > sulfadiazine > gemfibrozil > ibuprofen > acetaminophen > salicylic acid > sulfamethazine > naproxen > clarithromycin), which could be considered for regular monitoring, water quality standard formulation and control purposes. Biodegradation (aerobic and anaerobic) is responsible for the removal of the majority of PhCs, often in conjunction with other mechanisms (e.g., adsorption/sorption, plant uptake, and photodegradation). The physicochemical properties of molecules play a pivotal role in the elimination processes, and could serve as important predictors of removal. The correlation and multiple linear regression analysis suggest that organic carbon sorption coefficient (Log Koc), octanol-water distribution coefficient (Log Dow), and molecular weight form a good predictive linear regression model for the removal efficiency of PhCs (R2 = 0.65, P-value <0.05).


Evaluation of postural parathyroid hormone change in patients with primary hyperparathyroidism.
Purpose. In the present study, we aimed to investigate postural change of PTH in normal individuals and in patients with primary hyperparathyroidism (PHPT). Methods. Twenty-two patients with PHPT and nine healthy controls were enrolled. Following 12 h of fast, patients stayed in recumbent position for an hour and PTH and total Ca measurements were performed at the 45th and 60th minutes of resting. Afterwards, the patients resumed an upright posture for an hour and again blood samples were taken at the 45th and 60th minutes of standing. Results. In the PHPT group, mean PTH was calculated as 153.9 pg/mL in the recumbent position while it was 206.3 during upright position (Δ change was 47.7) (P < 0.001). In the control group mean serum PTH was measured as 41.2 pg/mL in the recumbent position while it was 44.8 pg/mL in the upright position (Δ change was 1.7) (P = 0.11). In both groups, serum Ca was higher in the upright position compared to the recumbent position (P < 0.001). Conclusion. Postural change of serum PTH is significant only in PHPT group. Postural PTH test may give a clue to the clinician when the diagnosis of PHPT is equivocal.


Validation of the IPSET score for thrombosis in patients with prefibrotic myelofibrosis.
Pre-fibrotic myelofibrosis (pre-PMF) and essential thrombocythemia (ET) are characterized by similarly increased rate of thrombotic events, but no study specifically analyzed risk factors for thrombosis in pre-PMF. In a multicenter cohort of 382 pre-PMF patients collected in this study, the rate of arterial and venous thrombosis after diagnosis was 1.0 and 0.95% patients/year. Factors significantly associated with arterial thrombosis were age, leukocytosis, generic cardiovascular risk factors, JAK2V617F and high molecular risk mutations, while only history of previous thrombosis, particularly prior venous thrombosis, was predictive of venous events. The risk of total thromboses was accurately predicted by the the international prognostic score for thrombosis in essential thrombocythemia (IPSET) score, originally developed for ET, and corresponded to 0.67, 2.05, and 2.95% patients/year in the low-, intermediate-, and high-risk categories. IPSET was superior to both the conventional 2-tiered score and the revised IPSET in this cohort of pre-PMF patients. We conclude that IPSET score can be conveniently used for thrombosis risk stratification in patients with pre-PMF and might represent the basis for individualized management aimed at reducing the increased risk of major cardiovascular events. Further refinement of the IPSET score in pre-PMF might be pursued by additional, prospective studies evaluating the inclusion of leukocytosis and/or adverse mutational profile as novel variables.


[HapMap project].
Haplotype map is the basis of SNP association studies in two aspects. One is to understand how SNPs are organized on chromosomes, thereby helping researchers to select tag SNPs to be examined. The other is to explore the presence of "hidden SNP" by haplotype analyses that is really associated with the disease. Although it is very difficult to forecast the future of SNP studies, the final and ideal methodology should be high--throughput whole genome sequencing with low price. At such stage, data mining technique will be very important since huge amount of genotype data should be handled and analyzed.


Analysis of genotype frequencies and interlocus association for the PM, DQA1, and D1S80 loci in four populations.
Allele frequencies of the LDLR, HBGG, GYPA, D7S8, GC, DQA1, and D1S80 loci are presented and genotypes are analyzed for each of four ethnic groups: African Americans (n = 200), US Caucasians (n = 200), US Hispanics (n = 200), and Japanese (n = 89). Hardy-Weinberg genotypic proportions were observed in all but two of the 28 population-locus tests undertaken. Those two instances are attributable to type I statistical error. Gametic equilibrium among loci is an assumption invoked for application of the product rule to utilize the discriminatory power from two or more loci simultaneously. Two statistical methods, a genotype matching statistic and log-linear modeling, were used to evaluate gametic disequilibrium. The match statistic, comparing observed to expected likelihood of genotypic identity for seven loci among pairs of individuals within the database, revealed only one statistically significant deviation among 20 tests. As expected, the probability of match was generally lowest in the test on all ethnic groups combined, indicating that allele frequencies differ among ethnic groups for some of the loci. This was confirmed with the statistic theta to measure ethnic stratification, in which about 0.10 of the genetic variation is apportioned among the four ethnic groups for four of the structural loci (LDLR, HBGG, GC, and DQA1), while for GYPA, D7S8, and D1S80, variation is more uniformly distributed among ethnic groups. Log-linear modeling was also applied to the five PM loci. The most parsimonious log-linear model included only three higher order terms: the two-way interactions of three of the PM loci with ethnic group. These three instances (LDLR, HBGG, and GC) indicated differences in allele frequencies between ethnic groups. No two or higher way interaction (disequilibrium) was observed among loci. In summary, the assumptions of Hardy-Weinberg and gametic equilibrium that facilitate the use of the five PM loci, DQA1 and D1S80 in forensic applications are consistent with the allele and genotype frequencies observed in these populations.


Development, Characterization, and In Vivo Evaluation of a Novel Aptamer (Anti-MUC1/Y) for Breast Cancer Therapy.
MUC1, the transmembrane glycoprotein Mucin 1, is usually found to be overexpressed in a variety of epithelial cancers playing an important role in disease progression. MUC1 isoforms such as MUC1/Y, which lacks the entire variable number of tandem repeat region, are involved in oncogenic processes by enhancing tumour initiation. MUC1/Y is therefore considered a promising target for the identification and treatment of epithelial cancers; but so far, the precise role of MUC1/Y remains to be elucidated. In this work, we developed and identified a DNA aptamer that specifically recognizes the splice variant MUC1/Y for the first time. The DNA aptamer could bind to a wide variety of human cancer cells, and treatment of MUC1/Y positive cells resulted in reduced growth in vitro. Moreover, MUC1/Y aptamer inhibited the tumour growth of breast cancer cells in vivo. The present study highlights the importance of targeting MUC1/Y for cancer treatment and unravels the suitability of a DNA aptamer to act as a new therapeutic tool.


Rigorous pH measurement in non-aqueous solution: measurement method and reference values in ethanol.
The recently introduced unified pH ([Formula: see text]) concept enables rigorous pH measurements in non-aqueous and mixed media while at the same time maintaining comparability to the conventional aqueous pH scale. However, its practical application is hindered by a shortage of reference [Formula: see text] values. In order to improve this situation, the European Metrology Research Project (EMPIR) UnipHied ("Realisation of a UnipHied pH scale") launched an interlaboratory comparison among highly experienced electrochemistry expert laboratories to assign the first such reference [Formula: see text] values by adopting an extensive statistical treatment of the reported measurement data: to phosphate buffer in water-ethanol mixture (50 wt% of ethanol) and ammonium formate buffer in pure ethanol. Two different measurement setups - one capable of being easily adopted in industrial applications - have been used to demonstrate the robustness of [Formula: see text] measurement. This is an important step towards wider adoption of the [Formula: see text] concept in practice, like liquid chromatography, biofuels analysis and electrocatalysis.


Peripheral opioid secretory pattern in anorexia nervosa.
The peripheral secretion of endogenous opioids was studied in 10 women with restrictive anorexia nervosa and 10 age- and sex-matched healthy controls. The circadian rhythm of beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH), and their responses to the administration of corticotropin releasing hormone (CRH, 1 micrograms/kg body weight, i.v.), clonidine (150 microgram, i.v.), domperidone (10 mg, i.v.), and 5-hydroxytryptophan (5-HTP, 200 mg, p.o.) were examined in patients and controls. The results revealed increased nocturnal secretion of beta-EP and diurnal-nocturnal secretion of beta-LPH with loss of circadian rhythmicity of both peptides, normal response to CRH stimulation, blunted response to clonidine and domperidine, and normal beta-EP and blunted beta-LPH response to 5-HTP stimulation. The data suggest a complex alteration of peripheral opioids and of central aminergic mechanisms that regulate proopiomelanocortin-derived peptide secretion and eating behavior.


