Differential effects of NMDA receptor and dopamine receptor antagonists on cocaine toxicities.
Cocaine produces not only euphoric effects but also a wide range of detrimental effects, including seizures and lethality. The present study examined the involvement of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptors and the dopamine D1 and D2 receptors in seizure activity and lethality observed following single and repeated injections of cocaine in ddY mice. Repeated injections of 60 mg/kg cocaine resulted in the development of sensitization to the convulsant effects of cocaine during an initial 3 or 4 days, followed by the development of tolerance at day 5 and day 6. Repeated injections of 90 mg/kg cocaine augmented the lethal effect of cocaine progressively over the course of treatment. Treatment with 0.1-0.4 mg/kg of the noncompetitive NMDA receptor antagonist, MK-801, prevented the development of sensitization to cocaine-induced seizures in a dose-dependent manner, and attenuated partially the cocaine-induced lethality. In contrast, treatment with 10-50 mg/kg of the dopmaine D2 receptor antagonist, sulpiride, had no effects on the development of sensitization and tolerance to cocaine-induced seizures. On the other hand, treatment with 0.1-0.5 mg/kg of the dopamine D1 receptor antagonist, SCH 23390, not only prolonged the latency to 90 mg/kg cocaine-induced seizures but also delayed the development of sensitization to the convulsant effects of cocaine. The increased lethality observed following repeated injection of cocaine was unaffected by treatment with SCH 23390, but was severely aggravated by treatment with sulpiride.(ABSTRACT TRUNCATED AT 250 WORDS)


Modified deep iliac circumflex osteocutaneous flap for extremity reconstruction: anatomical study and clinical application.
The classic deep iliac circumflex osteocutaneous flap with iliac crest has been one of the most commonly used flaps for mandibular reconstruction since its advent. However, the unnecessary bulk of the 'obligatory muscle cuff' limited its widespread use. The authors describe in this article the use of a modified deep iliac circumflex osteocutaneous flap with reduced bulk and great mobility between the skin and the bone components. This study was divided into two parts: anatomical study and clinical application. In the anatomical study, 40 sides of adult cadaveric specimens perfused with red gelatin in the arteries were dissected with the anterior superior iliac spine and the inguinal ligament serving as the anatomical landmarks to observe the course and the branches of the deep circumflex artery, with its terminal part being given priority. Clinically, five patients received modified deep iliac circumflex osteocutaneous flaps for extremity reconstruction. The anatomical study showed that the terminal part of the deep circumflex iliac artery ended as a musculocutaneous perforator with a diameter of 1.0 ± 0.1 mm, which could be located 6.2 ± 1.2 cm posterior and 1.5 ± 0.6 cm lateral to the anterior superior iliac spine. As for clinical application, in four cases osteocutaneous flaps survived completely, while that in one case suffered partial loss of the skin component. The modified deep iliac circumflex osteocutaneous flap enjoys a great degree of mobility between the skin and the bone components; it has greater manoeuvrability compared to the conventional one for the reconstruction of complex three-dimensional defects. The donor site of the skin flap is confined to the lower abdominal region, facilitating direct closure.


Harms associated with gambling: abbreviated systematic review protocol.
According to the Gambling Commission, in 2018, almost half of the general population aged 16 and over had participated in gambling in the 4 weeks before being surveyed. Such surveys suggest that the proportion of people who are classed as 'problem' gamblers is relatively small; however, this may be related to the ways data are collected and gambling behaviour is classified. Concern about the harms associated with gambling is rising, and in response, Public Health England (PHE) has initiated this review to identify the harms associated with this activity. Harms to the gambler, their close associates and the wider society will all be included. Abbreviated systematic review processes will be employed. Ovid MEDLINE, Ovid Embase, Ovid Psycinfo, NICE Evidence and EBSCO SocIndex; a range of websites (for grey literature); and reference lists of included studies will be searched. Experts will be asked to identify other relevant literature. Literature published in years 2005-2019, published in English, from a country within the Organisation for Economic Development (OECD) and following an observational, qualitative or systematic review design will be included. AMSTAR2 (systematic reviews), the Newcastle-Ottawa Scale (observational studies) and the Critical Appraisal Skills Programme (CASP) qualitative checklist (qualitative studies) will be used to assess the risk of bias. A narrative synthesis will be used to summarise the results. The body of evidence will also be assessed according to the principles laid out in the CERQual approach. This protocol provides details of the framework that has been set up to guide this systematic review. The results of this review will provide an extensive assessment of the breadth and magnitude of harms associated with gambling. This will be one of the most comprehensive reviews of gambling-related harms undertaken to date. PROSPERO CRD42019154757.


