Impact of Partial and Comprehensive Smoke-Free Regulations on Indoor Air Quality in Bars.
In Korea, smoke-free regulations have been gradually implemented in bars based on venue size. Smoking bans were implemented in 2013 for bars ≥150 m², in 2014 for bars ≥100 m², and in 2015 for bars of all sizes. The purpose of this study was to determine indoor fine particle (PM2.5) concentrations in bars before and after implementation of the smoke-free policies based on venue size. Indoor PM2.5 concentrations were measured with real-time aerosol monitors at four time points: (1) pre-regulation (n = 75); (2) after implementing the ban in bars ≥150 m² (n = 75); (3) after implementing the ban in bars ≥100 m² (n = 107); and (4) when all bars were smoke-free (n = 79). Our results showed that the geometric mean of the indoor PM2.5 concentrations of all bars decreased from 98.4 μg/m³ pre-regulation to 79.5, 42.9, and 26.6 μg/m³ after the ban on smoking in bars ≥150 m², ≥100 m², and all bars, respectively. Indoor PM2.5 concentrations in bars of each size decreased only after the corresponding regulations were implemented. Although smoking was not observed in Seoul bars after smoking was banned in all bars, smoking was observed in 4 of 21 bars in Changwon. Our study concludes that the greatest decrease in PM2.5 concentrations in bars was observed after the regulation covering all bars was implemented. However, despite the comprehensive ban, smoking was observed in bars in Changwon. Strict compliance with the regulations is needed to improve indoor air quality further.


Methodology and grading for pulmonary hypertension evidence review and guideline development.
The American College of Chest Physicians assembled a multidisciplinary, geographically diverse panel of experts in the treatment of pulmonary hypertension to develop clinically relevant practice guidelines for the diagnosis and treatment of pulmonary hypertension in its many variations. That group of experts produced recommendations covering five topic areas, each related to a distinct set of patient-management decisions. This article describes the approach used to develop the guidelines, including identifying, evaluating, and synthesizing the evidence, assessing the strength of evidence pertinent to individual guidelines, and grading guideline recommendations.


Prophylactic therapy with granisetron in the prevention of vomiting after paediatric surgery. A randomized, double-blind comparison with droperidol and metoclopramide.
The antiemetic efficacy of droperidol, metoclopramide and granisetron was compared with placebo in the reduction of vomiting after paediatric surgery (the extremities; inguinal hernia; and phimosis) during general inhalational anaesthesia. One hundred children, ASA physical status I, 4-10 years of age, were enrolled in a prospectively, randomized, double-blind investigation and assigned to one of four treatment regimens: placebo (saline, n = 25), droperidol (50 micrograms.kg1, n = 25), metoclopramide (0.25 mg.kg-1, n = 25) or granisetron (40 micrograms.kg-1, n = 25). These drugs were administered intravenously (i.v.) after inhalation induction of anaesthesia. A complete response, defined as no emesis and no need for another rescue antiemetic during the first 24 h after anaesthesia, occurred in 60%, 76%, 68% and 88% of patients who had received placebo, droperidol, metoclopramide and granisetron, respectively (P < 0.05; overall Fisher's exact probability test). The incidence of adverse events postoperatively was not different among the treatment groups. In conclusion, granisetron 40 micrograms.kg-1 is a better antiemetic than droperidol and metoclopramide when compared to placebo for the prevention of postoperative emesis in children.


Subependymal and intraventricular hemorrhage in neonates. Early diagnosis by computed tomography.
Computed tomography was used to evaluate subependymal and intraventricular hemorrhage in 11 formalin-fixed brains obtained at autopsy from newborn infants from a population with a known high incidence of cerebral hemorrhage. After scanning, the brains were step-sectioned at levels corresponding to those of the scans. Subependymal and/or intraventricular hemorrhage was demonstrated in 6 of the 11 brains. There was a very close correlation between the scan images and the gross pathological findings in the affected brains. The authors conclude that computed tomography is an accurate method for the diagnosis of neonatal cerebral hemorrhage.


The catalytic efficiency of yeast ribonuclease III depends on substrate specific product release rate.
Members of the ribonuclease III (RNase III) family regulate gene expression by triggering the degradation of double stranded RNA (dsRNA). Hundreds of RNase III cleavage targets have been identified and their impact on RNA maturation and stability is now established. However, the mechanism defining substrates' reactivity remains unclear. In this study, we developed a real-time FRET assay for the detection of dsRNA degradation by yeast RNase III (Rnt1p) and characterized the kinetic bottlenecks controlling the reactivity of different substrates. Surprisingly, the results indicate that Rnt1p cleavage reaction is not only limited by the rate of catalysis but can also depend on base-pairing of product termini. Cleavage products terminating with paired nucleotides, like the degradation signals found in coding mRNA sequence, were less reactive and more prone to inhibition than products having unpaired nucleotides found in non-coding RNA substrates. Mutational analysis of U5 snRNA and Mig2 mRNA confirms the pairing of the cleavage site as a major determinant for the difference between cleavage rates of coding and non-coding RNA. Together the data indicate that the base-pairing of Rnt1p substrates encodes reactivity determinants that permit both constitutive processing of non-coding RNA while limiting the rate of mRNA degradation.


Occurrence of LINE, gypsy-like, and copia-like retrotransposons in the clonally propagated sweet potato (Ipomoea batatas L.).
Retrotransposons are a class of transposable elements that represent a major fraction of the repetitive DNA of most eukaryotes. Their abundance stems from their expansive replication strategies. We screened and isolated sequence fragments of long terminal repeat (LTR), gypsy-like reverse transcriptase (rt) and gypsy-like envelope (env) domains, and two partial sequences of non-LTR retrotransposons, long interspersed element (LINE), in the clonally propagated allohexaploid sweet potato (Ipomoea batatas (L.) Lam.) genome. Using dot-blot hybridization, these elements were found to be present in the ~1597 Mb haploid sweet potato genome with copy numbers ranging from ~50 to ~4100 as observed in the partial LTR (IbLtr-1) and LINE (IbLi-1) sequences, respectively. The continuous clonal propagation of sweet potato may have contributed to such a multitude of copies of some of these genomic elements. Interestingly, the isolated gypsy-like env and gypsy-like rt sequence fragments, IbGy-1 (~2100 copies) and IbGy-2 (~540 copies), respectively, were found to be homologous to the Bagy-2 cDNA sequences of barley (Hordeum vulgare L.). Although the isolated partial sequences were found to be homologous to other transcriptionally active elements, future studies are required to determine whether they represent elements that are transcriptionally active under normal and (or) stressful conditions.


[Dynamics of malaria transmission in Kafiné, a rice growing village in a humid savannah area of Côte d'Ivoire].
A study on malaria transmission based on samples of mosquitoes caught on human subjects was conducted from February to August 1995 in the rice growing area of Kafine, a village located in the Niakaramandougou district of northern Côte d'Ivoire. The village is surrounded by 117,500 acres of rice fields. Irrigation is sub-permanent in the rice field and harvests number two a year. During the 6 months of the study, 12.353 mosquitoes were caught. The average biting rate was 118.8 bites per man per night (b/m/n). Mansonia, Culex and Aedes represented only 17.5% of the total number of mosquitoes caught. Anopheles accounted for 82.5% of the number of anthropophilic mosquitoes. Anopheles gambiae s.s. represented 83.7% of the total Anopheles species. As a whole, the average biting rate recorded for the Anopheles was 98 b/m/n. The average biting rate of An. gambiae was 90.4 b/m/n. The highest rate (121.5 b/m/n) was recorded in April. During the dry and rainy season, the indoor biting cycle per hour of An. gambiae s.s. was studied from 6 p.m. to 6 a.m. In both seasons, a marked biting activity was noticed between 10 p.m. and 5 a.m. The average annual parity rate reached 40.2% but it ranged from 59.8% (n = 82) in February to 19% (n = 63) in May. The mean sporozoitic index of An. gambiae throughout the study period was 1.1% (14 positive salivary glands/1.251 dissected). The index ranged from 0 in April, May and June to 6.2 (n = 192) in July. The rate did not vary with rainfall but with the different stages of rice growing. The non-synchronisation of agricultural practises for each growing cycle seemed to be a conclusive factor in the transmission of malaria in this locality. Malaria transmission at Kafine can be characterised by 3 main elements: transmission is intensive with an estimated inoculation rate of 1 ib/m/n; transmission is more related to double phase rice cultivation (regardless of synchronisation on plots) than to rainfall; transmission shows particular variations linked to rice cultivation cycles with an increase during periods of ripeness and harvest. The nuisance caused by higher mosquito density has brought people to comply with use of pyrethroid impregnated bed nets advocated for wide use by the National Malaria Control Program.


The imperative for regenerative agriculture.
A review is made of the current state of agriculture, emphasising issues of soil erosion and dependence on fossil fuels, in regard to achieving food security for a relentlessly enlarging global population. Soil has been described as "the fragile, living skin of the Earth", and yet both its aliveness and fragility have all too often been ignored in the expansion of agriculture across the face of the globe. Since it is a pivotal component in a global nexus of soil-water-air-energy, how we treat the soil can impact massively on climate change - with either beneficial or detrimental consequences, depending on whether the soil is preserved or degraded. Regenerative agriculture has at its core the intention to improve the health of soil or to restore highly degraded soil, which symbiotically enhances the quality of water, vegetation and land-productivity. By using methods of regenerative agriculture, it is possible not only to increase the amount of soil organic carbon (SOC) in existing soils, but to build new soil. This has the effect of drawing down carbon from the atmosphere, while simultaneously improving soil structure and soil health, soil fertility and crop yields, water retention and aquifer recharge - thus ameliorating both flooding and drought, and also the erosion of further soil, since runoff is reduced. Since food production on a more local scale is found to preserve the soil and its quality, urban food production should be seen as a significant potential contributor to regenerative agriculture in the future, so long as the methods employed are themselves 'regenerative'. If localisation is to become a dominant strategy for dealing with a vastly reduced use of fossil fuels, and preserving soil quality - with increased food production in towns and cities - it will be necessary to incorporate integrated ('systems') design approaches such as permaculture and the circular economy (which minimise and repurpose 'waste') within the existing urban infrastructure. In addition to growing food in urban space, such actions as draught-proofing and thermally insulating existing building stock, and living/ working on a more local scale, would serve well to cut our overall energy consumption. In order to curb our use of fossil fuels, methods for reducing overall energy use must be considered at least equally important to expanding low-carbon energy production. In synopsis, it is clear that only by moving from the current linear, 'take, make, dispose (waste-creation)' model for resource-consumption, to the systemic, circular alternative of 'reduce, reuse, recycle, regenerate', are we likely to meet demands for future generations.