Toward a unified model for predicting color quality of light sources.
Considering that the existing color quality (CQ) metrics for light sources cannot correlate well with the subjective evaluation, in an immersive environment equipped with a multichannel LED light source, a psychophysical experiment by categorical judgment method was carried out to assess the three perception-related CQ attributes of light sources in terms of naturalness, colorfulness, and preference. The experiment collected the subjective responses to these attributes of up to 41 metameric spectra at each of four test correlated color temperatures (CCTs) ranging from 2800 to 6500 K, which covers the usual white-light range for general lighting. The results indicate that preference exhibits relatively high correlation with naturalness and colorfulness, and naturalness is weakly related to colorfulness. Besides, 20 typical CQ metrics were adopted to examine their validity in characterizing the subjective data, confirming their limited performance. Meanwhile, the underlying relationship of these metrics and the subjective data was also analyzed by the multidimensional scaling, revealing that almost all metrics can correspond to one attribute of naturalness, colorfulness, and preference, and that the saturation level is identified as a critical factor affecting these attributes. Based on these results, a unified CQ model was developed with a multiple nonlinear regression equation combining the Illuminating Engineering Society of North America color rendition method. The model accords satisfactorily with the subjective evaluation, while being applicable to a wide range of CCTs.


Structure-activity relationship of a new series of reversible dual monoacylglycerol lipase/fatty acid amide hydrolase inhibitors.
The two endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), play independent and nonredundant roles in the body. This makes the development of both selective and dual inhibitors of their inactivation an important priority. In this work we report a new series of inhibitors of monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH). Among them, (±)-oxiran-2-ylmethyl 6-(1,1'-biphenyl-4-yl)hexanoate (8) and (2R)-(-)-oxiran-2-ylmethyl(4-benzylphenyl)acetate (30) stand out as potent inhibitors of human recombinant MAGL (IC(50) (8) = 4.1 μM; IC(50) (30) = 2.4 μM), rat brain monoacylglycerol hydrolysis (IC(50) (8) = 1.8 μM; IC(50) (30) = 0.68 μM), and rat brain FAAH (IC(50) (8) = 5.1 μM; IC(50) (30) = 0.29 μM). Importantly, and in contrast to the other previously described MAGL inhibitors, these compounds behave as reversible inhibitors either of competitive (8) or noncompetitive nature (30). Hence, they could be useful to explore the therapeutic potential of reversible MAGL inhibitors.


[1% carteolol hydrochloride eyedrops: long-term experience in the treatment of chronic open-angle glaucoma].
The response by 14 patients with open-angle glaucoma to treatment with carteolol 1% eye drops was investigated during a study lasting up to 15 months. Statistical analysis of the data revealed that carteolol had a highly significant IOP-lowering effect in all the patients studied. The mean decrease in IOP was as much as 41% of the initial value after the first day of treatment and after one week of treatment all the IOP values were close to 16-17 mm Hg. No long-term drift was noticed during the period of the study; no patient experienced any adverse reactions which could be related to the treatment with carteolol. This study therefore confirms the results of former investigations into the IOP-lowering effect of carteolol performed on Japanese subjects and classifies carteolol as a safe antiglaucoma agent which is also effective in Caucasian patients.


Lotus leaf extract and L-carnitine influence different processes during the adipocyte life cycle.
The cellular and molecular mechanisms of adipose tissue biology have been studied extensively over the last two decades. Adipose tissue growth involves both an increase in fat cell size and the formation of mature adipocytes from precursor cells. To investigate how natural substances influence these two processes, we examined the effects of lotus leaf extract (Nelumbo nucifera-extract solution obtained from Silab, France) and L-carnitine on human preadipocytes and adipocytes. For our in vitro studies, we used a lotus leaf extract solution alone or in combination with L-carnitine. Utilizing cultured human preadipocytes, we investigated lotus leaf extract solution-induced inhibition of triglyceride incorporation during adipogenesis and possible effects on cell viability. Studies on human adipocytes were performed aiming to elucidate the efficacy of lotus leaf extract solution to stimulate lipolytic activity. To further characterize lotus leaf extract solution-mediated effects, we determined the expression of the transcription factor adipocyte determination and differentiation factor 1 (ADD1/SREBP-1c) on the RNA- and protein level utilizing qRT-PCR and immunofluorescence analysis. Additionally, the effect of L-carnitine on beta-oxidation was analyzed using human preadipocytes and mature adipocytes. Finally, we investigated additive effects of a combination of lotus leaf extract solution and L-carnitine on triglyceride accumulation during preadipocyte/adipocyte differentiation. Our data showed that incubation of preadipocytes with lotus leaf extract solution significantly decreased triglyceride accumulation during adipogenesis without affecting cell viability. Compared to controls, adipocytes incubated with lotus leaf extract solution exhibited a significant increase in lipolysis-activity. Moreover, cell populations cultivated in the presence of lotus leaf extract solution showed a decrease in adipocyte differentiation capacity as indicated by a decrease in the ADD1/SREBP-1c signal. Importantly, our results demonstrated that a combination of lotus leaf extract solution and L-carnitine reduced triglyceride accumulation to a greater extent compared to incubation with either substance alone. Overall, our data demonstrate that a combination of lotus leaf extract and L-carnitine reduced triglyceride accumulation in human (pre)adipocytes by affecting different processes during the adipocyte life cycle. For this reason, this combination might represent a treatment option for obesity-related diseases.


Axin contains three separable domains that confer intramolecular, homodimeric, and heterodimeric interactions involved in distinct functions.
Axin is a major scaffold protein, interacting with diverse molecules involved in a number of signaling pathways. Axin can undergo dimer/oligomerization via its DIX domain. Here we show that whereas deletion of the DIX domain at the C terminus rendered Axin incapable of forming dimer, a larger deletion of the C-terminal region restored the ability of Axin to form dimers. Detailed analyses revealed that Axin actually contains two separate domains (D and I) in addition to the DIX domain for homodimerization. The D, I, and DIX domains alone can form homodimers. Interestingly, D and I domains strongly interact with each other, suggesting that Axin can form an intramolecular structure through D and I interaction in the absence of DIX. We also found that DIX-DIX homodimeric interaction is weak but that point mutations in the DIX domain abolished Axin homodimerization. We propose a model to suggest that Axin forms homodimeric interactions through three domains, D, I, and DIX. More importantly, lack of DIX-DIX interaction caused by point mutations in the DIX domain or deletion causes Axin to form an intramolecular loop through the D and I domains, disallowing homodimer formation. Ccd1 interacts with Axin D domain yet fails to interact with AxinDeltaDIX, confirming that D is masked after D-I looping. The Axin mutants that are defective in homodimer formation fail to activate JNK but have no effect on beta-catenin signaling. Our findings have thus provided a structural basis of conformational changes in Axin, which may underlie the diversity of Axin functions.


CInQ-03, a novel allosteric MEK inhibitor, suppresses cancer growth in vitro and in vivo.
The mitogen-activated protein kinase kinase 1 and 2 signaling pathway is a major component of the RAS (Rat sarcoma)/RAF (Radpidly accelerated fibrosarcoma)/MEK (mitogen-activated protein kinase kinase)/ERKs (Extracellular signal-regulated kinases) signaling axis that regulates tumorigenesis and cancer cell growth. MEK is frequently activated in various cancers that have mutations in the KRAS and BRAF oncogenes. Therefore, MEK has been suggested as a therapeutic target for inhibitor development against tumors that are dependent on the activating mutations in mitogen-activated protein kinase signaling. Herein, we report the discovery of three novel MEK inhibitors, herein referred to as CInQ-01, CInQ-03 and CInQ-06. All three inhibitors were highly effective in suppressing MEK1 and MEK2 in vitro kinase activity as well as anchorage-dependent and anchorage-independent cell growth. The inhibitory activity was associated with markedly reduced phosphorylation of ERKs and ribosomal S6 kinases. Furthermore, administration of CInQ-03 inhibited colon cancer cell growth in an in vivo xenograft mouse model and showed no skin toxicity. Overall, these results suggest that these novel MEK inhibitors might be used for chemotherapy or prevention.


[The guideline 'Detection of visual disorders at the age of 0-19' from the Dutch Association of Child Health Care].
The child health-care guideline 'Detection of visual disorders at the age of 0-19' draws attention to the importance of early detection of visual disorders and provides guidelines to child health-care workers for detecting disorders during routine check-ups. Children under the age of 3 are examined by the 'Early detection of visual disorders' method. Picture charts may be used for children from the age 3 onwards. From the age of 3.5 charts which follow the Snellen principle such as the Landolt-C chart should be used. Screening for refraction after the age of 7 and screening for colour blindness are not necessary. Children born before 32 weeks of pregnancy, children with a family history of visual disorders and mentally disabled children have an increased risk of visual disorders.