An improved host-vector system for Candida maltosa using a gene isolated from its genome that complements the his5 mutation of Saccharomyces cerevisiae.
The host-vector system of an n-alkane-assimilating-yeast, Candida maltosa, which we previously constructed using an autonomously replicating sequence (ARS) region isolated from the genome of this yeast, utilizes C. maltosa J288 (leu2-) as a host. As this host had a serious growth defect on n-alkane, we developed an improved host-vector system using C. maltosa CH1 (his-) as host. The vectors were constructed with the Candida ARS region and a DNA fragment isolated from the genome of C. maltosa. Since this DNA fragment could complement histidine auxotrophy of both C. maltosa CH1 and S. cerevisiae (his5-), we termed the gene contained in this DNA fragment C-HIS5. The vectors were characterized in terms of transformation frequency and stability, and the nucleotide sequence of C-HIS5 was determined. The deduced amino acid sequence (389 residues) shared 51% homology with that of HIS5 of S. cerevisiae (384 residues; Nishiwaki et al. 1987).


Translocation t(14;18) and gain of chromosome 18/BCL2: effects on BCL2 expression and apoptosis in B-cell non-Hodgkin's lymphomas.
Gain of chromosome 18q and translocation t(14;18) are] frequently found in B-cell non-Hodgkin's lymphomas (B-NHL). Increased BCL2 transcription and BCL2 protein expression have been suggested to be the result of the gain. We utilized FISH, PCR and array CGH to study BCL2 and chromosome 18 copy number changes and rearrangements in 93 cases of B-NHL. BCL2 protein was expressed in >75% of the tumor cells in 92% of the cases by immunohistochemistry. Gain of BCL2 was associated with a 25% increase in BCL2 expression levels (immunoblotting), whereas t(14;18) resulted in a 55% increase in BCL2 levels compared to cases without BCL2 alterations. The tumor cell (spontaneous) apoptotic fractions were similar for the cases with different BCL2 genotypes. However, the normal cell apoptotic fractions were higher for the tumors with t(14;18) compared to the tumors without BCL2 alterations, while the tumors with gain of BCL2 only showed intermediate levels. Low-level gains of parts of chromosome 18 were found in 14 of the 38 B-NHL cases with t(14;18), with a consensus region 18pter-q21.33 that did not include the BCL2 gene. The 11 cases with 18q gain only showed a consensus region encompassing 18q21.2-18q21.32 and 18q21.33, which contain PMAIP1/MALT1 and BCL2, respectively.


Patellar instability following total knee replacement -- the dangers of constant design evolution.
Patellar instability following total knee replacement although infrequent can cause disabling symptoms. We report a case of symptomatic patellar instability caused by insertion of left femoral component into a right knee. We highlight that all members of the surgical and theatre team need to be familiar both with the implant equipment and of any recent design modifications, particularly if they have been used to using one system for a long time, in order to prevent surgical errors. In addition this possibility should be born in mind by surgeons looking for causes of post-operative patellar instability.


Spectral optical coherence tomography findings in adult-onset foveomacular vitelliform dystrophy.
Adult-onset foveomacular vitelliform dystrophy (AOFVD) is typically bilateral and symmetrical. We present the spectral optical coherence tomography (OCT) findings in two patients with unilateral AOFVD. Case 1 represents a 76-year-old man followed angiographically over the last 6 years for a macular lesion in his right eye. Visual acuity in the right eye has decreased from 1.0 to 0.6. In case 2, a 69-year-old man presented with blurred vision in his right eye. Visual acuity was 0.7 in the right eye and 1.0 in the left eye. In both patients, spectral OCT (Copernicus SOCT System) was performed. In case 1, fluorescein angiography showed a juxtafoveal hyperfluorescent lesion 2 / 3 of disc area in size, without late leakage. OCT showed a cystic oval lesion with thick walls, located between the retinal pigment epithelium (RPE) and photoreceptor layers. In case 2, OCT showed a hyperreflective round lesion also located between the RPE and photoreceptor layers, elevating the overlying inner retina. Spectral OCT enables enhanced visualization of the retinal layers and provides useful information regarding the diagnosis and the exact location of AOFVD.