Effect of Heat Treatment Condition on the Flow Behavior and Recrystallization Mechanisms of Aluminum Alloy 7055.
The flow behavior and the microstructural evolution of aluminum alloy 7055 in two heat treatment conditions (homogenized vs. pre-rolled, solution treated, stretched and naturally aged (T3)) were investigated for a height reduction of 60% with deformation temperatures ranging from 370 °C to 450 °C and strain rates ranging from 0.01 s-1 to 10 s-1. Flow stress decline ratio maps as a function of deformation temperature and strain rate were produced along with processing maps at a strain of 0.8 to reveal optimum hot-working conditions for deformation at strain rates of 0.01 s-1 to 0.1 s-1. The results showed that the stress drop ratio during deformation is higher for the homogenized condition than for the pre-rolled, T3 condition. A higher degree of recrystallization after deformation was observed in the pre-rolled, T3 condition due to finer second phase particles, smaller grain size, and more numerous sub-grains. The mechanism for deformation softening is discussed in the context of grain boundary characteristics.


Total hip arthroplasty with bone graft for acetabular protrusion in rheumatoid arthritis.
Abstract Twenty-five hips in 19 rheumatoid arthritis (RA) patients with protrusio acetabuli were followed up, both clinically and radiographically, for more than 9 years after total hip arthroplasty (THA), that was performed with a bone graft to reinforce the medial acetabular wall. Radiographs were taken preoperatively and every 6 months postoperatively. Clinical assessments of pain, gait, and range of motion of the hips were obtained preoperatively and every year postoperatively using the Japanese Orthopaedic Association hip-scoring system. Radiographs showed that bony union had occurred in all cases. Six acetabular components were loose, but no femoral components became loose during the 9-year period. The clinical evaluation showed that relief of pain was very significant. The range of motion of the hip joints also improved from 12 points to 16.6 points after 9 years. Walking ability improved, but is becoming worse as time goes by. The radiographic results were compared with the results of a THA group with RA that had not had a bone graft. The rate of loosening of the THA without a bone graft was significantly higher than that of THA with a bone graft. We concluded that bone grafting for protrusio acetabuli was a very useful procedure.


Mechanics of the human femoral adventitia including the high-pressure response.
Adventitial mechanics were studied on the basis of adventitial tube tests and associated stress analyses utilizing a thin-walled model. Inflation tests of 11 nonstenotic human femoral arteries (79.3 +/- 8.2 yr, means +/- SD) were performed during autopsy. Adventitial tubes were separated anatomically and underwent cyclic, quasistatic extension-inflation tests using physiological pressures and high pressures up to 100 kPa. Associated circumferential and axial stretches were typically <20%, indicating "adventitiosclerosis." Adventitias behaved nearly elastically for both loading domains, demonstrating high tensile strengths (>1 MPa). The anisotropic and strongly nonlinear mechanical responses were represented appropriately by two-dimensional Fung-type stored-energy functions. At physiological pressure (13.3 kPa), adventitias carry ~25% of the pressure load in situ, whereas their circumferential and axial stresses were similar to the total wall stresses (~50 kPa in both directions), supporting a "uniform stress hypothesis." At higher pressures, they became the mechanically predominant layer, carrying >50% of the pressure load. These significant load-carrying capabilities depended strongly on circumferential and axial in-vessel prestretches (mean values: 0.95 and 1.08). On the basis of these results, the mechanical role of the adventitia at physiological and hypertensive states and during balloon angioplasty was characterized.


A genetic algorithm based approach to fiber design for high coherence and large bandwidth supercontinuum generation.
We present a new approach to the design of optical microstructured fibers that have group velocity dispersion (GVD) and effective nonlinear coefficient (gamma ) tailored for supercontinuum (SC) generation. This hybrid approach combines a genetic algorithm (GA) with pulse propagation modeling, but without include it into the GA loop, to allow the efficient design of fibers that are capable of generating highly coherent and large bandwidth SC in the mid-infrared (Mid-IR) spectrum. To the best of our knowledge, this is the first use of a GA to design fiber for SC generation. We investigate the robustness of these fiber designs to variation in the fiber's structural parameters. The optimized fiber structure based on a type of tellurite glass (70TeO(2) - 10 Na(2)O - 20 ZnF(2)) is predicted to have near-zero group velocity dispersion (< +/-2 ps/nm/km) from 2 to 3 microm, and a effective nonlinear coefficient of gamma approximately 174 W(-1)km(-1) at 2 microm. The SC output of this fiber shows a significant bandwidth and coherence increase compare to a fiber with a single zero group velocity dispersion wavelength at 2 microm.


Improved Functional Outcomes Following Operative Treatment of Midshaft Clavicle Fractures in an Active Duty Population.
Clavicle fractures are common orthopedic injuries that occur in a young active population and are even more common in the military. Military fitness test data presents the unique opportunity to analyze functional ability with regard to military-specific activities. The primary goal of this study was to compare functional outcomes using military fitness test data between operative and non-operative treatment of midshaft clavicle fractures. We performed a retrospective review of active-duty U.S. Navy and Marine patients with midshaft clavicle fractures treated at our institution over a seven-year period. There were 94 and 153 patients in our operative and non-operative cohorts, respectively. Average follow-up time from the date of injury or surgery was 28 months. The rate of infection in the operative group (4%) was significantly greater than in the non-operative group (0%, p = 0.023). The rate of non-union in the operative group (3%) was significantly lower than in the non-operative group (14.5%, p = 0.004). The rate of symptomatic malunion in the operative group (0%) was significantly different from that in the non-operative group (4.6%, p = 0.036). There was no significant difference in the rate of revision surgery between the operative (9.2%) and non-operative (13.2%) groups (p = 0.105). A total of 51 marines met inclusion criteria for our functional outcome analysis using Marine Corps Physical Fitness Test (PFT) data. Of those who underwent operative fixation, 68% were able to meet or surpass their pre-injury average amount of pull-ups in their first PFT after surgery and 88% by the next PFT at least one year after surgery. While 69% of non-operative patients met their pre-injury average in their first PFT, only 57% maintained this level at least one year after surgery. This difference was statistically significant. In our functional outcome subgroup analysis, we found improved outcomes for pull-ups at least one year out when midshaft clavicle fractures are treated operatively compared to non-operatively. While similar findings in the literature are based on functional outcome questionnaires, physical fitness performance data has not been reported on to our knowledge.


Mucin overproduction in chronic inflammatory lung disease.
Mucus overproduction and hypersecretion are commonly observed in chronic inflammatory lung disease. Mucins are gel-forming glycoproteins that can be stimulated by a variety of mediators. The present review addresses the mechanisms involved in the upregulation of secreted mucins. Mucin induction by neutrophil elastase, bacteria, cytokines, growth factors, smoke and cystic fibrosis transmembrane conductance regulator malfunction are also discussed.


Rhabdomyolysis in McArdle disease caused by scuba diving.
McArdle disease is a glycogen storage disease that results in rhabdomyolysis during intense exercise. A number of different triggers have been described. We evaluated a patient with McArdle disease who presented with rhabdomyolysis after recreational scuba diving. There was no concern for barotrauma or decompression sickness. His symptoms resolved with standard-of-care management for non-diving-related rhabdomyolysis. Features of his experience provoked questions about the diving-related factors contributing to his presentation. We present the case and explore possible mechanisms of diving-related injury in patients with McArdle disease, including the possible effects of hyperoxia, hyperbaria, hypothermia and strenuous activity.


Emotional scene remembering: A combination of disturbing and facilitating effects of emotion?
An emotion-induced memory trade-off effect is frequently reported when participants have to memorize complex items that include both neutral and emotional features. This bias corresponds to better remembering of central emotional information accompanied by poor performance related to neutral background information. Although the trade-off effect has been mainly associated with attentional bias toward emotional content, findings suggest that other non-attentional cognitive processes could also be involved. The aim of this work was to assess whether emotional effects would be reported apart from their influence on attentional processing in an immediate delay memory task. Three studies were conducted. In Study 1, manipulation of the diffusion quality of emotional content allowed us to select focal emotional pictures vs. diffuse emotional pictures, which prevented attentional focus. The two studies that followed consisted of a recognition task of low- and high-complexity pictures in which we used partial visual cues during the test that could display either the emotional elements (i.e., central patch cues, Study 2) or the peripheral elements (i.e., peripheral patch cues, Study 3) of the focal emotional pictures. Results from Studies 2 and 3 replicated traditional trade-off effects only for high-complexity pictures. In addition, diffuse emotional pictures were associated with lower memory performance than were neutral pictures, suggesting that emotion features could both disturb and enhance (via their attentional effect) encoding processes.


Ningiella ruwaisensis gen. nov., sp. nov., a member of the family Alteromonadaceae isolated from marine water of the Arabian Gulf.
Strain B66T was isolated from a marine water sample collected at Al Ruwais, located on the northern tip of Qatar. Cells were Gram-stain-negative, strictly aerobic and short- rod-shaped with a polar flagellum. The isolate was able to grow at 15-45 °C (optimum, 30 °C), at pH 5-11 (optimum, pH 6.5-8) and with 0-6 % NaCl. 16S rRNA gene sequence analysis revealed that strain B66T was affiliated with the family Alteromonadaceae, sharing the highest sequence similarities to the genera Alteromonas (93.7-95.4 %), Aestuariibacter (94.0-95.1 %), Agaribacter (93.3-93.7 %), Glaciecola (92.0-93.7 %), Marisendiminitalea (93.2-93.3 %) and Planctobacterium (92.9 %). In the phylogenetic trees, strain B66T demonstrated the novel organism formed a distinct lineage closely associated with Aestuariibacter and Planctobacterium. Major fatty acids were C16 : 0, summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c/iso-C15 : 0 2-OH and iso-C15 : 0 3-OH. The major respiratory quinone was ubiquinone-8 and the major polar lipids are phosphatidylglycerol and phosphatidylethanolamine. The DNA G+C content derived from the genome was 43.2 mol%. Based on the phenotypic, chemotaxonomic, phylogenetic and genomic data, strain B66T is considered to represent a novel species and genus for which the name Ningiella ruwaisensis gen. nov., sp. nov., is proposed. The type strain is B66T (=QCC B003/17T=LMG 30288 T=CCUG 70703T).