The Comparison of Robotic Single-Site Surgery to Single-Port Laparoendoscopic Surgery for the Treatment of Advanced-Stage Endometriosis.
Objective: To compare perioperative outcomes of robotic single-site (RSS) surgery with conventional single-port laparoendoscopic surgery for the treatment of advanced-stage endometriosis. Materials and Methods: This is a retrospective cohort study that included 120 patients who received single-port laparoendoscopic surgery or RSS surgery for the treatment of advanced-stage endometriosis at Ewha Womans University's Mokdong Hospital in Seoul, Korea between December 2014 and May 2017. Single-port laparoendoscopic cystectomy and adhesiolysis were performed in 52 patients (Single-port laparoendoscopic [SPL] group) and RSS cystectomy and adhesiolysis were performed in 68 patients (RSS group). Perioperative outcomes that we analyzed, included age, operative time, estimated blood loss, length of hospital stay, size of endometriosis, laterality of endometriosis, degree of endometriosis infiltration (i.e., deep versus not), and recurrence. Results: The patients in both groups were of similar ages. Longer operative times (107.8 ± 37.6 min for RSS group versus 76.9 ± 46.4 min for SPL group, P = .001) and more estimated blood loss (106.67 ± 171.67 mL for RSS group versus 57.1 ± 44.9 mL for SPL group, P = .001) were measured in the RSS group. However, the mean size of endometriosis was statistically larger (5.23 ± 2.53 cm for RSS group versus 4.37 ± 2.14 cm for SPL group, P = .030) and higher rates of more deeply infiltrative endometriosis (52 cases in RSS group, 76.5% versus 33 cases in SPL group, 63.5%) were observed in RSS group. Multicystic endometriosis occurred in 26 cases in the RSS group (38.2%). No significant differences were seen in terms of length of hospital stay (4.58 ± 0.61 of SPL group versus 4.59 ± 0.58 of RSS group, P = .862) or intraoperative and postoperative complications between the groups. Recurrence occurred in one case in the RSS group (1.9%). Conclusion: RSS surgery can be used in the treatment of advanced-stage endometriosis, especially in more complicated cases.


Involvement of the sigma1 receptor in the cocaine-induced conditioned place preference.
The sigma1 (sigma1) receptor constitutes a particular target of cocaine believed to be involved in some of its behavioral effects. In the present study, its involvement in the rewarding effect of cocaine was examined using the conditioned place preference (CPP) procedure. CPP was induced in C57Bl/6 mice injected repeatedly with cocaine (20 mg/kg, i.p.). The selective sigma1 receptor antagonists NE-100 and BD1047 (1-10 mg/kg, i.p.) significantly attenuated or blocked the cocaine-induced CPP. Animals treated centrally with a sigma1 receptor antisense oligodeoxynucleotide failed to develop cocaine-induced CPP, unlike mismatch controls. The sigma1 receptor thus appears to be critically involved in the development of the cocaine-induced CPP and, in consequence, may constitute a promising approach to blocking cocaine reward.


Clinical and genetic characterization of PYROXD1-related myopathy patients from Turkey.
Congenital myopathies (CMs) are a heterogeneous group of inherited muscle disorders characterized by muscle weakness at birth, while limb-girdle muscular dystrophies (LGMD) have a later onset and slower disease progression. Thus, detailed clinical phenotyping of genetically defined disease entities are required for the full understanding of genotype-phenotype correlations. A recently defined myopathic genetic disease entity is caused by bi-allelic variants in a gene coding for pyridine nucleotide-disulfide oxidoreductase domain 1 (PYROXD1) with unknown substrates. Here, we present three patients from two consanguineous Turkish families with mild LGMD, facial weakness, normal CK levels, and slow progress. Genomic analyses revealed a homozygous known pathogenic missense variant (c.464A>G, p.Asn155Ser) in family 1 with two affected females. In the affected male of family 2, we found this variant in a compound heterozygous state together with a novel frameshift variant (c.329_332delTCTG, p.Leu112Valfs*8), which is the second frameshift variant known so far in PYROXD1. We have been able to define a large homozygous region in family 1 sharing a common haplotype with family 2 in the critical region. Our data suggest that c.464A>G is a Turkish founder mutation. To gain deeper insights, we performed a systematic review of all published PYROXD1-related myopathy cases. Our analysis showed that the c.464A > G variant was found in 87% (20/23) of the patients and that it may cause either a childhood- or adult-onset phenotype, irrespective of its presence in a homozygous or compound heterozygous state. Interestingly, only four patients had elevated CK levels (up to 1000 U/L), and cardiac involvement was found in few compound heterozygous cases.


Blood Concentrations of Persistent Organic Pollutants and Unhealthy Metabolic Phenotypes in Normal-Weight, Overweight, and Obese Individuals.
Factors underlying metabolic phenotypes, such as the metabolically healthy but obese phenotype, remain unclear. Differences in metabolic phenotypes-particularly, among individuals with a similar body mass index-could be related to concentrations of persistent organic pollutants (POPs). To our knowledge, no studies have analyzed POPs and metabolic phenotypes in normal-weight persons. We investigated the relationships between serum concentrations of POPs and metabolic phenotypes in 860 normal-weight, overweight, and obese participants in the 2002 Catalan Health Interview Survey (Spain). POP concentrations were significantly higher in metabolically unhealthy than in metabolically healthy individuals. In models adjusting for body mass index and other confounders, hexachlorobenzene, β-hexachlorocyclohexane, and polychlorinated biphenyls were associated with the unhealthy metabolic phenotype and metabolic syndrome. Among normal-weight individuals, the adjusted prevalence ratio of having an unhealthy phenotype for the upper category of the sum of orders of the 6 mentioned POPs (all individually associated with metabolic phenotypes) was 4.1 (95% confidence interval: 1.7, 10.0). Among overweight and obese individuals, the corresponding prevalence ratio for the sum of polychlorinated biphenyls was 1.4 (95% confidence interval: 1.0, 1.8). Our results supported the hypothesis that POP concentrations are associated with unhealthy metabolic phenotypes, not only in obese and overweight individuals but also (and probably more strongly) in normal-weight individuals.


Zinc salts inactivate clinical isolates of herpes simplex virus in vitro.
Using a standard plaque assay and clinical isolates of herpes simplex virus (HSV), we have tested the ability of zinc salts to inactivate HSV. Virus was treated by incubation at 37 degrees C with zinc salts in morpholinepropanesulfonic acid-buffered culture medium and was then diluted and plated onto CV-1 cells for detection and quantitation of remaining infectious virus. Of 10 randomly chosen clinical isolates (five HSV type 1 [HSV-1] isolates and five HSV-2 isolates), seven were inactivated >98% by treatment in vitro with 50 mM zinc gluconate for 2 h and nine were inactivated >97% by treatment with zinc lactate. The effect was concentration dependent. With an HSV-1 isolate, 50 mM zinc gluconate or zinc lactate caused 100% inactivation, 15 mM caused 98 to 99% inactivation, and 5 mM caused 63 to 86% inactivation. With an HSV-2 isolate, 50 and 15 mM zinc gluconate caused 30% inactivation and 5 and 1 mM caused less than 9% inactivation, whereas 50 and 15 mM zinc lactate caused greater than 92% inactivation and 5 and 1 mM caused 37 and 26% inactivation, respectively. The ability of the zinc salts to inactivate HSV was not related to pH in the pH range of 6.1 to 7.6 since inactivation by zinc gluconate or zinc lactate in that pH range was 99.7 to 100% with a 2-h treatment with 50 mM zinc salt. Short (5-min) treatments of selected isolates with zinc gluconate, zinc lactate, zinc acetate, or zinc sulfate yielded inactivation rates of 0 to 55%.


Sports Participation in Children and Adolescents with Immune Thrombocytopenia (ITP).
We surveyed 278 pediatric hematologists/oncologists regarding how children with immune thrombocytopenia (ITP) are counseled for participation in sports. Results show substantial variation in physician perception of contact risk for different sports, and the advice offered about restriction of sport activities of affected children. Many physicians recommend restriction of sports when platelet counts are under 50 × 10(9) /L. Such restriction may affect the child's quality of life despite their having an overall benign disease.