[Study on how schizophrenic patients perceive treatment with injections in the deltoid muscle].
Despite the advantages of antipsychotic treatments via the injectable route of administration, there are still reservations regarding this type of therapy, notably among health professionals. A survey conducted with patients suffering from schizophrenic disorders revealed the positive opinion that they had of their treatment. Another survey showed that nearly half of the patients preferred an injectable form, and two thirds felt they were cared for better, because of the injectable treatment. The slow release form of risperidone allows a choice between two injection sites: the deltoid muscle or the gluteal muscle. A recent study showed the satisfaction of the health professionals towards this novel form. The survey presented here was aimed at collecting the opinion of patients regarding the possibility of choosing the injection site, and the changes it would make. The survey was carried out by the BVA Institute during the first half of 2011. The interviews with the schizophrenic patients, followed-up as out patients and treated with long lasting antipsychotics (n=281), were conducted face to face at the hospital by BVA interviewers specialised in the field of health, without the presence of any health professionals. A total of 32 centres participated in the survey; 38% of the interviews took place in the Paris area and 62% in various regions. Different dimensions were analysed. (1) The perception of injectable treatment was largely positive: among all the patients, 75% claimed they currently felt better once they had started the injectable treatment. (2) The choice of the injection site appeared important to a majority of patients (70% of the total sample; 79% of patients had experienced both sites of injection), 56% claimed that it was legitimate that they be given the choice and they felt that they were thus able to participate in their treatment (58%), their treatment was more acceptable (54%), and they found that their relationship with the doctor or nurse was enhanced (53%). (3) The preference regarding the injection site went to the deltoid muscle, among those who had experienced both sites. (4) The perception of the injection sites confirms this preference, the positive qualifications often being associated with the deltoid site, and the negative qualifications with the gluteal site. The survey presented here could contribute in convincing the health professionals to propose the choice to patients between the two injection sites in order to improve their compliance to treatment. Patients would therefore play a role in the choice of their treatment and hence become more involved in the follow-up.


Effect of adaptive opportunity on cognitive performance in warm environments.
This study investigates the hypothesis that thermal adaptive opportunities available to building occupants affect their cognitive performance and mental workload. The change rate of cerebral blood flow (Δtotal Hb) was measured by Near Infra-Red Spectroscopy (NIRS) and interpreted as the metric of mental workload in subjects while performing cognitive tasks (n-back tests) with, or without access to thermal adaptive opportunities such as regulable fan-induced air flow and clothing insulation adjustment. Participants underwent three experimental conditions: Condition 22 (operative temperature to = 22 °C without adaptive opportunities), Condition 28 (to = 28 °C without adaptive opportunities), and Condition 28w (to = 28 °C with adaptive opportunities. Under Condition 28w, thermal sensations were neutral, while thermal satisfaction and comfort levels were higher than those reported for Condition 28, and the same as those reported under Condition 22. The subjects' mean skin temperature under Condition 22 was the lowest at 32.1 °C, followed by Condition 28w at 33.6 °C, while the highest, 34.5 °C was recorded in Condition 28. No significant differences were observed in accuracy and reaction time of n-back tests between the three different environmental conditions. Under Condition 28w, mental fatigue levels and the left side Δ total Hb results were lowest out of all three conditions, although the differences failed to reach statistical significance. Availability of adaptive opportunities plays a role in expanding the range of thermal environmental conditions for optimal cognitive task performance in a moderately warm environment (to = 28 °C). This finding cannot be fully explained by the direct effect of adaptive behaviours on human heat balance and associated physiological responses, but the unexplained component may potentially be attributed to the psychological dimension of human adaptive response. These findings and their interpretation within an adaptive comfort framework are consistent with the extended-U hypothesis of cognitive performance.


Transient elastohydrodynamic lubrication analysis of metal-on-metal hip implant under simulated walking conditions.
The transient elastohydrodynamic lubrication (EHL) analysis was performed in this study for a typical metal-on-metal bearing employing a polyethylene backing underneath a metallic cup inlay under dynamic operating conditions of load and speed representative of normal walking. A ball-in-socket configuration was adopted to represent the articulation between the femoral head and the acetabular cup. The governing Reynolds and elasticity equations were solved simultaneously by using both finite difference and finite element methods. The predicted transient film thickness from the present study was compared with the estimation based on the quasi-static analysis. It was found that the polyethylene backing employed in the typical metal-on-metal hip bearing, combined with dynamic squeeze-film action, significantly improved the transient lubricant film thickness under cyclic walking and consequently a fluid film lubrication regime was possible for smooth bearing surfaces with an average roughness less than 0.005 microm.