A low-coverage 3' RNA-seq to detect homeolog expression in polyploid wheat.
Although allopolyploid species are common among natural and crop species, it is not easy to distinguish duplicated genes, known as homeologs, during their genomic analysis. Yet, cost-efficient RNA sequencing (RNA-seq) is to be developed for large-scale transcriptomic studies such as time-series analysis and genome-wide association studies in allopolyploids. In this study, we employed a 3' RNA-seq utilizing 3' untranslated regions (UTRs) containing frequent mutations among homeologous genes, compared to coding sequence. Among the 3' RNA-seq protocols, we examined a low-cost method Lasy-Seq using an allohexaploid bread wheat, Triticum aestivum. HISAT2 showed the best performance for 3' RNA-seq with the least mapping errors and quick computational time. The number of detected homeologs was further improved by extending 1 kb of the 3' UTR annotation. Differentially expressed genes in response to mild cold treatment detected by the 3' RNA-seq were verified with high-coverage conventional RNA-seq, although the latter detected more differentially expressed genes. Finally, downsampling showed that even a 2 million sequencing depth can still detect more than half of expressed homeologs identifiable by the conventional 32 million reads. These data demonstrate that this low-cost 3' RNA-seq facilitates large-scale transcriptomic studies of allohexaploid wheat and indicate the potential application to other allopolyploid species.


Communicating and advocating for science and medicine: beyond the basics.
I have discussed several advocacy strategies to improve effective communications for those motivated to do the necessary work to make a difference in policy decisions involving science and health care. I encourage you to get involved personally with members of Congress, their key "staffers," and to contribute financially to their election efforts. Other suggestions are self-evident, for example, think strategically, only advocate for important policies and do not "over promise" or "under deliver." If you "get to yes," stop negotiating and leave gratefully. Remember, you are operating in a high stakes arena and while you understand the intended consequences, you may misjudge unintended consequences that could diminish success. But if you want to make a difference, you must become a "player in the policy and political game." And if you "get in the game," you should play to win!


ATM gene mutations in former uranium miners of SDAG Wismut: a pilot study.
Ataxia-telangiectasia is an autosomal recessive disease characterized by neurological and immunological symptoms, radiosensitivity and cancer predisposition. Heterozygous carriers of an ataxia-telangiectasia gene mutation are predisposed to epithelial cancers. We initiated a study to elucidate the frequency and clinical relevance of ATM gene mutations in former uranium miners exposed to high levels of radiation from radon and its decay products. Former uranium miners with Schneeberg lung cancer (n=48), former uranium miners suffering from silicosis (n=60) and uranium miners without occupational lung disorders (n=102) were investigated for nine mutations in the ATM gene. One gastric and one prostate cancer occurred in the group of miners without occupational lung diseases. Mutation analyses for S707P, IVS10-6Tright curved arrow G, 2250Gright curved arrow A, E1978X, R2443X, 3801delG, S49C and D2625E-A2626P were performed using genomic DNA obtained from peripheral blood samples. Three ATM gene alterations (S707P, S49C or IVS10-6Tright curved arrow G) were observed. Of all cancer patients, 8.0% were heterozygous, but only 1.9% of the non-cancer controls were [OR=4.6; 95% confidence interval (CI), 0.8-26.8]. In this pilot study a major role of six ATM gene mutations could not be revealed for cancer predisposition in former uranium miners. The results leave the possibility of a moderate risk associated with more subtle ATM gene alterations.


Is There a Rationale for Structural Quality Assurance in Esophageal Surgery?
Advances regarding perioperative mortality rates and oncological outcomes after esophagectomy have been reported extensively by specialized high-volume centers in Europe and the USA over the last decade. However, recent database analyses reveal that the perioperative mortality of esophagectomy remains high in these countries, indicating a discrepancy between surgical quality in baseline hospitals and specialized centers. This article provides an overview over the existing literature on the correlation between structural quality, procedural volume, and surgical outcome in e- sophageal surgery. Structural, procedural and outcome measures can be used to assess the quality of surgical treatment and perioperative management. Surgical procedures on the esophagus for both benign and malignant diseases are rare and typically associated with high perioperative morbidity and mortality. Usually, direct outcome measures do not provide enough statistical power to actually identify differences in surgical quality between hospitals, making structural quality measures the only feasible parameter to compare the quality of e- sophageal surgery among different centers. Several analyses from different countries have shown a strong correlation between hospital volume and postoperative mortality. Data from countries in which esophageal surgery has been centralized indicate beneficial effects of a centralized health care system on postoperative mortality after esophagectomy. Additionally, only high-volume centers generally provide optimal preoperative and postoperative management and comprehensive access to modern multimodal treatment. In Germany, esophageal surgery is still decentralized, but hospitals performing complex esophageal procedures have to fulfill minimum caseload requirements of 10 cases per year. In practice, these requirements are not met by the majority of hospitals and a detrimental effect on the achieved surgical outcomes can be noted. Therefore, we conclude that structural quality assurance is crucial to further reduce postoperative morbidity after esophageal surgery and to improve long-term results.


Development of an industrial cyber-physical platform for small series production using digital twins.
The article describes an industrial cyber-physical platform for small series production using digital twins under development at ITMO University (Saint Petersburg, Russia). The platform is based on the following approaches: group technology, adaptive and selective assembling, and digital twin of production systems and processes. The article presents a mechanism for constructing a unified manufacturing process, and results of an integrated multiscale simulation of an injection moulding process. The issues of ensuring identification and monitoring of objects of the industrial cyber-physical platform are considered. Specific service applications required to implement the smart product concept are discussed. The combination of the considered technologies is used to create digital twins of production system objects. All humans that have different roles in the product value stream can interact with the industrial cyber-physical platform at the three levels, receiving support in performing their tasks. This article is part of the theme issue 'Towards symbiotic autonomous systems'.


Modulatory effect of tropisetron in the liver of streptozotocin-induced diabetes in rats: biochemical and histological evidence.
Objectives There is an association between diabetes and liver disorders. Oxidative stress plays a crucial role in the pathology of hepatic abnormalities in diabetes. In this study, the effect of Tropisetron on the oxidative damage and histological alterations in the liver of type 1 diabetes mellitus (DM) were evaluated. Methods Thiry-five male Wistar rats were randomly divided into five experimental groups (n = 7): control (C), tropisetron (T), diabetes (D), diabetes + tropisetron (D + T) and diabetes + glibenclamide (D + G). A single injection of streptozotocin (STZ, 50 mg/kg; i.p) was used to induce diabetes. Tropisetron (3 mg/kg; i.p), as a 5-HT3 receptor antagonist and glibenclamide (1 mg/kg; i.p), as a positive control were given once daily for 2 weeks. Finally, animals were euthanized and liver samples were obtained for histopathological examination and biochemical measurements including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) levels. Results There is a significant increase in MDA (p < 0.001) level and a significant decrease (p < 0.001) in SOD and GPx contents in diabetic animals. Tropisetron attenuated MDA levels (p < 0.001) and enhanced SOD (p < 0.05) and GPx (p < 0.01) activities accompanied by histopathological improvement in the diabetes liver. Similar results were achieved in the rats treated with the standard drug, namely: glibenclamide. Conclusions Our findings indicate that tropisetron mitigates liver damage in the diabetes rats in part by attenuation of oxidative stress.


Supported gold nanoparticle-catalyzed hydration of alkynes under basic conditions.
TiO2-supported nanosize gold particles catalyze the hydration of alkynes using morpholine as a basic cocatalyst. Unlike most homogeneous cationic gold catalysts, the TiO2-Au/morpholine system is weakly basic and is compatible with acid-sensitive functional groups (e.g., silyl ethers, ketals) or with a strongly coordinating group such as pyridine. What's more, this gold catalyst can be recycled by simple filtration and works well in flow reactors.


Structural properties of ribosomal protein L11 from Escherichia coli.
Protein L11 has been isolated from the large subunit of the E. coli ribosome under non-denaturing conditions and studied by proton magnetic resonance spectroscopy, limited proteolysis, and fluorescence and UV spectroscopy. The protein consists of two domains, a tightly-folded N-terminal part and a C-terminal half with an extended and loosely folded conformation. It is likely that the N-terminal domain is located on the surface of the subunit whereas the C-terminal part is buried within the ribosomal structure. The two tyrosines in the N-terminal region behave as solvent-exposed residues, in good agreement with iodination studies on L11 in situ. It appears probable that the central region of L11, in which the protease cleavages occur, plays an important part in structural and functional aspects.


Myocardial substrate utilization and left ventricular function in adriamycin cardiomyopathy.
We evaluated alterations of substrate utilization in a rat model of adriamycin cardiomyopathy with deteriorating left ventricular function. Rats were treated with adriamycin (2 mg/kg), once a week for 6, 8, 9 and 10 wk. Fluorine-18-F-deoxyglucose (18F-FDG) and 125I-beta-methyl-branched fatty acid (125I-BMIPP) were used as tracers of glucose and fatty acid metabolism and 99mTc-hexakis (2-methoxyisobutyl-isonitrile) (99mTc-MIBI) was used as a myocardial blood flow tracer. Left ventricular ejection fraction (LVEF) calculated from gated blood pool images was used as an indicator of cardiac function. LVEF was normal in the 6-wk group (78.0% +/- 4.8%), abruptly decreased in the 8-wk group (43.1% +/- 10.1%) and further deteriorated in the 9-wk group (27.6% +/- 13.4%). Accumulation of 18F-FDG (%kgID/g) in the hearts of adriamycin treated animals progressively decreased compared to controls (2.19% +/- 0.38%); 1.47% +/- 0.42% (p < 0.01) at 6 wk, 1.22% +/- 0.27% (p < 0.001) at 8 wk, 0.69% +/- 0.56% (p < 0.001) at 9 wk and 0.50% +/- 0.08% (p < 0.001) at 10 wk. This decrease occurred earlier than the deterioration in LVEF. Myocardial accumulation of 125I-BMIPP decreased in the advanced stages of adriamycin cardiomyopathy and was well correlated with the decrease in 18F-FDG accumulation. However, the decrease was less profound than for 18F-FDG; 53.7% +/- 9.8% versus 31.6% +/- 25.4% of control at 9 wk (p = NS), 49.5% +/- 15.3% versus 22.6% +/- 3.5% of control at 10 wk (p < 0.05). Accumulation of 99mTc-MIBI did not differ between controls and the adriamycin treated groups. There were no differences in blood glucose levels between controls and adriamycin treatment groups. Both glucose and fatty acid utilization are decreased in adriamycin-induced cardiomyopathy and these critical impairments in energy metabolism are associated with heart failure. Impaired myocardial glucose utilization measured with 18F-FDG may be a particularly sensitive marker of adriamycin cardiomyopathy.