EAHP statements survey 2016: sections 1, 3 and 4 of the European Statements of Hospital Pharmacy.
The 2016 European Association of Hospital Pharmacists (EAHP) Statements survey builds on previous surveys and focuses on sections 1, 3 and 4. To collect statistical data about the level of implementation of the Statements, and identify important barriers to their implementation. An online questionnaire was sent to all hospital pharmacies in EAHP member countries. Data were analysed by researchers from Keele University School of Pharmacy, UK and the EAHP Survey Group. If an incomplete survey was submitted, the quantitative data were not used, although any free-text responses were incorporated. The overall response rate was 16% (904 out of 5711 requests) with 730 complete responses. In the first part of the survey, data were collected on the hospital pharmacy setting. While almost half (n=335) of hospital pharmacies served over 500 beds, 77% (n=564) of hospital pharmacies had ≤10 pharmacists. In section B, evidence was gathered about the degree of implementation of sections 1, 3 and 4 of the Statements and the main barriers to, and drivers of, implementation. The questions related to production and compounding (section 3) received very positive responses (all questions from this section received at least a 70% positive response rate), indicating that responders are having less difficulty implementing these statements compared with others. The introductory statements and governance questions (section 1) received a more mixed response. Only 343 (47%) responses indicated that the pharmacists worked routinely as part of multidisciplinary team. Many of the questions relating to clinical pharmacy services (section 4) received a more negative response overall, with six questions receiving <50% positive responses. This iteration of the survey provides the EAHP with further insight into the implementation of the Statements across the member countries as well as the barriers to, and drivers of, implementation in sections 1, 3 and 4. This is essential to inform the plans for EAHP to best support their implementation.


Neural rhythmic symphony of human walking observation: Upside-down and Uncoordinated condition on cortical theta, alpha, beta and gamma oscillations.
Biological motion observation has been recognized to produce dynamic change in sensorimotor activation according to the observed kinematics. Physical plausibility of the spatial-kinematic relationship of human movement may play a major role in the top-down processing of human motion recognition. Here, we investigated the time course of scalp activation during observation of human gait in order to extract and use it on future integrated brain-computer interface using virtual reality (VR). We analyzed event related potentials (ERP), the event related spectral perturbation (ERSP) and the inter-trial coherence (ITC) from high-density EEG recording during video display onset (-200-600 ms) and the steady state visual evoked potentials (SSVEP) inside the video of human walking 3D-animation in three conditions: Normal; Upside-down (inverted images); and Uncoordinated (pseudo-randomly mixed images). We found that early visual evoked response P120 was decreased in Upside-down condition. The N170 and P300b amplitudes were decreased in Uncoordinated condition. In Upside-down and Uncoordinated conditions, we found decreased alpha power and theta phase-locking. As regards gamma oscillation, power was increased during the Upside-down animation and decreased during the Uncoordinated animation. An SSVEP-like response oscillating at about 10 Hz was also described showing that the oscillating pattern is enhanced 300 ms after the heel strike event only in the Normal but not in the Upside-down condition. Our results are consistent with most of previous point-light display studies, further supporting possible use of virtual reality for neurofeedback applications.


The amino-terminal fusion domain peptide of human immunodeficiency virus type 1 gp41 inserts into the sodium dodecyl sulfate micelle primarily as a helix with a conserved glycine at the micelle-water interface.
A peptide based on the N-terminal fusion domain of gp41 of human immunodeficiency virus type 1 (HIV-1) and its tryptophan analog were synthesized to examine the secondary structure in the micellar environment. Nuclear magnetic resonance (NMR), circular dichroism and electron paramagnetic resonance experiments indicated that the gp41 fusion peptide inserted into the micelle primarily as a helix (59%), with substantial beta-structure (26.7%). Deep penetration of the peptide into the apolar hydrocarbon core was supported by the results of fluorescence experiments in which the tryptophan analog exhibited a blue shift of about 30 nm in the presence of a sodium dodecyl sulfate micelle, in 1,2-dimyristoyl-rac-glycero-3-phosphocholine, and in 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine vesicular solutions. The results of spin label-attenuated 1H resonance experiments show that the region C-terminal to G16, which contains a turn structure, exhibited substantial interaction with the micelle, suggesting that it lies on the surface of micelle. Molecular simulation based on data from NMR experiments revealed a flexible hinge at residues 15 and 16 (alanine and glycine, respectively) from the N terminus of the peptide located at the micelle-solution interface. The highly conserved A15-G16 dipeptide may play a role in the function of fusion domain of HIV-1 envelope glycoprotein.


Interdigitated-electrode-based MEMS-scale piezoelectric energy harvester modeling and optimization using finite element method.
This paper presents a novel optimization method for interdigitated electrode (IDE)-based, cantilever-type piezoelectric energy harvesters at microelectromechanical system (MEMS) scale. A new two-stage approach based on the finite element method is proposed to examine the performance of such devices. First, detailed electrostatic poling simulations are presented. The results of these poling orientation simulations are used while calculating electrical energy and conversion efficiency in response to a constant external force. The proposed approach is used to find the optimum piezoelectric material thickness and IDE geometry for a cantilever beam which is constructed on top of a 4-μm Si structural layer and a 1-μm SiO2 isolation layer. Cantilever and IDE lengths are fixed at 320 μm and 240 μm, respectively, whereas the lead zirconate titanate (PZT) thickness, IDE finger widths, and number of finger pairs are varied. Maximum output energy of 0.37 pJ for a 15-μN force is obtained at a PZT thickness of 0.6 μm and an IDE consisting of 12 finger pairs. This energy is reduced to 1.5 fJ for 5 μm PZT thickness with 2 electrode finger pairs, which shows that device geometry has a significant impact on device performance. The proposed method presents an accurate framework for the rapid design and performance prediction of novel piezoelectric energy harvester structures.


Recombinant human epidermal growth factor (EGF) to enhance healing for diabetic foot ulcers.
This paper studies the healing effect of recombinant human epidermal growth factor (EGF) on chronic diabetic foot ulcers. A total of 89 patients (65 male and 24 female) aged from 36 to 82 years (average of 54) enrolled for the prospective, open-label trial, crossover study. Predetermined criteria were used for diagnosis and classification of ulcer. The average duration of ulcer was 6 months (range from 3 to 27 months) prior to study. Upon study, the ulcers were debrided and treated with hydrocolloid or composite dressing depending on the condition of the wound. If treatment effect was minimal using advanced dressing for 3 weeks, patients were crossed over to twice-a-day treatment with 0.005% EGF and advanced dressing. Among the patients, 21 patients showed improvement using hydrocolloid or composite dressing alone and 68 patients were crossed over to treatment with EGF and advanced dressing. In the EGF-treated patients, complete healing was noted in 52 patients within an average of 46 days (range from 2 to 14 weeks). Recurrence was not noted during the 6-month observation. But 5 patients showed new lesions different from the prior site. Sixteen patients required further interventions. This paper suggests that topical treatment with EGF combined with advanced dressing may have positive effects in promoting healing of chronic diabetic foot wounds.


[Volumetry of the testis using real-time sonography].
99 testes of corpses (death had occurred between 26 and 86 years) were examined via real time sonography in a water-bath, measuring their length, breadth and height. They were then exposed surgically and their volume (by litres) determined according to Archimedes' principle. The volume determined via testes sonography was set in relationship to the "real" volume according to Archimedes. A correction factor was found (corresponding to an ellipsoid) of f (sono) = 0.65 +/- 0.1 (for the rotation ellipsoid this is pi/6 = 0.524). On multiplication with the optimised factor f (sono) = 0.65 the best possible calculated testes volume was obtained. A direct comparison of both measurement methods showed a random mean error of 7% for the principle of Archimedes, whereas with sonographic determination of the volume a mean error of 15% must be taken into account. Whereas the accuracy of measurement increases with increasing volumes, both methods should be used with caution if the volumes are below 4 ml, since the possibilities of error are rather great.


IgG from patients with Lambert-Eaton syndrome blocks voltage-dependent calcium channels.
Lambert-Eaton syndrome, an autoimmune disorder frequently associated with small-cell carcinoma of the lung, is characterized by impaired evoked release of acetylcholine from the motor nerve terminal. Immunoglobulin G (IgG) antibodies from patients with the syndrome, applied to bovine adrenal chromaffin cells, reduced the voltage-dependent calcium channel currents by about 40 percent. When calcium was administered directly into the cytoplasm, however, the IgG-treated cells exhibited normal exocytotic secretion, as assayed by membrane capacitance measurement. Measurement with the fluorescent calcium indicator fura-2 indicated that the IgG treatment reduced potassium-stimulated increase in free intracellular calcium concentration. The pathogenic IgG modified neither kinetics of calcium channel activation nor elementary channel activity, suggesting that a reduction in the number of functional calcium channels underlies the IgG-induced effect. Therefore, Lambert-Eaton syndrome IgG reacts with voltage-dependent calcium channels and blocks their function, a phenomenon that can account for the presynaptic impairment characteristic of this disorder.