Activation of the mitochondrial death pathway is commonly mediated by a preferential engagement of Bak.
Among the members of the Bcl-2 family, the multidomain proteins Bax and Bak are crucial for the activation of mitochondria. However, it is still unclear whether they act in a unique and distinct manner or whether they exhibit redundant functions. To systematically investigate their activation on a single-cell level, we established MCF-7 cell lines stably expressing GFP-fusion variants of these proteins. We found that MCF-7/GFP-Bak cells showed an increased sensitivity to apoptosis induction by staurosporine, actinomycin D, TRAIL and overexpression of Puma compared to GFP-Bax-expressing cells. Independently of the death stimulus used, oligomerization of endogenous and exogenous Bak was mostly detected prior to an activation of Bax, whereas cells displaying oligomerized Bax in the absence of Bak clusters were not observed. In addition, activation of Bax but not Bak was attenuated by a caspase inhibitor. Consistent with this, caspase-3-deficient MCF-7 cells displayed a significantly reduced activation of endogenous Bax than caspase-3-proficient MCF-7 cells. Thus, our data strongly suggest that diverse apoptotic stimuli preferentially engage the Bak pathway, whereas the triggering of Bax occurs, at least partially, downstream of mitochondrial caspase activation, most likely constituting a positive feedback loop for the amplification of the death signal.


Subcellular distribution of disaturated phosphatidylcholine in developing rabbit lung.
To determine the subcellular distribution of disaturated phosphatidylcholine (DSPC) in lung tissue during perinatal development, fetal rabbits at 24, 26, 28 and 31 (term) days gestation and newborns were studied. Following alveolar lavage, fractions enriched in nuclei-cellular debris, mitochondria, microsomes, surfactant (lamellar bodies) and cytosol were prepared from the residual tissue homogenate, and their DSPC content was determined. The DSPC content of the unfractionated residual lung tissue homogenate progressively and significantly increased during fetal development, rising from 9.09 +/- 0.91 to 17.45 +/- 2.88 mg/g dry lung between 24 days gestation, and term. Between 24 and 26 days gestation the overall increase in tissue DSPC was due to a two-fold increase in the mitochondrial, microsomal and cytosolic pools. Lamellar bodies were first isolable at 26 days gestation. The DSPC content of this fraction increased six-fold (from 0.10 +/- 0.02 to 0.67 +/- 0.15 mg/g dry lung) between 26 and 28 days gestation and a further seven-fold (to 4.63 +/- 1.06 mg/g dry lung) by term, accounting for the overall increase in the tissue homogenate value during this time period. By the first postnatal day, microsomal and cytosolic DSPC increased another two-fold, but no significant change occurred in the other subcellular fractions. Alveolar lavage DSPC progressively increased over the time period studied. While there was no change in the lamellar body DSPC/total PC ratio during fetal development, each of the mitochondrial, microsomal and cytosolic ratios decreased between days 26 and 28 of gestation and then increased at term.(ABSTRACT TRUNCATED AT 250 WORDS)


Phototoxicity of skin microorganisms tested with a new model.
A new standardized method for testing phototoxicity of chemicals against microorganisms is described. The inoculum size of the microorganism, application of test chemicals, prediffusion time, incubation time and incubation period are defined. Staphylococcus aureus, S. epidermidis, Candida albicans, and Pityrosporum orbiculare were studied. Both 8-methoxypsoralen and trimethylpsoralen were phototoxic against all microorganisms tested, while tetracycline and doxycycline were not phototoxic. C. albicans may be chosen for phototoxicity testing because it has been used earlier, it is easy to maintain in culture, it grows easily when tested, and its pathogenicity is low. The phototoxicity of S. aureus, S. epidermidis, Pseudomonas aeruginosa, Propionibacterium acnes, C. albicans, and P. orbiculare against each other were also investigated. Only P. orbiculare was inhibitory. It inhibited the growth of S. aureus, S. epidermidis, and Ps. aeruginosa - both in the dark and after irradiation. The growth inhibition was markedly enhanced after UVA irradiation, indicating phototoxicity. The phototoxic effect of P. orbiculare may play a role in the ecology of the human skin flora.