[Study on diarrhea disease caused by enterohemorrhagic Escherichia coli O157:H7 in Xuzhou city, Jiangsu province in 2000].
To investigate the proportion of hemorrhagic colitis (HC) caused by Escherichia coli O157:H7 in bacterial diarrhea in Xuzhou city, Jiangsu province. All stool samples from patients with diarrhea were screened for O157 antigen, using Immuno-gold kits. Positive samples were cultured to detect the existence of pathogens. All of the HC patients confirmed by bacterial isolation and identification were investigated for clinical symptoms and laboratory tests. Of the diarrhea patients identified in Feng county in May, and in Tongshan county of Xuzhou city in June 2000, Jiangsu province 0.98% and 5.89% were caused by Escherichia coli O157:H7 respectively, confirmed by bacteriological isolation and identification of stool samples. At the early phase of hemorrhagic colitis, 18.5% patients had at least one abnormal clinical laboratory test results including protein in urea and increased BUN or creatinine that indicating the possibility of kidney damage. In 27 strains of E. coli O157:H7 isolated from those patients, 13 and 14 were identified as Shiga toxin producing and Shiga-toxin negative E. coli O157:H7 (Stx-positive or Stx-negative) respectively. By analysis of the two groups of patients divided by according to the nature of Shiga toxin, four of 13 patients of Stx-positive group showed positive urea protein. However only 1 of the 13 patients of Stx-negative group was urea protein positive. The decreased Platelets counts were observed in 6 of 13 patients with Stx-positive group, but only in 1 of 14 patients with stx-negative group. These differences were statistically significant. HC patients caused by E. coli O157:H7 were commonly seen (up to 5.89%) in Xuzhou city, Jiangsu province. Early laboratory tests should be conducted for HC patients as early as possible in order to find early indictor of kidney failure which was critical for prevention of hemolytic uremic syndrome.


Human calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D.
The calcium-sensing receptor (CASR), expressed in parathyroid chief cells, thyroid C-cells, and cells of the kidney tubule, is essential for maintenance of calcium homeostasis. Here we show parathyroid, thyroid, and kidney CASR mRNA levels increased 2-fold at 15 h after intraperitoneal injection of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in rats. Human thyroid C-cell (TT) and kidney proximal tubule cell (HKC) CASR gene transcription increased approximately 2-fold at 8 and 12 h after 1,25(OH)2D3 treatment. The human CASR gene has two promoters yielding alternative transcripts containing either exon 1A or exon 1B 5'-untranslated region sequences that splice to exon 2 some 242 bp before the ATG translation start site. Transcriptional start sites were identified in parathyroid gland and TT cells; that for promoter P1 lies 27 bp downstream of a TATA box, whereas that for promoter P2, which lacks a TATA box, lies in a GC-rich region. In HKC cells, transcriptional activity of a P1 reporter gene construct was 11-fold and of P2 was 33-fold above basal levels. 10(-8) m 1,25(OH)2D3 stimulated P1 activity 2-fold and P2 activity 2.5-fold. Vitamin D response elements (VDREs), in which half-sites (6 bp) are separated by three nucleotides, were identified in both promoters and shown to confer 1,25(OH)2D3 responsiveness to a heterologous promoter. This responsiveness was lost when the VDREs were mutated. In electrophoretic mobility shift assays with either in vitro transcribed/translated vitamin D receptor and retinoid X receptor-alpha, or HKC nuclear extract, specific protein-DNA complexes were formed in the presence of 1,25(OH)2D3 on oligonucleotides representing the P1 and P2 VDREs. In summary, functional VDREs have been identified in the CASR gene and provide the mechanism whereby 1,25(OH)2D up-regulates parathyroid, thyroid C-cell, and kidney CASR expression.


Effect of topical fluoroquinolones on the expression of matrix metalloproteinases in the cornea.
Matrix metalloproteinases play an important role in extracellular matrix deposition and degradation. Based on previous clinical observations of corneal perforations during topical fluoroquinolone treatment, we decided to evaluate the comparative effects of various fluoroquinolone eye drops on the expression of matrix metalloproteinases (MMPs) in cornea. Eighty female Lewis rats were divided into two experimental groups: intact and wounded corneal epithelium. Uniform corneal epithelial defects were created in the right eye with application of 75% alcohol in the center of the tissue for 6 seconds. The treatment groups were tested as follows: 1) Tear drops: carboxymethylcellulose sodium 0.5 % (Refresh, Allergan); 2) Ciprofloxacin 0.3% (Ciloxan, Alcon); 3) Ofloxacin 0.3%(Ocuflox, Allergan); 4) Levofloxacin 0.5%(Quixin, Santen). Eye drops were administered 6 times a day for 48 hours. Rats were sacrificed at 48 hours. Immunohistochemical analysis and zymography were conducted using antibodies specific to MMPs-1, 2, 8 and 9. MMP-1, MMP-2, MMP-8 and MMP-9 expression were detected at 48 hrs in undebrided corneal epithelium groups treated with the topical fluoroquinolones. No statistical difference was observed in quantitative expression of MMPs among ciprofloxacin 0.3%, ofloxacin 0.3%, levofloxacin 0.5%. When the artificial tear group and the fluoroquinolone groups with corneal epithelial defect were compared, increased expression of MMPs was observed as a result of the wound healing process. However, the fluoroquinolone treated group exhibited high statistically significantly levels of MMPs expression. Our study provides preliminary evidence that topical application of fluoroquinolone drugs can induce the expression of MMP-1, MMP-2, MMP-8 and MMP-9 in the undebrided corneal epithelium compared to artificial tear eye drops.


Vaginal toxicity after high-dose-rate endovaginal brachytherapy: 20 years of results.
To evaluate vaginal toxicity (primary endpoint) and local control (secondary endpoint) in patients with endometrial cancer who underwent primary surgery and adjuvant high-dose-rate (HDR) endovaginal brachytherapy (BT). In September 2017, the authors conducted a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus, and Cochrane library. In this systematic review, the authors included randomized trials, non-randomized trials, prospective studies, retrospective studies, and cases. The time period of the research included articles published from September 1997 to September 2017. Acute endovaginal toxicity occurred in less than 20.6% and all acute toxicities were G1-G2. The most common early side effects due to HDR-BT treatment were vaginal inflammation, vaginal irritation, dryness, discharge, soreness, swelling, and fungal infection. G1-G2 late toxicity occurred in less than 27.7%. Finally, G3-G4 late vaginal occurred in less than 2%. The most common late side effects consisted of vaginal discharge, dryness, itching, bleeding, fibrosis, telangiectasias, stenosis, short or narrow vagina, and dyspareunia. The data suggest that HDR endovaginal brachytherapy, with or without chemotherapy, is very well tolerated with low rates of acute and late vaginal toxicities. Further prospective studies with higher numbers of patients and longer follow-up are necessary to evaluate acute and late toxicities after HDR endovaginal brachytherapy.


Tanshinone I suppresses growth and invasion of human breast cancer cells, MDA-MB-231, through regulation of adhesion molecules.
The role of cell adhesion molecules has been studied extensively in the process of inflammation, and these molecules are critical components of carcinogenesis and cancer metastasis. This study investigated the effect of tanshinone I derived from the traditional herbal medicine, Salvia miltiorrhiza Bunge, on the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells. Furthermore, this study investigated the effect of tanshinone I on cancer growth, invasion and angiogenesis on human breast cancer cells MDA-MB-231, both in vitro and in vivo. Tanshinone I dose dependently inhibited ICAM-1 and VCAM-1 expressions in human umbilical vein endothelial cells (HUVECs) that were stimulated with TNF-alpha for 6 h. Pretreatment with tanshinone I significantly reduced adhesion of either monocyte U937 or MDA-MB-231 cells to HUVECs. Interestingly, the inhibitory effect of tanshinone I on monocyte and cancer cell adhesion to HUVECs was mimicked by transfection with ICAM-1 and VCAM-1 small interfering RNA. In addition, tanshinone I effectively inhibited TNF-alpha-induced production of vascular endothelial growth factor (VEGF) and VEGF-mediated tube formation in HUVECs. Tanshinone I also inhibited TNF-alpha-induced VEGF production in MDA-MB-231 cells and migration of MDA-MB-231 cells through extracellular matrix. Additionally, reduction of tumor mass volume and decrease of metastasis incidents by tanshinone I were observed in vivo. In conclusion, this study provides a potential mechanism for the anticancer effect of tanshinone I on breast cancer cells, suggesting that tanshinone I may serve as an effective drug for the treatment of breast cancer.


Feasibility of Percutaneous Lumbar Discectomy Combined with Percutaneous Cementoplasty for Symptomatic Lumbar Disc Herniation with Modic Type I Endplate Changes.
Treatment of symptomatic lumbar disc herniation with Modic type I endplate changes is complex and challenging, requiring systemic and local therapies which include conservative therapy, epidural infiltrations, percutaneous therapeutic techniques, and surgical options. The clinical management of symptomatic lumbar disc herniation involving Modic type I endplate changes is uniquely challenging because it requires alleviating pain caused by both the herniated disc and the endplate osteochondritis. Through different approaches, percutaneous lumbar discectomy (PLD) and percutaneous cementoplasty (PCP) have been introduced into clinical practice as alternatives to traditional surgical and radiotherapy treatments of symptomatic lumbar disc herniation and other spine diseases. To evaluate the feasibility of PLD and PCP for symptomatic lumbar disc herniation with Modic type I endplate changes. PLD and PCP in 7 patients with symptomatic lumbar disc herniation with Modic type I endplate changes and its clinical effects were retrospectively evaluated. This study was conducted by an interventional therapy group at a medical center in a major Chinese city. Seven consecutive patients (2 men, 5 women; median age, 74.14 ± 5.34 years; age range, 68 - 82 years) who underwent percutaneous lumbar discectomy and cementoplasty for the treatment of symptomatic lumbar disc herniation with Modic type I changes between May 2013 and August 2015 were retrospectively analyzed. The MacNab Criteria, visual analog scale (VAS), and Oswestry Disability Index (ODI) for pain were assessed before and one week, 6 months, and one year after the procedure. Furthermore, the procedure duration, hospital stay length, and complications were assessed. The VAS of the back and leg decreased from 6.14 ± 0.69 (range, 5 - 7) and 7.29 ± 0.76 (range, 6 - 8) preoperatively to 2.29 ± 1.38 (range, 1 - 5) and 2.71 ± 0.60 (range, 1 - 6) one week, 1.86 ± 0.69 (range, 1 - 3) and 2.00 ± 0.58 (range, 1 - 3) 6 months, and 1.71 ± 0.76 (range, 1 - 3) and 1.85 ± 0.69 (range, 1 - 3) one year postoperatively. The ODI dropped from 76.86 ± 7.45 (range, 70 - 82) preoperatively to 26.29 ± 19.47 (range, 16 - 70) one week, 19.14 ± 2.79 (range, 16 - 24) 6 months, and 18.57 ± 2.99 (range, 16 - 24) one year postoperatively. The mean procedure duration was 55.71 ± 6.07 minutes (range, 50 - 65 minutes). The average length of hospital stay was 7.57 ± 1.27 days (range, 6 - 10 days). No obvious complications were noted. This was a retrospective study with a relatively small sample size. PLD plus PCP is a feasible technique for symptomatic lumbar disc herniation with Modic type I endplate changes.