Association between an interleukin-13 promoter polymorphism and atopy.
Several studies indicate genetic involvement of Th2 cytokines in allergic diseases. Interleukin (IL)-13 has been mapped to the cytokine cluster on chromosome 5q31-33, which has been associated with atopic conditions. Recently, an association was reported between the T allele in a promoter polymorphism in the IL-13 gene (C to T exchange) at position -1055 and allergic asthma in a population study in the Netherlands. This observation was apparently confirmed in a case-control study using probands and spouses from a Dutch asthma family study, but the polymorphism in that study was reported to occur at position -1111. In the present study, we established that this polymorphism is located at position -1024 relative to the ATG translation initiation codon, and investigated whether it confers a genetic predisposition to atopic conditions and the Th1 condition multiple sclerosis (MS) in Caucasian subjects. We confirmed the association between the IL-13 -1024TT genoype and inhalation allergy (P = 2.4E-02). By combining the data from the three studies, we demonstrated a strong association (P = 1.09E-05) between the IL-13 -1024 marker and inhalation allergy. Furthermore, we showed for the first time that this association also exists in atopic dermatitis (P = 2.0E-02). No association with MS was found.


Microbial Perspectives: Mark Twain's Imaginative Experiment in Ethics.
While New Materialism and Object Oriented Ontology have provided frameworks to consider human relationships to nonhuman beings and objects in the twenty-first century, scientists and authors explored similar ethical dilemmas brought about by the newly identified presence of microorganisms in what had previously been imagined as a human world at the turn of the twentieth century. This essay considers Mark Twain's later fiction alongside the work of American bacteriologist Herbert W. Conn. Already invested in undermining human exceptionalism through scalar differences in his Mysterious Stranger manuscripts (1897-1908), Twain adapts Conn's bacteriology to experiment with microbial ethics in Three Thousand Years Among the Microbes (1905). While Conn uses microbes to assert scientific mastery and professional authority, Twain uses them to experiment with ethical structures on nonhuman scales. I argue that the failures of Twain's imaginative experiment dramatize the practical challenges to radically inclusive ethical structures proposed by New Materialists and others.


Surf4, cargo trafficking, lipid metabolism, and therapeutic implications.
Surfeit 4 is a polytopic transmembrane protein that primarily resides in the endoplasmic reticulum (ER) membrane. It is ubiquitously expressed and functions as a cargo receptor, mediating cargo transport from the ER to the Golgi apparatus via the canonical coat protein complex II (COPII)-coated vesicles or specific vesicles. It also participates in ER-Golgi protein trafficking through a tubular network. Meanwhile, it facilitates retrograde transportation of cargos from the Golgi apparatus to the ER through COPI-coated vesicles. Surf4 can selectively mediate export of diverse cargos, such as PCSK9 very low-density lipoprotein (VLDL), progranulin, α1-antitrypsin, STING, proinsulin, and erythropoietin. It has been implicated in facilitating VLDL secretion, promoting cell proliferation and migration, and increasing replication of positive-strand RNA viruses. Therefore, Surf4 plays a crucial role in various physiological and pathophysiological processes and emerges as a promising therapeutic target. However, the molecular mechanisms by which Surf4 selectively sorts diverse cargos for ER-Golgi protein trafficking remain elusive. Here, we summarize the most recent advances in Surf4, focusing on its role in lipid metabolism.


Benzo- and thienobenzo- diazepines: multi-target drugs for CNS disorders.
Benzodiazepines (BZ or BZD) are a class of gabaminergic psychoactive chemicals used in hypnotics, sedation, in the treatment of anxiety, and in other CNS disorders. These drugs include alprazolam (Xanax), diazepam (Valium), clonazepam (Klonopin), and others. There are two distinct types of pharmacological binding sites for benzodiazepines in the brain (BZ1 and BZ2), these sites are on GABA-A receptors, and are classified as short, intermediate, or long-acting. From the thienobenzodiazepine class (TBZ), Olanzapine (2-methyl-4-(4-methyl-l-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine) (Zyprexa) was used as an example to demonstrate the antagonism of this class of compounds for multiples receptors including: dopamine D1-D5, α-adrenoreceptor, histamine H1, muscarinic M1-M5 and 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3 and 5-HT6 receptors. Olanzapine is an atypical antipsychotic agent, structurally related to clozapine, and extensively used for the treatment of schizophrenia, bipolar disorder-associated mania, and the behavioral symptoms of Alzheimer's disease. The functional blockade of these multiple receptors contributes to the wide range of its pharmacologic and therapeutic activities, having relatively few side effects when compared to other antipsychotics agents. Thienobenzodiazepines (such as Olanzapine) are characterized as multi- receptor- targeted- acting- agents. This mini-review discusses these 2 drug classes that act on the central nervous system, the main active compounds used, and the various receptors with which they interact. In addition, we propose 12 olanzapine analogues, and generated Random Forest models, from a data set obtained from the ChEMBL database, to classify the structures as active or inactive against 5 dopamine receptors (D1, D2, D3, D4, D5 and D6), and dopamine transporter.


Participating in and delivering the ATEAM trial (Alexander technique lessons, exercise, and massage) interventions for chronic back pain: A qualitative study of professional perspectives.
To outline professionals' experiences of participation, perceived benefits and acceptability of the interventions delivered in the ATEAM trial (Alexander technique lessons, exercise, and massage), for patients with chronic or recurrent back pain. Qualitative study using in-depth interviews was conducted with a purposeful sample of twenty professionals (general practitioners (GPs), nurses, Alexander technique teachers, and massage therapists). Data were recorded, transcribed, and analysed thematically using the constant comparison method. Evidence of effectiveness GPs wanted an evidence base for the interventions, whilst nurses, Alexander technique teachers and massage therapists perceived patient reports of benefit as evidence. Professionals' perception of the acceptability of the intervention: professional perspectives differed, with GPs and nurses viewing the structured nature of exercise prescription and Alexander technique lessons as more beneficial and acceptable than massage in alleviating patients' back pain. Economic cost: the cost to patients pursuing Alexander technique lessons and massage was perceived to be a barrier outside the trial. Inter-professional communication: there was little communication between the professionals groups within the trial. Valuable insights have been gained into the perceived benefits and acceptability of exercise, Alexander technique lessons and massage as interventions for chronic back pain. Lessons in the Alexander technique with or without exercise, was perceived as more beneficial and acceptable than massage by professionals who participated and delivered the ATEAM trial interventions.


Phorbol ester-induced alkalinization of canine renal proximal tubular cells.
To determine whether exposure of renal proximal tubular cells to tumor-promoting phorbol esters results in intracellular alkalinization, we incubated suspensions of proximal tubular segments isolated from dog kidney with these compounds. Changes in intracellular pH were detected by measurements of the distribution of [14C]5,5-dimethoxazolidine-2-4-dione (DMO). Incubations of segments with 10(-6) M of the tumor-promoting phorbol esters phorbol-12,13-dibutyrate or 12-O-tetradecanoylphorbol-13-acetate (TPA), under conditions such that extracellular [Na+] greater than intracellular [Na+], effected intracellular alkalinization detectable within 1-2 min. Incubation with the inactive phorbol ester 4 alpha-phorbol did not. Incubation with as little as 10(-10) M phorbol-12,13-dibutyrate effected intracellular alkalinization. Incubation with 10(-12) M phorbol-12,13-dibutyrate did not. Alkalinization was not observed under conditions such that extracellular [Na+] = intracellular [Na+]. Alkalinization could be prevented by inclusion of 10(-3) M amiloride in incubations. Our findings are consistent with an action of tumor-promoting phorbol esters to stimulate Na+-H+ exchange across the plasma membrane of the renal proximal tubular cell. It is possible that the stimulation reflects a mechanism by which hormones and/or growth factors exert actions in proximal tubule.


Three-dimensional bioprinting of aneurysm-bearing tissue structure for endovascular deployment of embolization coils.
Various types of embolization devices have been developed for the treatment of cerebral aneurysms. However, it is challenging to properly evaluate device performance and train medical personnel for device deployment without the aid of functionally relevant models. Currentin vitroaneurysm models suffer from a lack of key functional and morphological features of brain vasculature that limit their applicability for these purposes. These features include the physiologically relevant mechanical properties and the dynamic cellular environment of blood vessels subjected to constant fluid flow. Herein, we developed three-dimensionally (3D) printed aneurysm-bearing vascularized tissue structures using gelatin-fibrin hydrogel of which the inner vessel walls were seeded with human cerebral microvascular endothelial cells (hCMECs). The hCMECs readily exhibited cellular attachment, spreading, and confluency all around the vessel walls, including the aneurysm walls. Additionally, thein vitroplatform was directly amenable to flow measurements via particle image velocimetry, enabling the direct assessment of the vascular flow dynamics for comparison to a 3D computational fluid dynamics model. Detachable coils were delivered into the printed aneurysm sac through the vessel using a microcatheter and static blood plasma clotting was monitored inside the aneurysm sac and around the coils. This biomimeticin vitroaneurysm model is a promising method for examining the biocompatibility and hemostatic efficiency of embolization devices and for providing hemodynamic information which would aid in predicting aneurysm rupture or healing response after treatment.