Pharmacokinetics of amoxicillin and flucloxacillin following the simultaneous intravenous administration of 4 g and 1 g, respectively.
The combination of amoxicillin and flucloxacillin not only widens the spectrum of pathogenic organisms covered by either of the substances alone; synergy has also been observed, particularly against beta-lactamase-producing organisms. For this reason, the possible interaction of these two penicillins regarding their pharmacokinetics was investigated with respect to therapeutic application. The parameters were calculated on the basis of an open two-compartment model. The highest serum levels of amoxicillin from 551 to 1074 mg/l when 4 g were administered alone, and from 403 to 1133 mg/l when administered together with 1 g flucloxacillin. Flucloxacillin concentrations ranged from 118 to 357 mg/l when administered alone, and from 151 to 226 mg/l in the presence of amoxicillin. Thus, there is no significant difference in the peak levels of either substance when given alone or in combination. The pharmacokinetic parameters of both substances basically do not depend on the presence of the other. A slight decrease was observed in the distribution rate of amoxicillin from the central to the peripheral compartment in the presence of flucloxacillin. Its relevance is questionable, however, since the effect was only minor.


Long coverage with drug-eluting stents is superior to spot coverage for long femoropopliteal artery disease: PARADE II study.
The efficacy of spot stenting using drug-eluting stents (DES) for the treatment of long femoropopliteal (FP) lesion is unknown. This study aimed to compare clinical outcomes of long full coverage vs. spot coverage with DES for long FP artery disease. This multicenter randomized trial compared long DES vs. spot DES for FP lesions longer than 150 mm. All lesions were treated with paclitaxel-eluting stents (Zilver PTX). The primary endpoint was primary patency at 12 months. The study was terminated early after an interim analysis. A total of 103 patients (55 in the long DES group; 48 in the spot DES group) were eligible for analysis. There were no significant differences in baseline and lesion characteristics between groups. Total stent length was longer in the long DES group than in the spot DES group (225.6 ± 67.2 vs. 131.3 ± 48.7 mm, p < 0.001). Technical success was achieved in all patients. There was a trend toward a higher primary patency rate at 12 months in the long DES group than in the spot DES group (87.5% vs. 67.5%, p = 0.120). The rate of survival free from target lesion revascularization was significantly higher in the long DES group than in the spot DES group (91.7% vs. 72.0%, p = 0.044). In multivariate Cox regression analysis, spot DES [hazard ratio (HR) 2.42, 95% confidence interval (CI) 1.14-5.12, p = 0.021] and postdilation (HR 0.27, 95% CI 0.09-0.79, p = 0.018) were identified as independent predictors for loss of patency at 12 months post-procedure. Long DES were more effective than spot DES for treating long FP lesions. Clinicaltrials.gov, identifier: NCT02701881.


A new intragastric delivery system for the treatment of Helicobacter pylori associated gastric ulcer: in vitro evaluation.
A new strategy is proposed for the triple drug treatment (tetracycline, metronidazole and bismuth salt) of Helicobacter pylori associated peptic ulcers. The design of the delivery system was based on the swellable asymmetric triple layer tablet approach, with floating feature in order to prolong the gastric retention time of the delivery system. Hydroxypropylmethylcellulose and poly(ethylene oxide) were the major rate-controlling polymeric excipients. Tetracycline and metronidazole were incorporated into the core layer of the triple-layer matrix for controlled delivery, while bismuth salt could be included in one of the outer layers for instant release. The concentration of tetracycline and metronidazole released over time was determined simultaneously on a gradient high-performance liquid chromatography system. Results demonstrated that sustained delivery of tetracycline and metronidazole over 6-8 h can be easily achieved while the tablet remained afloat. The floating aspect was envisaged to extend the gastric retention time of the designed system to maintain effective localized concentration of tetracycline and metronidazole. Additionally, the developed HPLC method for the concurrent determination of tetracycline and metronidazole was proved to be rapid and accurate. The developed delivery system has potential to increase the efficacy of the therapy and improve patient compliance.