Comparison of the Predictive Power of a Combination versus Individual Biomarker Testing in Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors.
Since tumor mutational burden (TMB) and gene expression profiling (GEP) have complementary effects, they may have improved predictive power when used in combination. Here, we investigated the ability of TMB and GEP to predict the immunotherapy response in patients with non-small cell lung cancer (NSCLC) and assessed if this combination can improve predictive power compared to that when used individually. This retrospective cohort study included 30 patients with NSCLC who received immune checkpoint inhibitors (ICI) therapy at the Seoul National University Bundang Hospital. programmed cell death-ligand-1 (PD-L1) protein expression was assessed using immunohistochemistry, and TMB was measured by targeted deep sequencing. Gene expression was determined using NanoString nCounter analysis for the PanCancer IO360 panel, and enrichment analysis were performed. Eleven patients (36.7%) showed a durable clinical benefit (DCB), whereas 19 (63.3%) showed no durable benefit (NDB). TMB and enrichment scores (ES) showed significant differences between the DCB and NDB groups (p=0.044 and p=0.017, respectively); however, no significant correlations were observed among TMB, ES, and PD-L1. ES was the best single biomarker for predicting DCB (area under the curve [AUC], 0.794), followed by TMB (AUC, 0.679) and PD-L1 (AUC, 0.622). TMB and ES showed the highest AUC (0.837) among other combinations (AUC [TMB and PD-L1], 0.777; AUC [PD-L1 and ES], 0.763) and was similar to that of all biomarkers used together (0.832). The combination of TMB and ES may be an effective predictive tool to identify patients with NSCLC patients who would possibly benefit from ICI therapies.


Bioengineering the Cardiac Conduction System: Advances in Cellular, Gene, and Tissue Engineering for Heart Rhythm Regeneration.
Heart rhythm disturbances caused by different etiologies may affect pediatric and adult patients with life-threatening consequences. When pharmacological therapy is ineffective in treating the disturbances, the implantation of electronic devices to control and/or restore normal heart pacing is a unique clinical management option. Although these artificial devices are life-saving, they display many limitations; not least, they do not have any capability to adapt to somatic growth or respond to neuroautonomic physiological changes. A biological pacemaker could offer a new clinical solution for restoring heart rhythms in the conditions of disorder in the cardiac conduction system. Several experimental approaches, such as cell-based, gene-based approaches, and the combination of both, for the generation of biological pacemakers are currently established and widely studied. Pacemaker bioengineering is also emerging as a technology to regenerate nodal tissues. This review analyzes and summarizes the strategies applied so far for the development of biological pacemakers, and discusses current translational challenges toward the first-in-human clinical application.


[How to establish the hospital information system security policies].
It is important to establish the hospital information system security policies. While these security policies are being established, a comprehensive consideration should be given to the acceptable levels of users, IT supporters and hospital managers. We should have a formal policy designing process that is consistently followed by all security policies. Reasons for establishing the security policies and their coverage and applicable objects should be stated clearly. Besides, each policy should define user's responsibilities and penalties of violation. Every organization will need some key policies, such as of information sources usage, remote access, information protection, perimeter security, and baseline host/device security. Security managing procedures are the mechanisms to enforce the policies. An incident-handling procedure is the most important security managing procedure for all organizations.


Collision tumor of the rectum: a case report of metastatic gastric adenocarcinoma plus primary rectal adenocarcinoma.
Collision tumors are thought to arise from the accidental meeting and interpenetration of two independent tumors. We report here a highly unusual case of a 61-year old man who had a unique tumor that was composed of a metastatic adenocarcinoma from the stomach to the rectum, which harbored a collision tumor of primary rectal adenocarcinoma. The clonalities of the two histologically distinct lesions of the rectal mass were confirmed by immunohistochemical and molecular analysis. Although histologic examination is the cornerstone in pathology, immunohistochemical and molecular analysis can provide evidence regarding whether tumors originate from the same clone or different clones. To the best of our knowledge, this is the first reported case of such an occurrence.


[Anesthetic management using HemoSonic 100 in a patient with chronic renal failure and dilated cardiomyopathy].
Anesthetic management for nephrectomy using HemoSonic 100, was performed in a patient with chronic renal failure and dilated cardiomyopathy (DCM). Anesthesia was induced and maintained with infusion of propofol and ketamine, and intermittent administration of fentanyl. During the surgery left ventricular ejection time (LVETc) decreased due to active bleeding from the renal artery. LVETc provided useful information for adequate preload and rate of transfusion in this case. Anesthesia and operation were finished successfully with relatively stable circulatory condition. We conclude that HemoSonic 100 is a useful monitor in anesthetic management of a patient with DCM, especially for the assessment of adequate preload.


Analysis of the in vivo decay of the Escherichia coli dicistronic pyrF-orfF transcript: evidence for multiple degradation pathways.
Messenger RNA decay in Escherichia coli is slowed in pnp-7 (PNPase) rnb-500 (RNase II) rne-1(RNase E) multiple mutants. We have used Northern blots, S1 nuclease protection and primer extension analysis to map 18 endonucleolytic cleavage sites within the pyrF-orfF dicistronic transcript. Although examination of a total of 27 cleavage sites including those determined for the monocistronic trxA transcript revealed a complex pattern, the central four nucleotides within a cluster of 12 residues encompassing the cleavage sites showed a definite A/U preference. Also of interest was the processing of the dicistronic transcript to remove the downstream orfF sequence as a stable but untranslated RNA fragment. The data provide further support for the hypothesis that multiple decay pathways are involved in the decay of a single transcript. In particular, the pyrF-orfF transcript apparently can be degraded either in the 5' to 3' or the 3' to 5' direction. Our results are discussed in light of current models of mRNA decay involving polyadenylation and multiprotein decay complexes.


Fibroblast growth factor receptor 1 oncogene partner as a novel prognostic biomarker and therapeutic target for lung cancer.
To screen candidate molecules that might be useful as diagnostic biomarkers or for development of novel molecular-targeting therapies, we previously carried out gene-expression profile analysis of 101 lung carcinomas and detected an elevated expression of FGFR1OP (fibroblast growth factor receptor 1 oncogene partner) in the majority of lung cancers. Immunohistochemical staining using tumor tissue microarrays consisting of 372 archived non-small cell lung cancer (NSCLC) specimens revealed positive staining of FGFR1OP in 334 (89.8%) of 372 NSCLCs. We also found that the high level of FGFR1OP expression was significantly associated with shorter tumor-specific survival times (P < 0.0001 by log-rank test). Moreover, multivariate analysis determined that FGFR1OP was an independent prognostic factor for surgically treated NSCLC patients (P < 0.0001). Treatment of lung cancer cells, in which endogenous FGFR1OP was overexpressed, using FGFR1OP siRNA, suppressed its expression and resulted in inhibition of the cell growth. Furthermore, induction of FGFR1OP increased the cellular motility and growth-promoting activity of mammalian cells. To investigate its function, we searched for FGFR1OP-interacting proteins in lung cancer cells and identified ABL1 (Abelson murine leukemia viral oncogene homolog 1) and WRNIP1 (Werner helicase interacting protein 1), which was known to be involved in cell cycle progression. FGFR1OP significantly reduced ABL1-dependent phosphorylation of WRNIP1 and resulted in the promotion of cell cycle progression. Because our data imply that FGFR1OP is likely to play a significant role in lung cancer growth and progression, FGFR1OP should be useful as a prognostic biomarker and probably as a therapeutic target for lung cancer.


Carboxy terminal domain of the largest subunit of RNA polymerase II of Leishmania donovani has an unusually low number of phosphorylation sites.
The C-terminal domain (CTD) of the largest subunit of RNA polymerase II in higher eukaryotes has an altered form in Leishmania donovani. To determine whether this is a general feature of the kinetoplastida and to investigate the role of this domain in parasitic RNA pol II transcription, we isolated the gene encoding RNA pol II LS (rpolIILS) and analyzed its C-terminal domain. The discreteness observed may be due to a functional constraint delineating parasite from host. The gene for L. donovani rpolIILS was picked up and sequenced. The CTD of L. donovani rpolIILS was purified as a His-tagged recombinant protein and phosphorylated with a crude kinase extract from L. donovani. An immunoblot analysis of the phosphorylated CTD and photo-crosslinked L. donovani nuclear extracts was done using anti-CTD antibody. The L. donovani rpolIILS is encoded by a single-copy gene. Its transcript is matured postranscriptionally, with the mini-exon trans-spliced 397 bases upstream of the initiation site. The uniqueness of Leishmania rpolIILS CTD according to prediction analysis was corroborated with in vitro phosphorylation of the recombinant protein. Photoaffinity labelling of L. donovani nuclear run-on transcripts and immunoblot analysis using anti-CTD antibody could identify the active form of RNA polymerase II enzyme in this parasite. The L. donovani rpolIILS possesses a unique C-terminal extension lacking the characteristic repeats but containing serine residues as a potential phosphorylation site. Anti-CTD antibody could recognize a single molecular species for the RNA pol II enzyme in L. donovani.


Evolution of the pineal complex: correlation of structure and function.
The pineal organ is a derivative and integral component of the brain. In phylogeny it has changed from a 'third eye' capable of direct achromatic and/or chromatic responses to light to an endocrine gland influenced by visual stimuli from the retina. The outer segment of pineal photoreceptors contains a microspectrophotometrically detectable photopigment and an opsin-immunoreactive protein. Certain pinealocytes endowed with an outer segment display fluorophores of 5-HT/HTP and can be regarded as photoneuroendocrine cells. These photoneuroendocrine cells resemble cerebrospinal fluid-contacting neurons. The intrinsic circuitry (wiring diagram) of pineal photoreceptor organs has been only partly deciphered ; this holds true also for the neurotransmitters and synaptic patterns. Pineal photoreceptor organs are connected to the brain, i.e., to habenular, pretectal, thalamic, tegmental (reticular), and hypothalamic centers. The special anatomical and physiological features of the pineal organ enable it to translate photic information into neural and neuroendocrine responses.