Whole genome sequencing in support of wellness and health maintenance.
Whole genome sequencing is poised to revolutionize personalized medicine, providing the capacity to classify individuals into risk categories for a wide range of diseases. Here we begin to explore how whole genome sequencing (WGS) might be incorporated alongside traditional clinical evaluation as a part of preventive medicine. The present study illustrates novel approaches for integrating genotypic and clinical information for assessment of generalized health risks and to assist individuals in the promotion of wellness and maintenance of good health. Whole genome sequences and longitudinal clinical profiles are described for eight middle-aged Caucasian participants (four men and four women) from the Center for Health Discovery and Well Being (CHDWB) at Emory University in Atlanta. We report multivariate genotypic risk assessments derived from common variants reported by genome-wide association studies (GWAS), as well as clinical measures in the domains of immune, metabolic, cardiovascular, musculoskeletal, respiratory, and mental health. Polygenic risk is assessed for each participant for over 100 diseases and reported relative to baseline population prevalence. Two approaches for combining clinical and genetic profiles for the purposes of health assessment are then presented. First we propose conditioning individual disease risk assessments on observed clinical status for type 2 diabetes, coronary artery disease, hypertriglyceridemia and hypertension, and obesity. An approximate 2:1 ratio of concordance between genetic prediction and observed sub-clinical disease is observed. Subsequently, we show how more holistic combination of genetic, clinical and family history data can be achieved by visualizing risk in eight sub-classes of disease. Having identified where their profiles are broadly concordant or discordant, an individual can focus on individual clinical results or genotypes as they develop personalized health action plans in consultation with a health partner or coach. The CHDWB will facilitate longitudinal evaluation of wellness-focused medical care based on comprehensive self-knowledge of medical risks.


Can allergic exposure provoke psychological symptoms? A double-blind test.
Clinical ecologists report that exposure to allergens can induce cognitive and emotional symptoms as well as somatic symptoms in susceptible individuals, but controlled tests are meager. In a test of the hypothesis that sublingual exposure to allergens would produce cognitive-emotional symptoms in allergy patients, double-blind provocative testing was conducted at an allergy clinic; 30 allergy patients complaining of at least one psychological symptom were selected. Self-report, heart-rate, and several mood and psychological performance measures were obtained. MMPI scores indicated a pathological sample. Reported cognitive-emotional symptoms were greater for allergens than for placebos (p = 0.001), while placebo symptoms were equal to base rate. Greater variability of heart rate change was found for allergens than for placebos (p = 0.008). Severe reactions occurred more frequently to allergens (p = 0.008). Severe reactions occurred more frequently to allergens (p = 0.02). Other dependent measures were not affected by the allergens or the placebos. It is concluded that allergens may contribute to psychopathology in some individuals.


Determining Health-Related Quality-of-Life Outcomes Using the SF-6D Preference-Based Measure in Patients Following Total Knee Arthroplasty.
The SF-6D, a health-related quality-of-life measure, assigns value to patients' perception of their health. We determined SF-6D values of 844 TKA patients, deduced clinical relevance of value changes using effect size, and compared these to clinical and functional improvements 6weeks, 3months, and 1 through 5years post-operatively. The SF-6D significantly improved at all follow-ups after 6weeks. The effect size indicated clinical relevance at every follow-up. The KSS improved at all follow-ups (+43, +51, +56, +57, +57 points), and LEAS scores improved at follow-ups after 6weeks (+1 point at 3months, +2 points thereafter), correlating with SF-6D changes. Deducing utility scores facilitates cost analyses, allowing clinicians to deduce quality-adjusted life-years and economic impacts of treatments.


Treatment of type 2 diabetes mellitus and risk of pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDAC) is the most common cancer of the exocrine part of the pancreas with poor prognosis. Up to 85% of PDAC patients are diagnosed with diabetes or hyperglycaemia at the time of diagnosis indicating that impaired glucose homeostasis is a common event in this cancer. A mechanism of association between PDAC and diabetes is very complex and still not fully understood. Currently, the various classes of anti-diabetic drugs are used in diabetes treatment. It is possible that specific types of anti-diabetic drugs for diabetes may have different impacts on pancreatic cancer development. Moreover, the intriguing question of whether diabetes can facilitate PDAC development remains unanswered. This paper presents the results of recent studies on the effect of the anti-diabetic treatment used on pancreatic cancer risk in diabetic patients.


Evidence for a psychotic posttraumatic stress disorder subtype based on the National Comorbidity Survey.
This study assessed the distribution of posttraumatic stress disorder (PTSD) symptoms and psychosis indicators among a large sample of individuals with a lifetime diagnosis of PTSD. The identification of a psychotic PTSD subtype was also predicted. Using data from the National Comorbidity Survey a latent class analysis was conducted on the PTSD symptoms of intrusion, avoidance, and hyperarousal and the psychosis hallucination and delusion indicators. Results indicated four latent classes, two of which had relatively high probabilities of endorsing the hallucination and delusion indicators. These classes were associated with a broad range of traumatic experiences. One particular class had high probabilities of endorsing both the psychosis indicators and the PTSD symptoms and was associated with a broad range of comorbid psychiatric disorders. There was a candidate class that met the characteristics expected to be evident in a psychotic PTSD subtype.


Adaptation of Candida albicans during gastrointestinal tract colonization.
Colonization of the gastrointestinal (GI) tract with Candida albicans (CA), the most common human fungal pathogen, is the first step towards the development of invasive infection. Yet the fungal virulence factors and host factors that modulate CA GI colonization are still poorly understood. In this review, we will review emerging evidence of the importance of select CA genetic determinants and CA's interaction with the host that contribute to its successful adaptation as a pathobiont in the human GI tract. Recent data reveal the importance of 1) CA genetic determinants; 2) host factors; and 3) environmental factors in modulating CA GI colonization in humans. As evidence continues to grow supporting the notion that the GI tract and its resident microbiota are an integral part of the host immune system, it will be critical for studies to interrogate the interaction of CA with the host (including both the host innate and adaptive immune system as well as the endogenous gut microbiota) in order to dissect the mechanisms of CA pathogenesis and thus lay the foundation for novel therapeutic approaches to prevent and/or treat invasive fungal infections.


Antinociceptive effect of Ferula assa-foetida oleo-gum-resin in mice.
Ferula assa-foetida L. is distributed throughout central Asia and Mediterranean area and grows wildly in Iran and Afghanistan. Asafoetida is an oleo-gum-resin that is the exudates of the roots of Ferula assa-foetida and some other Ferula species. In Iranian traditional medicine, asafoetida is considered to be sedative, analgesic, carminative, antispasmodic, diuretic, antihelmintic, emmenagogue and expectorant. The aim of this study was to evaluate the antinociceptive effect of asafoetida in mice. The analgesic activity of asafoetida (25, 50 and 100 mg/kg) was compared with that of sodium diclofenac (30 mg/kg) or morphine sulfate (8 mg/kg) by using hot plate and acetic acid induced writhing tests. In hot plate test, the percentage of maximum possible effect (%MPE) against the thermal stimulus at 15 min post treatment time point for all doses of asafoetida was significantly greater than the control group. The number of writhes in all three doses of asafoetida was significantly less than the control group. GraphPad Prism 5 software was used to analyze the behavioral responses. Data were analyzed using repeated measure one-way ANOVA and P<0.05 was considered as the significant level. According to our findings, asafoetida exhibited a significant antinociceptive effect on chronic and acute pain in mice. These effects probably involve central opioid pathways and peripheral anti-inflammatory action.


Critical damping conditions for third order muscle models: implications for force control.
Experimental results presented in the literature suggest that humans use a position control strategy to indirectly control force rather than direct force control. Modeling the muscle-tendon system as a third-order linear model, we provide an explanation of why an indirect force control strategy is preferred. We analyzed a third-order muscle system and verified that it is required for a faithful representation of muscle-tendon mechanics, especially when investigating critical damping conditions. We provided numerical examples using biomechanical properties of muscles and tendons reported in the literature. We demonstrated that at maximum isotonic contraction, for muscle and tendon stiffness within physiologically compatible ranges, a third-order muscle-tendon system can be under-damped. Over-damping occurs for values of the damping coefficient included within a finite interval defined by two separate critical limits (such interval is a semi-infinite region in second-order models). An increase in damping beyond the larger critical value would lead the system to mechanical instability. We proved the existence of a theoretical threshold for the ratio between tendon and muscle stiffness above which critical damping can never be achieved; thus resulting in an oscillatory free response of the system, independently of the value of the damping. Under such condition, combined with high muscle activation, oscillation of the system can be compensated only by active control.