Characterization and genome functional analysis of the DDT-degrading bacterium Ochrobactrum sp. DDT-2.
A strain of Ochrobactrum sp. DDT-2 that was capable of degrading DDT as the sole carbon and energy source was isolated and sequenced, and its biodegradation characteristics and metabolism mechanism were examined. The genome sequence of the isolate DDT-2 was composed of 4,630,303bp with a GC content of 55.99% and 4454 coding genes. The degradation rate of DDT by the isolate DDT-2 increased with the increasing substrate concentration (0.1-10mg/l) and temperature (20-40°C). The degradation half-life of DDT in the presence of the isolate DDT-2 at pH7.0 was obviously shorter than those at pH5.0 and 9.0. Potential DDT degradation genes were found in the isolate DDT-2 genome by a BLASTx search against a DDT degradation genes (DDGs) database. A common biodegradation pathway of DDT was proposed based on the combined analysis of genome annotation and mass spectrometry. DDT was initially dechlorinated to form DDD and DDE. Then, it was transformed into DDMU and DDA via dechlorination and carboxylation, and it may ultimately be mineralized to carbon dioxide. The results suggested that the isolate DDT-2 could be useful for the bioremediation of DDT and its metabolite residues.


Prenatal, birth and early life predictors of sedentary behavior in young people: a systematic review.
Our aim was to systematically summarize the evidence on whether prenatal, birth and early life factors up to 6 years of age predict sedentary behavior in young people (≤18 years). PRISMA guidelines were followed, and searches were conducted in PubMed, SPORTDiscus, EMBASE and Web of Science up to December 1, 2015. We included observational (non-intervention) and longitudinal studies, that reported data on the association between one or more of the potential predictors and objectively or subjectively measured sedentary behavior. Study quality was assessed using a formal checklist and data extraction was performed using standardized forms independently by two researchers. More than 18,000 articles were screened, and 16 studies, examining 10 different predictors, were included. Study quality was variable (0.36-0.95). Two studies suggest that heritability and BMI in children aged 2-6 years were significant predictors of sedentary behavior later in life, while four and seven studies suggest no evidence for an association between gestational age, birth weight and sedentary behavior respectively. There was insufficient evidence whether other prenatal, birth and early life factors act as predictors of later sedentary behavior in young people. The results suggest that heritability and early childhood BMI may predict sedentary behavior in young people. However, small number of studies included and methodological limitations, including subjective and poorly validated sedentary behavior assessment, limits the conclusions. The systematic review is registered in the International Prospective Register of Systematic Reviews, PROSPERO, 17.10.2014 ( CRD42014014156 ).


Structural characterization and in vitro antitumor activity of a novel polysaccharide isolated from the fruiting bodies of Pleurotus ostreatus.
A novel water-soluble polysaccharide (POPS-1) was obtained from the fruiting bodies of Pleurotus ostreatus by hot water extraction, ethanol precipitation, and fractionated by DEAE-cellulose ion exchange chromatography and sepharose CL-6B gel filtration chromatography using an ATKA explore 100 purifier. The structure characterization and antitumor activity of the POPS-1 were evaluated in this paper. According to GC analysis, HPGPC, FT-IR, partial acid hydrolysis, periodate oxidation and Smith degradation, methylation and GC-MS analysis, the results indicate POPS-1 (M(w)=31 kDa) was composed of Man; Gal; Glc with a molar ratio of 1:2.1:7.9, it had a backbone of beta-(1-->3)-linked glucose residues, which occasionally branches at O-6. The branches were composed of (1-->3)-linked Glc, (1-->4)-linked Gal, (1-->4)-linked Man, and terminated with Glc and Gal residues. Cytotoxicity assay showed POPS-1 presented significantly higher antitumor activity against Hela tumor cell in vitro, in a dose-dependent manner, and exhibited significantly lower cytotoxicity to human embryo kidney 293T cells than Hela tumor cells compared with 5-Fu. The results suggest POPS-1 may be considered as a potential candidate for developing a novel low toxicity antitumor agent.


Hepatitis B transmission within families: potential importance of saliva as a vehicle of spread.
We report a family, extensively affected by hepatitis B virus (HBV), in whom sexual or vertical transmission is unlikely to account entirely for the intra-family clustering of the virus. HBV-DNA was detected in saliva in one family member and we suggest that spread by salivary transmission could account for at least some of the intra-family infection and could contribute to the "inapparent parenteral" spread of hepatitis B.