High-throughput gene and SNP discovery in Eucalyptus grandis, an uncharacterized genome.
Benefits from high-throughput sequencing using 454 pyrosequencing technology may be most apparent for species with high societal or economic value but few genomic resources. Rapid means of gene sequence and SNP discovery using this novel sequencing technology provide a set of baseline tools for genome-level research. However, it is questionable how effective the sequencing of large numbers of short reads for species with essentially no prior gene sequence information will support contig assemblies and sequence annotation. With the purpose of generating the first broad survey of gene sequences in Eucalyptus grandis, the most widely planted hardwood tree species, we used 454 technology to sequence and assemble 148 Mbp of expressed sequences (EST). EST sequences were generated from a normalized cDNA pool comprised of multiple tissues and genotypes, promoting discovery of homologues to almost half of Arabidopsis genes, and a comprehensive survey of allelic variation in the transcriptome. By aligning the sequencing reads from multiple genotypes we detected 23,742 SNPs, 83% of which were validated in a sample. Genome-wide nucleotide diversity was estimated for 2,392 contigs using a modified theta (theta) parameter, adapted for measuring genetic diversity from polymorphisms detected by randomly sequencing a multi-genotype cDNA pool. Diversity estimates in non-synonymous nucleotides were on average 4x smaller than in synonymous, suggesting purifying selection. Non-synonymous to synonymous substitutions (Ka/Ks) among 2,001 contigs averaged 0.30 and was skewed to the right, further supporting that most genes are under purifying selection. Comparison of these estimates among contigs identified major functional classes of genes under purifying and diversifying selection in agreement with previous researches. In providing an abundance of foundational transcript sequences where limited prior genomic information existed, this work created part of the foundation for the annotation of the E. grandis genome that is being sequenced by the US Department of Energy. In addition we demonstrated that SNPs sampled in large-scale with 454 pyrosequencing can be used to detect evolutionary signatures among genes, providing one of the first genome-wide assessments of nucleotide diversity and Ka/Ks for a non-model plant species.


Thermodynamics constrains the evolution of insect population growth rates: "warmer is better".
Diverse biochemical and physiological adaptations enable different species of ectotherms to survive and reproduce in very different temperature regimes, but whether these adaptations fully compensate for the thermodynamically depressing effects of low temperature on rates of biological processes is debated. If such adaptations are fully compensatory, then temperature-dependent processes (e.g., digestion rate, population growth rate) of cold-adapted species will match those of warm-adapted species when each is measured at its own optimal temperature. Here we show that cold-adapted insect species have much lower maximum rates of population growth than do warm-adapted species, even when we control for phylogenetic relatedness. This pattern also holds when we use a structural-equation model to analyze alternative hypotheses that might otherwise explain this correlation. Thus, although physiological adaptations enable some insects to survive and reproduce at low temperatures, these adaptations do not overcome the "tyranny" of thermodynamics, at least for rates of population increase. Indeed, the sensitivity of population growth rates of insects to temperature is even greater than predicted by a recent thermodynamic model. Our findings suggest that adaptation to temperature inevitably alters the population dynamics of insects. This result has broad evolutionary and ecological consequences.


Haploidentical Transplant in Radiosensitive Severe Combined Immunodeficiency Disease.
Severe combined immunodeficiency (SCID) is an inborn error of immunity invariably resulting in mortality in infancy until managed by hematopoietic stem cell transplant (HSCT). We present an unusual case of SCID with a rare mutation involving the non-homologous end-joining 1 (NHEJ1) gene, where a haploidentical HSCT was carried out with modified conditioning and graft versus host prophylaxis regimen using proteasome inhibitor bortezomib with a successful outcome.


Generating CNS organoids from human induced pluripotent stem cells for modeling neurological disorders.
Understanding human brain development and disease is largely hampered by the relative inaccessibility of human brain tissues. Recent advances in human induced pluripotent stem cells (hiPSCs) have led to the generation of unlimited human neural cells and thereby facilitate the investigation of human brain development and pathology. Compared with traditional 2-dimensional (2D) culture methods, culturing the hiPSC-derived neural cells in a three-dimensional (3D) free-floating manner generates human central nervous system (CNS) organoids. These 3D CNS organoids possess the unique advantage of recapitulating multi-regional or region-specific cytoarchitecture seen in the early human fetal brain development. The CNS organoids are becoming a strong complement to the animal model in studying brain development and pathology, and developing new therapies to treat neurodevelopmental diseases. Further improvements to the long-term maintenance and neural maturation of the organoids may allow them to model neurodegenerative diseases. In this review, we will summarize the current development of hiPSCs to generate CNS organoids for modeling neurological disorders and future perspective.


Role of JAK/STAT pathway in IL-6-induced activation of vascular smooth muscle cells.
IL-6, an inducer of the acute-phase response, is linked with the development of vascular disease and atherosclerosis. One mechanism likely involves direct effects of IL-6 on vascular smooth muscle cells (VSMC), for IL-6 can induce VSMC proliferation and the release of monocyte chemoattractant protein-1 (MCP-1). We hypothesized that this stimulation occurs via the JAK (janus-activated kinase)/STAT (signal and transducers and activators of transcription) signaling pathway. Rat VSMC were stimulated with IL-6 in the presence or absence of a JAK 2 inhibitor, and the activation of STAT 3 (by Western), MCP-1 (by ELISA) and DNA synthesis (by (3)H-thymidine incorporation) was determined. IL-6 rapidly induced phosphorylation of STAT 3 in a dose- and time-dependent manner with a peak expression at 30 min. IL-6 also stimulated MCP-1 protein production and DNA synthesis dose dependently. 50 microM of AG490, a specific JAK 2 inhibitor, partially inhibited STAT 3 activation and MCP-1 production, with near complete inhibition of DNA synthesis. The JAK/STAT pathway partially mediates IL-6-induced MCP-1 production and DNA synthesis in rat VSMC. These studies implicate a role of the JAK/STAT pathway in the development of vascular disease and atherosclerosis.


Identification of potential CD8+ epitopes in pp62 polyprotein of African swine fever virus using computational immunology.
The highly infectious African swine fever virus (ASFV) is currently the only known DNA arbovirus within the Asfarviridae family which primarily infects domestic pigs and wild boars. African swine fever (ASF) leads to a mortality rate of up to 100% which has caused massive socio-economic losses worldwide. Previous research indicates that ASFV's virulence can be attributed to polyprotein pp62, which plays a crucial role in viral assembly and core maturation. This particular study utilized in silico analysis to identify highly conserved cytotoxic T-cell epitopes in pp62 that can potentially serve as key components for future ASFV vaccines. To achieve this, the researchers retrieved, clustered, and aligned the peptide sequences of pp62. Subsequently, the aligned sequences were analyzed to identify epitopes that bind promiscuously to the swine major histocompatibility complex I (MHC I) alleles and exhibiting MHC IC50 values < 500 nM. Additionally, peptide sequences with positive proteasome and TAP scores were considered. Potential cross-reactivity was assessed by comparing the peptide sequences against available proteome sequences of Sus scrofa domesticus in various databases. Furthermore, molecular docking was conducted to evaluate the binding of candidate epitopes with swine leukocyte antigen-1*0401 (SLA-1*0401). The dissociation constants, binding energies, root mean square deviation, and root mean square fluctuation values for the SLA-epitope complexes were compared with a positive reference. In the course of the study, 21 highly conserved CD8+ epitopes were identified, out of which four were further assessed for their potential immunogenicity. The results demonstrated that the highly conserved CD8+ epitopes discovered in this study are promising for integration into future ASFV vaccine formulations. As preliminary data, it is anticipated that these findings will subsequently undergo in vitro and in vivo studies in the future.


Decreased expression of SOX7 induces cell proliferation and invasion and correlates with poor prognosis in oral squamous cell carcinoma.
SOX7, a member of the SOX family of transcription factors, acts as a tumor suppressor in multiple cancers. Downregulation of SOX7 has been reported in advanced tumors and correlates with poor prognosis. The aims of this study were to investigate the effects of SOX7 on cell proliferation, invasion, and colony formation in oral squamous cell carcinoma (OSCC) cells and to evaluate the effectiveness of SOX7 protein as a prognostic indicator for OSCC patients. oral squamous cell carcinoma (OSCC) cell lines were treated with SOX7 small interfering RNA or SOX7 peptide, and their effects on cell proliferation, invasiveness, and colony formation were investigated by proliferation, in vitro invasion, and clonogenic assays. SOX7 protein expression in OSCC and normal oral mucosal tissues was examined by immunohistochemistry. Associations between SOX7 protein expression and clinicopathological parameters of OSCC patients were statistically analyzed. SOX7 silencing-induced cell proliferation and invasion in SCC-4 cells. SOX7 peptide treatment inhibited cell proliferation, colony formation, and invasion in SCC-9 and SCC-25 cells. Expression of SOX7 protein was decreased in OSCC tissues compared with normal oral mucosal tissues (P<.001). Negative SOX7 expression in patients with OSCC was significantly associated with positive lymph node metastasis (P=.041), advanced TNM stage (P=.024), and poor prognosis (P=.017). These results suggest that SOX7 inhibits cell proliferation, colony formation, and invasion in OSCC as a tumor suppressor and that negative SOX7 expression could be a poor prognostic indicator for patients with OSCC.


Molecular Dynamic Simulations and Molecular Docking as a Potential Way for Designed New Inhibitor Drug without Resistance.
Mycobacterium tuberculosis is the cause of tuberculosis in humans and is responsible for more than 2 million deaths per year. Despite the development of anti-tuberculosis drugs (Isoniazid, Rifampicin, Ethambutol, pyrazinamide, streptomycin, etc.) and the TB vaccine, this disease has claimed the lives of many people around the world. Drug resistance in this disease is increasing day by day. Conventional methods for discovering and developing drugs are usually time-consuming and expensive. Therefore, a better method is needed to identify, design, and manufacture TB drugs without drug resistance. Bioinformatics applications in obtaining new drugs at the structural level include studies of the mechanism of drug resistance, detection of drug interactions, and prediction of mutant protein structure. In the present study, computer-based approaches including molecular dynamics simulation and molecular docking as a novel and efficient method for the identification and investigation of new cases as well as the investigation of mutated proteins and compounds will be examined .