HIV/AIDS surveillance in Egypt: current status and future challenges.
By international standards, HIV/AIDS prevalence is low in Egypt (< 0.1%). However, questions about the accuracy of this figure are coupled with fears of an imminent increase in prevalence, with evidence suggesting that, despite Egypt's conservative culture, high-risk behaviour is more widespread than commonly reported and the country's changing socioeconomic context is perpetuating this trend. Through an analysis of the current HIV/AIDS surveillance system in Egypt, this paper explores some of the unique challenges this country faces in dealing with the HIV/AIDS epidemic. It concludes that constraints, such as Egypt's cultural norms and laws, the population's lack of knowledge about HIV/AIDS and the bureaucratic health system, hinder the development and implementation of effective surveillance systems.


Biotransformation of homofolate from a growth inhibitor to a growth-promoting derivative.
Homofolic acid (HF) was found to inhibit the growth of Lactobacillus casei ATCC 7469 in 100 ng/ml or higher concentrations in the presence of folic acid (PGA) on short (24-48 h) incubation. HF blocked the uptake of 3HPGA into L. casei cell suspensions. On prolonged (3-5 days) incubation HF (greater than 10 ng/ml) promoted growth of L. casei both in the presence and absence of PGA. No growth was obtained when both PGA and HF were omitted. Thus, HF was apparently biotransformed from an inhibitory analog into a growth-promoting HF derivative. Indeed, sterile filtrates from HF-grown cultures supported growth of L. casei in a folate-free medium on short incubation, supporting the notion that a folate-like active compound was formed from HF on prolonged incubation with L. casei. In the presence of homopteorate (10-60 micrograms/ml) no transformation of HF into folate-active compounds took place.


The burden of cancer in Kentucky: the 1997 Kentucky cancer incidence report.
The purpose of collecting this important disease burden information is of course not simply for reports like this one. The real value lies in use of data for program planning, resource allocation, program design, and evaluation. Data in the annual KCR report and on the website should be a valuable resource for district and county health departments in their assessment of health problems in their area and as critical decisions are made about how to utilize limited intervention resources. The Kentucky Cancer Registry will continue to work very closely with the Community Outreach Division of the Kentucky Cancer Program to make this data available on an annual basis to District Cancer Councils to help guide their assessment and planning process. District and local health departments are encouraged to actively participate in the District Cancer Councils and in the cancer control activities guided by the regional community outreach coordinators.


Immune responses of breeding chickens to trivalent oil emulsion vaccines: responses to Newcastle disease and infectious bursal disease.
Bivalent Newcastle disease (ND)/infectious bursal disease (IBD) and trivalent ND/IBD/infectious bronchitis (IB) inactivated oil emulsion vaccines were prepared in the laboratory and evaluated under field conditions. Broiler breeder parent chickens previously vaccinated with live vaccines were inoculated with commercial monovalent ND and experimental bivalent or trivalent oil emulsion vaccines. The commercial vaccine induced a higher initial ND haemagglutination inhibition (HI) response than the experimental vaccines but, by 34 weeks after vaccination, the mean ND HI levels were not significantly different in any of the three flocks. All three vaccines provided sufficient ND immunity to protect against the clinical disease and egg production losses. The IBD responses of both flocks vaccinated with oil emulsion vaccine were similar to each other and only slightly lower than those flocks vaccinated with monovalent IBD oil emulsion vaccine in earlier experiments. Six weeks after vaccination, sufficient immunity was transferred to protect all the progeny against IBD challenge up to 33 days of age and some of them up to 45 days of age. Thirty-four weeks after vaccination of the parents with oil emulsion vaccine, the progeny were totally immune up to 27 days of age and some of them were immune until 37 days. Application of oil emulsion vaccines in bivalent or trivalent form did not impair the responses of the chickens to the monovalent components.


Hemodynamic changes during resuscitation after burns using the Parkland formula.
The Parkland formula (2-4 mL/kg/burned area of total body surface area %) with urine output and mean arterial pressure (MAP) as endpoints for the fluid resuscitation in burns is recommended all over the world. There has recently been a discussion on whether central circulatory endpoints should be used instead, and also whether volumes of fluid should be larger. Despite this, there are few central hemodynamic data available in the literature about the results when the formula is used correctly. Ten burned patients, admitted to our unit early, and with a burned area of >20% of total body surface area were investigated at 12, 24, and 36 hours after injury. Using transesophageal echocardiography, pulmonary artery catheterization, and transpulmonary thermodilution to monitor them, we evaluated the cardiovascular coupling when urinary output and MAP were used as endpoints. Oxygen transport variables, heart rate, MAP, and left ventricular fractional area, did not change significantly during fluid resuscitation. Left ventricular end-systolic and end-diastolic area and global end-diastolic volume index increased from subnormal values at 12 hours to normal ranges at 24 hours after the burn. Extravascular lung water: intrathoracal blood volume ratio was increased 12 hours after the burn. Preload variables, global systolic function, and oxygen transport recorded simultaneously by three separate methods showed no need to increase the total fluid volume within 36 hours of a major burn. Early (12 hours) signs of central circulatory hypovolemia, however, support more rapid infusion of fluid at the beginning of treatment.


Novel Bipolar High-Voltage Pulsed Radiofrequency Targeting the Cervical Sympathetic Chain for Treating Acute Herpetic Neuralgia.
Postherpetic neuralgia (PHN) in the oral, maxillofacial, neck, and upper limb regions is a refractory neuropathic pain and severely affects the quality of life of patients. Because of the absence of ideal treatments for this condition, relieving pain in the acute stage and preventing the occurrence of PHN are of great clinical significance. However, the optimal intervention for this acute herpetic neuralgia remains obscure. This study aimed to investigate whether bipolar high-voltage pulsed radiofrequency (PRF) targeting the cervical sympathetic chain could effectively treat acute herpetic neuralgia in the oral, maxillofacial, neck, and upper limb regions and reduce the incidence of PHN. A total of 60 patients with acute herpetic neuralgia in the oral, maxillofacial, neck, and upper limb regions were enrolled. The radiofrequency group (n = 30) received bipolar high-voltage PRF under ultrasound guidance at the level of the transverse processes of C6 and C7 to modulate the cervical sympathetic chain. In the sham group (n = 30), the electrodes were simply placed at the same position as in the radiofrequency group, but no radiofrequency energy was applied. The same treatment was repeated in each group after 72 hours. If patients were reported to have a visual analog scale (VAS) score ≥4, they would receive oral tramadol and gabapentin as rescue analgesics. The VAS score, Pittsburgh Sleep Quality Index (PSQI), 36-Item Short Form Health Survey (SF-36) score, use of tramadol and gabapentin, incidence of PHN, and adverse reactions were recorded to assess the effect and safety of therapy during three months of follow-up. Decreased VAS scores, PSQI scores, and improved SF-36 scores were detected in the two groups at different time points after treatment (all p < 0.05). The VAS scores, PSQI scores, use of tramadol and gabapentin, and incidence of PHN were significantly lower, whereas the SF-36 scores were significantly higher in the radiofrequency group than in the Sham group (all p < 0.05). No serious adverseness related to the treatment was detected in either group. Bipolar high-voltage PRF treatment targeting the cervical sympathetic chain could effectively relieve acute herpetic neuralgia in the oral, maxillofacial, neck, and upper limb regions and reduce PHN incidence. The efficacy and safety of this novel treatment make it worthy of recommendation for clinical application.


Symptom Prevalence and the Negative Emotional States in End-Stage Renal Disease Patients with or without Renal Replacement Therapy: A Cross-Sectional Analysis.
Limited comparative data are available on the symptom severity and burden of dialyzed versus nondialyzed end-stage renal disease (ESRD) patients and their association with negative emotional states. To investigate the prevalence of symptom burden and severity of ESRD patients and correlate the findings with their psychological status. This was a cross-sectional study of dialyzed (N = 87) and nondialyzed (N = 100) patients. The symptom burden and severity were determined using the Dialysis Symptom Index (DSI) and the psychological assessment using Depression Anxiety Stress Scale 21 (DASS-21). Symptom severity evaluated using the DSI was comparable in both groups with fatigue as the most common symptom (n = 141, 75.4%), followed by sleep-related, sexual dysfunction, and dry skin problems. The symptom burden for worrying, dry skin and mouth, decreased appetite, numbness, and leg swelling were significant in not dialyzed group (p < 0.05).The DASS-21 scores revealed that 11% of patients were depressed, 21.8% were stressed, and 15.6% were anxious (p < 0.030). The prevalence of psychological disturbances was associated with high symptom burden regardless of their treatment options (p < 0.005). Dialyzed patients showed a positive psychological status trend on DASS-21 assessment. The not dialyzed group consisted of 34% from comprehensive conservative group, 26% of choice-restricted conservative care, and 40% with no definitive future plan. There was no difference in the prevalence of symptom burden and severity, irrespective of the type of treatment. Psychological disturbances were associated with higher symptom burden and severity and, therefore, should be screened thoroughly to achieve optimal ESRD management.