Successful apexification with resolution of the periapical lesion using mineral trioxide aggregate and demineralized freeze-dried bone allograft.
Immature teeth with necrotic pulp and large periapical lesion are difficult to treat via conventional endodontic therapy. The role of materials such as calcium hydroxide and mineral trioxide aggregate in apexification is indispensable. This case report presents the successful healing and apexification with combined use of white mineral trioxide aggregate and demineralized freeze-dried bone allograft.


Age-related decline of acetylcholine release evoked by depolarizing stimulation.
Release of endogenous acetylcholine (ACh) from the dorsal hippocampus in response to depolarizing stimulation with high-K+ infusion was examined in young and aged rats using the method of in vivo dialysis. ACh content in the dialysate was determined by high-performance liquid chromatography-electrochemical detection (HPCC-ECD). During the high-K+ stimulation, the concentration of ACh in the dialysate only slightly increased in aged rats in contrast with young rats where the ACh content during stimulation increased about 2-fold of the basal level. These results showed that ACh release evoked by depolarizing stimulation declined through aging in the hippocampus.


Progesterone has rapid and membrane effects in the facilitation of female mouse sexual behavior.
Ovariectomized (ovx) mice require both estradiol (E2) and progesterone (P) administration to reinstate feminine sexual behavior (lordosis). The importance of P's actions at E2-induced intracellular progestin receptors (PRs) to facilitate lordosis was investigated in PR knockout (PRKO) mice, PRKO's wild type littermates (C57X129), and wild type C57BL/6J (C57) mice. Subjects were ovx, E2-primed (0.5 microg) and tested following intravenous (i. v.) and intercereberal P. Intravenous P (200 microg) significantly increased lordosis of all mice within 10 min of P, but vehicle infusion did not (Experiment 1). Intravenous P significantly increased the amount and duration and reduced the latency of lordosis, over that seen with vehicle infusion, in PRKO and wild type mice. Whole brain concentrations of P and its 5alpha-reduced metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), which has low affinity for intracellular PRs, were also increased following P compared to vehicle infusion. Progesterone, but not vehicle infusions, significantly increased the number of PR-immunoreactive (PR-IR) cells in the ventromedial hypothalamus (VMH) of C57 and C57X129 mice and increased number of 3alpha, 5alpha-THP-immunoreactive (3alpha,5alpha-THP-IR) cells in the ventral tegmental area (VTA) of all mice. In Experiment 2, P conjugated to bovine serum albumin (P:BSA) increased lordosis when applied bilaterally to both the VMH and VTA of E2-primed mice more than BSA implants. Progesterone implants increased the number of PR-IR cells in the VMH of C57 and C57X129 mice and the number of 3alpha,5alpha-THP-IR cells in the VTA of all mice. The rapid facilitation of lordosis with i.v. P infusion and increases in lordosis when P's effects are relegated to the membrane in the VMH and VTA of PRKO and wild type mice suggest that P may facilitate lordosis through actions at substrates other than intracellular PRs. The present findings suggest a role of 3alpha,5alpha-THP.


Perturbations of membrane structure by optical probes: II. Differential scanning calorimetry of dipalmitoyllecithin and its analogs interacting with Merocyanine 540.
Differential scanning calorimetry of multilamellar liposomes, interacting with the optical probe Merocyanine 540, yields quantitative information about perturbances of the bilayer structure induced by this dye. At low dye: lipid ratios, the dye perturbs primarily its own microenvironment, which is laterally separated from the unmodified lipid domain and exhibits modified thermotropic properties. A further increase in the dye concentration results in a perturbance of the whole lipid bilayer. The degree of perturbance is sensitive to structural modifications in the head-group region of the lipids. It is concluded that Merocyanine 540 reports in every case, even at infinite dilution, on localized events originating from a perturbed microenvironment.