Fighting from the right side of the brain: left visual field preference during aggression in free-ranging male tree lizards (Urosaurus ornatus).
In a field study on male tree lizards (Urosaurus ornatus), we tested the hypothesis that aggression is lateralized, and predicted that resident males should preferentially use the left-visual field (LVF)/right hemisphere in aggressive interactions with other males. This prediction was based on results for a small but taxonomically diverse number of vertebrates indicating a left-eye preference/ right hemisphere specialization for aggression. Many lizards use postural displays to signal aggression and lateral eye placement prevents binocular vision of such displays. The fullshow is an aggressive display that is typically performed with the body held perpendicular to that of the opponent. We staged male-male encounters by introducing stimulus males to free-ranging males (hereafter called focal males), and then recorded both the focal male's behavior and the visual field that he used to view the intruder while performing fullshow displays. When intruders were introduced in the right visual field (RVF), focal males were equally likely to use either the LVF or RVF to perform their first fullshow. However, in these RVF introductions focal males were more likely to turn and use the LVF if the intruder was smaller. In contrast to RVF introductions, in LVF introductions focal males were significantly more likely than expected by chance to continue to use the LVF to view the intruder when performing the first fullshow. Furthermore, if focal males performed their first fullshow with the intruder in their LVF, they subsequently gave more aggressive displays than focal males that performed their first display with the intruder in their RVF. Additionally, charge (a highly aggressive behavior that usually leads to direct physical contact and a bite) was significantly more likely to occur while the LVF was being used to view the opponent. These results are consistent with the hypothesis that aggression is lateralized to the right hemisphere. This study is one of only a few examples of laterality of brain function demonstrated in a free-ranging vertebrate.


The effect of streptokinase on intramyocardial hemorrhage, infarct size, and the no-reflow phenomenon during coronary reperfusion.
The purpose of this study was to determine whether streptokinase exacerbates intramyocardial hemorrhage during coronary reperfusion, has any intrinsic effect on myocardial infarct size other than its ability to lyse proximal thrombi in coronary arteries, and can abolish the no-reflow phenomenon. Anesthetized open-chest dogs underwent coronary occlusion for 3 hr followed by 3 hr of reperfusion. Area of infarct was assessed by tetrazolium staining, anatomic zone of no-reflow by injection of the fluorescent dye thioflavin S at the end of the reperfusion period, regional blood flow during occlusion and reperfusion by the radioactive microsphere technique, and extent of gross hemorrhage by assessment of photographic enlargements of the heart slices. Area of infarction of the left ventricle was similar in control (13.4 +/- 3.6%) and streptokinase-treated dogs (13.0 +/- 2.9%; p = NS). Seven of eight dogs in the untreated group had anatomic perfusion defects as assessed by thioflavin S at the end of the reperfusion phase; seven of eight dogs in the streptokinase group had anatomic perfusion defects. There was no difference in the extent of gross hemorrhage between the two groups (6.5 +/- 2.1% of left ventricle in controls and 5.7 +/- 2.3% in streptokinase-treated dogs). Severe depression of regional blood flow during reperfusion was present within the infarcted tissue and was associated with an anatomic perfusion defect as defined by thioflavin S; there was moderate depression of flow within the noninfarcted, salvaged subepicardium. In a separate series of experiments, infarcts were assessed for hemoglobin content. Intramyocardial hemoglobin levels were not higher after fibrinolytic therapy plus reperfusion compared with reperfusion alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Exploring geomasking methods for geoprivacy: a pilot study in an environment with built features.
This study discusses the ethical use of geographical information systems (GIS) data with a focus on geomasking for upholding locational privacy. As part of a pilot study in Jeddah City, Saudi Arabia, we used open-source geomasking methods to ensure geoprivacy while examining built environment features that determine the quality of life among individuals with type-II diabetes. We employed the open-source algorithms Maskmy.XYZ and NRand-k for geomasking 329 data points. The results showed no differences between global and city-level spatial patterns, but significant variations were observed with respect to local patterns. These findings indicate the promising potential of the chosen geomasking technologies with respect to ensuring locational privacy but it was noted that further improvements are needed. We recommend developing enhanced algorithms and conducting additional studies to minimize any negative impact of geomasking in spatial analysis with the overall aim of achieving a better understanding of ethical considerations in GIS sciences. In conclusion, application of geomasking is straightforward and can lead to enhanced use for privacy protection in geospatial data analysis.


Association Between Parafibromin Expression and Presence of Brown Tumors and Jaw Tumors in Patients with Primary Hyperparathyroidism: Series of Cases with Review of the Literature.
BACKGROUND Brown and jaw tumors are rare entities of poorly understood etiology that are regarded as end-stage of bone remodeling in patients with long-lasting and chronic hyperparathyroidism. Jaw tumors are mainly diagnosed in jaw tumors syndrome (HPT-JT syndrome) and are caused by mutation in the CDC73 gene, encoding parafibromin, a tumor suppressing protein. The aim of this work is to present 4 cases of patients in whom the genetic mutation of the CDC73 gene and clinical presentation coexist in an unusual setting that has not yet been described. CASE REPORT We present cases of 4 patients with primary hyperparathyroidism. Three were diagnosed with brown tumors (located in long bones, ribs, iliac, shoulders) and 1 with brown and jaw tumors. Expression of parafibromin in affected parathyroid tissues were analyzed. In patients without positive parafibromin staining, we searched for CDC73 mutation using next-generation sequencing. Parafibromin staining was positive in 1 patient with brown tumors and was negative in 2 individuals with brown tumors and 1 with brown and jaw tumors. CDC73 mutation was detected in two-thirds of patients (60%) with negative staining for parafibromin and brown tumors. MEN1 mutation was found in the patient with brown tumor and positive staining for parafibromin. CONCLUSIONS Patients with hyperparathyroidism and coexistence of brown tumors or jaw tumors might have decreased expression of parafibromin in parathyroid adenoma tissue, which might be caused by CDC73 mutation and suggest a genetic predisposition. Further research on much larger study groups is needed.


Use of a treatment algorithm to achieve NCEP ATP III goals with atorvastatin.
This multicenter, 8-week, single-step titration, open-label study sought to assess the percentage of subjects who achieved their National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III low-density lipoprotein (LDL)-cholesterol target when assigned a starting dose of atorvastatin (10 mg, 20 mg, 40 mg, or 80 mg) selected using an algorithm based on their 10-year CHD risk and the magnitude of LDL-cholesterol lowering necessary to reach goal. Following an 8-week washout period, 1298 subjects, categorized as low, medium, or high risk, were assigned to 4 weeks of treatment with a starting dose of atorvastatin selected by the algorithm. At week 4, subjects who did not achieve goal (15.8%) were titrated to the next-higher dose. The primary endpoint was the percentage of subjects in each risk group who achieved LDL-cholesterol goal at week 8. At 8 weeks, 84.8% of subjects (low risk 92.9%; moderate risk 84.0%; high risk 81.1%) achieved LDL-cholesterol target. The majority of patients (84.2%) achieved their lipid target through the use of the algorithm-based starting dose (10-80 mg) without the need for titration. No patient had elevations in creatine phosphokinase >10 times the upper limit of normal. Elevations in alanine aminotransaminase or aspartate aminotransaminase were observed in <1% of study subjects and were unrelated to dose. Selecting the starting dose of atorvastatin using a treatment algorithm achieves NCEP ATP III LDL-cholesterol goals in the majority of patients and minimizes the need for dose titration.


Neuropathology and apolipoprotein E profile of aged chimpanzees: implications for Alzheimer disease.
Neuropathological findings in three aged chimpanzees were compared with those in rhesus monkeys and individuals with Alzheimer disease. Senile plaques and blood vessels were immunoreactive for amyloid beta-protein and apolipoprotein E (apoE) in the nonhuman primates, recapitulating findings in human aging and Alzheimer disease. Neurofibrillary tangles, another hallmark of Alzheimer disease, were absent. PCR/restriction-enzyme analysis in chimpanzees revealed an APOE profile similar to the human APOE type 4 allele associated with an increased risk of Alzheimer disease. These findings militate against the hypothesis that the absence of APOE type 3 allele predisposes to neurofibrillary tangle formation and support the value of aged primates for exploring mechanisms of amyloid processing and the role of apoE.


Vaccinia virus evasion of regulated cell death.
Regulated cell death is a powerful anti-viral mechanism capable of aborting the virus replicative cycle and alerting neighbouring cells to the threat of infection. The biological importance of regulated cell death is illustrated by the rich repertoire of host signalling cascades causing cell death and by the multiple strategies exhibited by viruses to block death signal transduction and preserve cell viability. Vaccinia virus (VACV), a poxvirus and the vaccine used to eradicate smallpox, encodes multiple proteins that interfere with apoptotic, necroptotic and pyroptotic signalling. Here the current knowledge on cell death pathways and how VACV proteins interact with them is reviewed. Studying the mechanisms evolved by VACV to counteract host programmed cell death has implications for its successful use as a vector for vaccination and as an oncolytic agent against cancer.


Significance of data treatment and experimental setup on the determination of copper complexing parameters by anodic stripping voltammetry.
Different procedures of voltammetric peak intensities determination, as well as various experimental setups were systematically tested on simulated and real experimental data in order to identify critical points in the determination of copper complexation parameters (ligand concentration and conditional stability constant) by anodic stripping voltammetry (ASV). Varieties of titration data sets (Cu(measured)vs. Cu(total)) were fitted by models encompassing discrete sites distribution of one-class and two-class of binding ligands (by PROSECE software). Examination of different procedures for peak intensities determination applied on voltammograms with known preset values revealed that tangent fit (TF) routine should be avoided, as for both simulated and experimental titration data it produced an additional class of strong ligand (actually not present). Peak intensities determination by fitting of the whole voltammogram was found to be the most appropriate, as it provided most reliable complexation parameters. Tests performed on real seawater samples under different experimental conditions revealed that in addition to importance of proper peak intensities determination, an accumulation time (control of the sensitivity) and an equilibration time needed for complete complexation of added copper during titration (control of complexation kinetics) are the keypoints to obtain reliable results free of artefacts. The consequence of overestimation and underestimation of complexing parameters is supported and illustrated by the example of free copper concentrations (the most bioavailable/toxic specie) calculated for all studied cases. Errors up to 80% of underestimation of free copper concentration and almost two orders of magnitude overestimation of conditional stability constant were registered for the simulated case with two ligands.