[Papillomas in otorhinolaryngology: clinics, diagnostics and treatment].
The clinical, diagnostic, and therapeutic features of 257 papillomas of the ear, nose and throat were studied. These tumors were found in a population of about 500,000 inhabitants over a 20-year period (1973-1992). The clinical manifestations of papillomas were varied and more dependent on location than on the size or number of lesions. The most frequent symptom was a foreign body sensation. Twenty-four percent of cases were asymptomatic and the diagnosis was made during a general physical examination; such diagnoses were most frequent in the pharynx. The mean duration of symptoms before visiting a physician was 10 months (longer in papilloma of the oral cavity and shorter in the pharynx). The initial clinical diagnosis was correct in 63% of cases. Lesions of the oral cavity presented most diagnostic problems and those of the pharynx the least. A clinical diagnosis of cancer was made most often in the larynx. Treatment was surgical in every case. Twenty percent required more than one operation to remove the papilloma.


[Blood supply and oxygen consumption in the cat m. gastrocnemius during isometric tetanus in partial occlusion of the artery].
O2 consumption in resting m. gastrocnemius decreases in restriction of blood supply due to partial artery occlusion. This occurs in accordance with the degree of blood flow restriction. A dependence of postcontraction hyperemia on the degree of blood flow restriction was found. No hyperemia occurs in a severe restriction. In a less severe restriction the hyperemia occurs and a stronger one than in the control. The post-load increase of O2 consumption in partial artery occlusion occurs both in absence and in presence of the postcontraction hyperemia, but in the latter case the increase of O2 consumption is related to the degree of postcontraction increase of the blood flow.


Is There a Correlation Between Irritable Bowel Syndrome and Lactose Intolerance?
Irritable bowel syndrome (IBS) is a poorly understood gastrointestinal disorder that affects a significant percentage of the population and has a strong negative effect on the quality of life. The lack of known pathophysiologic mechanisms has made finding effective treatment strategies difficult. One of the common recommendations by clinicians is a trial of a lactose-free diet. We have wondered if there was sufficient evidence in the currently available literature to support such a recommendation. We have also looked into other possible relationships between malabsorption syndromes and IBS. All the articles used for this review have been found in the PubMed database. We have taken into consideration the possibility that there may be both genetic differences and differences in the gut microbiome between populations living in different geographic regions. Therefore, we have included articles from different geographic regions to increase the generalizability of the findings. While there is a plethora of evidence that IBS patients commonly report milk intolerance, we have not found any conclusive evidence to suggest an objective link between IBS and any known malabsorption syndromes, including lactose malabsorption. Furthermore, trials of lactase supplementation have not led to clinical benefit. We concluded that there was no evidence to support routinely recommending a lactose-free diet for patients diagnosed with IBS, but including hydrogen breath testing in routine workup of IBS is a reasonable clinical decision. Ultimately, we believe that more clinical trials and chemical studies of the feces are needed to determine the pathophysiology and explore possible dietary recommendations for patients with IBS.


Effects of Hydrogen/Deuterium Exchange on Protein Stability in Solution and in the Gas Phase.
Mass spectrometry (MS)-based techniques are widely used for probing protein structure and dynamics in solution. H/D exchange (HDX)-MS is one of the most common approaches in this context. HDX is often considered to be a "benign" labeling method, in that it does not perturb protein behavior in solution. However, several studies have reported that D2O pushes unfolding equilibria toward the native state. The origin, and even the existence of this protein stabilization remain controversial. Here we conducted thermal unfolding assays in solution to confirm that deuterated proteins in D2O are more stable, with 2-4 K higher melting temperatures than unlabeled proteins in H2O. Previous studies tentatively attributed this phenomenon to strengthened H-bonds after deuteration, an effect that may arise from the lower zero-point vibrational energy of the deuterated species. Specifically, it was proposed that strengthened water-water bonds (W···W) in D2O lower the solubility of nonpolar side chains. The current work takes a broader view by noting that protein stability in solution also depends on water-protein (W···P) and protein-protein (P···P) H-bonds. To help unravel these contributions, we performed collision-induced unfolding (CIU) experiments on gaseous proteins generated by native electrospray ionization. CIU profiles of deuterated and unlabeled proteins were indistinguishable, implying that P···P contacts are insensitive to deuteration. Thus, protein stabilization in D2O is attributable to solvent effects, rather than alterations of intraprotein H-bonds. Strengthening of W···W contacts represents one possible explanation, but the stabilizing effect of D2O can also originate from weakened W···P bonds. Future work will be required to elucidate which of these two scenarios is correct, or if both contribute to protein stabilization in D2O. In any case, the often-repeated adage that "D-bonds are more stable than H-bonds" does not apply to intramolecular contacts in native proteins.


Molecular characterization and evolution of carnivorous sundew (Drosera rotundifolia L.) class V β-1,3-glucanase.
A gene for β-1,3-glucanase was isolated from carnivorous sundew. It is active in leaves and roots, but not in digestive glands. Analyses in transgenic tobacco suggest its function in germination. Ancestral plant β-1,3-glucanases (EC 22.214.171.124) played a role in cell division and cell wall remodelling, but divergent evolution has extended their roles in plant defense against stresses to decomposition of prey in carnivorous plants. As available gene sequences from carnivorous plants are rare, we isolated a glucanase gene from roundleaf sundew (Drosera rotundifolia L.) by a genome walking approach. Computational predictions recognized typical gene features and protein motifs described for other plant β-1,3-glucanases. Phylogenetic reconstructions suggest strong support for evolutionary relatedness to class V β-1,3-glucanases, including homologs that are active in the traps of related carnivorous species. The gene is expressed in sundew vegetative tissues but not in flowers and digestive glands, and encodes for a functional enzyme when expressed in transgenic tobacco. Detailed analyses of the supposed promoter both in silico and in transgenic tobacco suggest that this glucanase plays a role in development. Specific spatiotemporal activity was observed during transgenic seed germination. Later during growth, the sundew promoter was active in marginal and sub-marginal areas of apical true leaf meristems of young tobacco plants. These results suggest that the isolated glucanase gene is regulated endogenously, possibly by auxin. This is the first report on a nuclear gene study from sundew.


Controlled synthesis of the DSF cell-cell signal is required for biofilm formation and virulence in Xanthomonas campestris.
Virulence of the black rot pathogen Xanthomonas campestris pv. campestris (Xcc) is regulated by cell-cell signalling involving the diffusible signal factor DSF. Synthesis and perception of DSF require products of genes within the rpf cluster (for regulation of pathogenicity factors). RpfF directs DSF synthesis whereas RpfC and RpfG are involved in DSF perception. Here we have examined the role of the rpf/DSF system in biofilm formation in minimal medium using confocal laser-scanning microscopy of GFP-labelled bacteria. Wild-type Xcc formed microcolonies that developed into a structured biofilm. In contrast, an rpfF mutant (DSF-minus) and an rpfC mutant (DSF overproducer) formed only unstructured arrangements of bacteria. A gumB mutant, defective in xanthan biosynthesis, was also unable to develop the typical wild-type biofilm. Mixed cultures of gumB and rpfF mutants formed a typical biofilm in vitro. In contrast, in mixed cultures the rpfC mutant prevented the formation of the structured biofilm by the wild-type and did not restore wild-type biofilm phenotypes to gumB or rpfF mutants. These effects on structured biofilm formation were correlated with growth and disease development by Xcc strains in Nicotiana benthamiana leaves. These findings suggest that DSF signalling is finely balanced during both biofilm formation and virulence.


Electrode comparison in pattern electroretinography.
In recent years, there has been great interest in recording the pattern electroretinogram (PERG) in glaucomatous and diabetic populations. The Dawson, Trick, and Litzkow thread electrode (DTLTE) and the gold foil electrode (GFE), commonly used for recording PERGs, were compared for variations in amplitude of response, test-retest variability, and patient comfort. Two study centers collected data on a total of 32 normal subjects. The subjects from the London center showed a slight (but not significant) preference for the DTLTE, and the Houston subjects also found the DTLTE to be significantly more comfortable (chi-square = 39, P less than 0.001). In both study groups, the GFE was found to produce a statistically larger amplitude of response than that obtained with the DTLTE. Significant differences were found regardless of the slow (transient, 3.1 Hz; F = 6.24; P = 0.0192) or fast (steady state, 8.3 Hz; F = 18.38; P = 0.0001) stimulus-presentation rate. Larger differences between the two electrodes occurred under steady-state conditions. Although there is no consensus as to the optimum recording conditions to obtain the subtle PERG, it appears the the GFE records larger responses than the DTLTE. However, test-retest data confirmed that the GFE records twice the amplitude of the DTLTE, and it also produced twice the variability (average percent difference over time for GFE, 15%; for DTLTE, 8%).