Smoking during pregnancy and plasma concentrations beta-carotene and alpha-tocopherol in the immediate postpartum period in Brazilian women.
This study investigated the relationship between plasma concentrations of beta-carotene and the alpha-tocopherol/lipid ratio, and smoking in 233 postpartum women, from July to November 2002, in the city of Joinville, Brazil. Thirty-seven percent (37%) of the women included in this study had low concentrations of alpha-tocopherol (< 11.63 micromol/L) and 61% of the women presented low concentrations of beta-carotene (< 0.39 micromol/L). Multivariate regression analysis investigated the relationship between smoking and the concentration of the vitamins, adjusting by confounding variables. The final regression model showed inverse associations between beta-carotene concentrations and smoking (p = 0.036), and beta-carotene concentrations and triglyceride levels (p = 0.021). There was an association between the plasma alpha-tocopherol/lipid ratio and per capita income (p = 0.003), but no association with smoking. We advise further studies to evaluate the impact of smoking and oxidative stress on the concentrations of these vitamins.


Synthesis of polyhydroxy piperidines and their analogues: a novel approach towards selective inhibitors of alpha-glucosidase.
Various polyhydroxy piperidine azasugars have been synthesized from precursors 18a and 18b, obtained in both enantiomeric forms from d-ribose. Out of these polyhydroxy piperidine azasugars, 22, 39 and 20 were found to be potent as well as selective inhibitors of alpha-glucosidase with K(i) values ranging as low as 1.07 microM, 16.4 microM, and 88.2 microM, respectively. Replacement of the hydroxy methylene moiety of (K(i) 33% at 1 mM) by an amino methylene moiety (32, K(i) 36.8 microM) showed a remarkable increase in the activity (almost 30 times). Furthermore, increasing the lipophilicity of by N-alkylation with a dodecyl group (36) showed a three-fold enhancement in the activity (K(i) 217 microM to K(i) 72.3 microM).


Indian egg donors' characteristics, motivations and feelings towards the recipient and resultant child.
This is the first study to examine characteristics, motivations and experiences of Indian egg donors. In-depth interviews were conducted with 25 egg donors who had donated during the previous 8 months at a fertility clinic in Mumbai. The semi-structured interviews were conducted in Hindi and English. In addition to demographic information, data were collected on donors' motivations for donating, with whom they had discussed donation, and feelings towards the recipients. The response rate was 66%. All participants were literate and had attended school. Twenty (80%) egg donors had children and five (20%) did not. The most common motivation (19, 76%) for donating was financial need. Egg donors had discussed their donation with their husband or with close family/friends, with almost all mentioning that wider society would disapprove. The majority (20, 80%) had no information about the recipients and 11 (44%) preferred not to. The findings highlight the similarities and differences between egg donors from India and those from other countries and that egg donors are of a more varied demographic background than surrogates in India. Given that India has been a popular destination for fertility treatment, the findings have important implications for regulation and practice within India and internationally.


[Lymphectomy in differentiated thyroid carcinoma].
Papillary and follicular thyroid carcinoma are still characterised by unclear biological and clinical behaviour with an autoptic incidence higher than the clinical incidence. Lymph-node involvement represents a prognostic factor that may increase the rate of local relapse, reducing long-term survival only in high risk patients--age > 45 years, M+, T > 3 cm, extra thyroidal extension, follicular histotype. The authors analyse the role of lymph-node cervical dissection. Routine or selective, extended or conservative lymphectomy are described in the literature. Prognostic factors are useful to determine the most appropriate surgical procedure. An elective cervical central dissection may be indicated in patients at high risk, while in cases of monolateral lymph-node metastases, in patients at low risk, a selective lymph node dissection of levels VI-III-IV is associated with lower morbidity. Modified radical neck dissection is reserved for patients at high risk or in cases of multiple lymph-node metastases (> 5) to reduce the incidence of local relapse. In the treatment of differentiated thyroid carcinoma an elective total thyroidectomy must be performed in combination with adjuvant radioiodine ablation.


Review of Speech Outcomes in Cochlear Implant Recipients at a Nascent Cochlear Implant Program.
The use of cochlear implantation to rehabilitate moderate to profound sensorineural hearing loss has become more widespread; however, the adult utilization rate of cochlear implant candidates is still very less. The study aims to examine the percentage of adult patients in a heterogeneous group of cochlear implant recipients at a nascent cochlear implant program who demonstrate improvements in speech outcomes. Speech outcome scores were assessed preoperatively and postoperatively at three, six, and 12-month intervals using consonant-nucleus-consonant (CNC) words and AzBio sentences in quiet. Mean speech outcome scores at each time point and binomial distribution tables with 95% CI were used to assess individual improvement in speech understanding. 45 patients underwent a total of 49 cochlear implantation surgeries. The mean age at surgery was 62 years. The mean preoperative CNC score in the ear to be implanted was 18%±18, while the mean postoperative CNC score at three, six, and 12 months was 35%±21, 44%±23, and 45%±25, respectively. The mean preoperative AzBio score in the ear to be implanted was 22%±26 while the mean postoperative AzBio score at three, six, and 12 months was 50%±29, 56%±27, and 63%±26, respectively. Of the implantations, 74% (32 of 43) and 69% (22 of 32) showed significant improvement at six months or one year using AzBio and CNC binomial distribution tables, respectively. Findings demonstrate significant improvements in speech perception following cochlear implantation for patients not benefiting from hearing aid aural rehabilitation. The study provides realistic expectations for new and emerging programs hoping to demonstrate cochlear implant utility for improving patients' speech outcomes.


[Neurotransmitter control of pupillary motoricity in man].
The pupillary responses to different agonists and antagonists of the sympathetic and parasympathetic systems have been studied in normal volunteers. The eyedrops were instilled unilaterally and the responses were evaluated by measuring the changes in diameter of the pupils (in millimeters). All the eyedrops induced an unilateral response on the instilled side. The mydriatic substances (phenylephrine, thropamide, tyramine) showed an evident and lasting action. Phenylephrine 1% was found to be a threshold dose to acquire the mydriatic effect. The beta blocking agent (timolol) induced a short mydriatic response, while methaproterenol did not change the pupillary diameter. Clonidine caused an unilateral mydriasis. The alpha blocking agent and the parasympathetic system stimulation agent induced miotic effects The results are discussed with particular reference to the possible mechanism of the pupillary response to timolol and clonidine.


Social relationships, stigma and adherence to antiretroviral therapy for HIV/AIDS.
Research on adherence to combination antiretroviral therapy has up to now focused largely upon problems of definition and measurement, and on the identification of barriers and supports. This paper examines the intersection between taking HAART and building a life with HIV/AIDS. Data consist of 214 qualitative interviews with 52 HIV-positive, active illegal drug users. A interpretive analysis drawing upon stigma and fear of disclosure as analytical constructs was applied to explain working tensions between efforts to develop social relationships on the one hand, and attempts to safeguard health through adherence on the other. The analysis specifies a mechanism through which stigma as a social process results in marginalization and exclusion. The hierarchical organization of multiple stigma is also noted. Loneliness and the desire for relatedness is intensified by drug use. Results suggest that persons with HIV/AIDS will not consistently subordinate other interests to prioritize adherence. Interventions aimed at supporting long-term adherence must address experienced conflicts between 'health' and 'life'.


The ovine model of neuronal ceroid lipofuscinosis (NCL): its contribution to understanding the pathogenesis of Batten disease.
Development of the ovine model of NCL has been pivotal to our present understanding of the ceroid lipofuscinoses. Analyses of isolated storage product have shown it to be composed of identifiable chemical species of which subunit c of mitochondrial ATP synthase is dominant (ca 50%). It is an extremely hydrophobic protein and failure to catabolise it may be associated with a propensity to form paracrystalline structures with lipids that cannot be degraded by the normal complement of lysosomal enzymes. However, the putative biochemical defect must be related to it and may reside within the mitochondria. Multiple copies of subunit c help form the transmembrane Fo complex which, with partially immobilised lipids, forms an Fo complex domain. This may need to be disassembled in an orderly fashion before proteolysis of subunit c can occur. It is postulated that the primary defect may involve disassembly of the Fo complex domain which may involve more than one step.


Kangen-karyu raises surface body temperature through oxidative stress modification.
Kangen-karyu, a prescription containing six herbs, has been shown to achieve its pharmacological effect through oxidative stress-dependent pathways in animal models. The aim of this study is to investigate the relationship between the antioxidative effect and pharmacological mechanisms of Kangen-karyu, specifically its body temperature elevating effect in humans. Healthy human volunteers, age 35 ± 15 years old, were enrolled in this study. Surface body temperature, serum nitrite, reactive oxygen species (ROS) scavenging activities, and inflammatory cytokines were investigated before and 120 min after Kangen-karyu oral intake. Kangen-karyu significantly increased the surface-body temperature of the entire body; this effect was more remarkable in the upper body and continued for more than 120 min. Accompanying this therapeutic effect, serum nitrite levels were increased 120 min after oral administration. Serum ROS scavenging activities were enhanced against singlet oxygen and were concomitantly decreased against the alkoxyl radical. Serum nitrite levels and superoxide scavenging activities were positively correlated, suggesting that Kangen-karyu affects the O2 (•-)-NO balance in vivo. Kangen-karyu had no effect on IL-6, TNF-α and adiponectin levels. These results indicate that the therapeutic effect of Kangen-karyu is achieved through NO- and ROS-dependent mechanisms. Further, this mechanism is not limited to ROS production, but includes ROS-ROS or ROS-NO interactions.


Exclusion of the oesophagus: is this a dangerous manoeuvre?
If oesophagectomy is contra-indicated or dangerous, oesophageal bypass can restore the ability to swallow. It is not known if excluding the bypassed oesophagus by closing both ends will lead to serious complications. In this study we report on 89 patients who underwent bypass surgery for benign and malignant strictures of the oesophagus. The thoracic oesophagus was completely excluded in 51 patients and in 30 cases the bypass procedure was combined with distal oesophageal drainage. Gastro-oesophageal continuity was preserved in eight patients undergoing an extra-oesophageal colon bypass. The operative mortality was similar in the three groups. Neck abscesses, probably due to leakage from the upper end of the bypassed oesophagus, occurred in 17 per cent of patients with oesophageal exclusion and in 9 per cent of the remainder. Changes occurring in the bypassed oesophagus of 38 patients were monitored with computed axial tomography. Segmental, mucus-filled dilatations ( mucocoeles ) of the oesophagus were identified in 20 patients. In 19 patients these mucocoeles remained small and asymptomatic. One patient with achalasia developed an oesophago-airway fistula two years after operation. Provided both ends of the oesophagus are securely closed, oesophageal exclusion is not a dangerous manoeuvre in patients undergoing bypass surgery for locally invasive tumours or corrosive injuries of the oesophagus.