Genetic mapping of the wheat leaf rust resistance gene Lr19 and development of translocation lines to break its linkage with yellow pigment.
The leaf rust resistance gene Lr19, which is present on the long arm of chromosome 7E1 in Thinopyrum ponticum, was mapped within a 0.3-cM genetic interval, and translocation lines were developed to break its linkage with yellow pigmentation The leaf rust resistance locus Lr19, which was transferred to wheat (Triticum aestivum) from its relative Thinopyrum ponticum in 1966, still confers broad resistance to most known races of the leaf rust pathogen Puccinia triticina (Pt) worldwide. However, this gene has not previously been fine-mapped, and its tight linkage with a gene causing yellow pigmentation has limited its application in bread wheat breeding. In this study, we genetically mapped Lr19 using a bi-parental population from a cross of two wheat-Th. ponticum substitution lines, the Lr19-carrying line 7E1(7D) and the leaf rust-susceptible line 7E2(7D). Genetic analysis of the F2 population and the F2:3 families showed that Lr19 was a single dominant gene. Genetic markers allowed the gene to be mapped within a 0.3-cM interval on the long arm of Th. ponticum chromosome 7E1, flanked by markers XsdauK3734 and XsdauK2839. To reduce the size of the Th. ponticum chromosome segment carrying Lr19, the Chinese Spring Ph1b mutant was employed to promote recombination between the homoeologous chromosomes of the wheat chromosome 7D and the Th. ponticum chromosome 7E1. Two translocation lines with short Th. ponticum chromosome fragments carrying Lr19 were identified using the genetic markers closely linked to Lr19. Both translocation lines were resistant to 16 Pt races collected throughout China. Importantly, the linkage between Lr19 and yellow pigment content was broken in one of the lines. Thus, the Lr19 linked markers and translocation lines developed in this study are valuable resources in marker-assisted selection as part of common wheat breeding programs.


Laparoscopic reoperative antireflux surgery.
Antireflux operations for gastroesophageal reflux disease whether performed open or laparoscopically can fail and may require reoperation to control new, recurrent symptoms or operation-related complications. We report our experience with the laparoscopic reoperation for failed antireflux procedures. Between 1995 and 2000, 37 patients underwent laparoscopic reoperative antireflux procedures. The mean age and weight were 52 years and 181.5 pounds. The main presenting symptoms were heartburn (n = 18), respiratory reflux (n = 4), chest pain (n = 3), regurgitation (n = 1), and dysphagia (n = 10). The mean duration between the first operation and recurrence of symptoms was 18 months, and the duration between the two procedures was 25 months. The operation was completed laparoscopically in 32 patients (86.5%): Nissen fundoplication (n = 27) and Toupet fundoplication (n = 9). Intraoperative and postoperative complications occurred in 6 and 14 patients, respectively. Fundoplication disruption was the most common cause of primary surgery failure. The mean hospital stay was 4 days. At a mean follow-up of 26.5 months, results were excellent to good (65%), fair (21.5%), and poor (13.5%). Laparoscopic reoperative antireflux procedures are technically feasible with acceptable preliminary results.


Correction to: Biosynthesis of medicinally important plant metabolites by unusual type III polyketide synthases.
The article Biosynthesis of medicinally important plant metabolites by unusual.


Ecophysiological studies of Sonoran Desert plants : I. Diurnal photosynthesis patterns of Ambrosia deltoidea and Olneya tesota.
The gas exchange of two Sonoran Desert plants was measured near optimum soil water conditions occurring in the summer and winter. Photosynthesis and stomatal conductance rates of a drought-deciduous shrub, Ambrosia deltoidea, and an evergreen non-riparian tree, Olneya tesota, are mainly affected by plant water potential. During such periods the diurnal gas exchange patterns are characterized by maximum rates of photosynthesis and stomatal conductance occurring early in the day, which decrease progressively thereafter. The effect of plant water potential on gas exchange is both direct and indirect. Decreasing plant water potential indirectly affects 14CO2 assimilation by closure of stomata, and the effect is similar in both species. However, the direct effects of decreasing plant water potential are dissimilar in the two species. Plants of the shrub species have a higher potential maximum photosynthesis, but are more sensitive to plant water stress than are plants of the tree species. Both species respond to favorable growth conditions in the summer and winter, and have the potential for rapid carbon input into the Sonoran Desert ecosystem.


Combined education and skin antisepsis intervention for persistently high blood-culture contamination rates in neonatal intensive care.
Contaminated blood cultures represent challenges regarding diagnosis, duration of hospitalization, antimicrobial use, pharmacy and laboratory costs. Facing problematic neonatal blood culture contamination (3.8%), we instigated a successful intervention combining skin antisepsis using sterile applicators with 2% chlorhexidine gluconate in 70% isopropanol prior to phlebotomy (replacing 70% isopropanol) and staff education. In the six months prior to intervention, 364 neonatal peripheral blood samples were collected. Fourteen (3.8%) were contaminated. In the post-intervention six months, 314 samples were collected. Three (0.96%) were contaminated, representing significant improvement (Fisher's exact test: P = 0.0259). No dermatological sequelae were observed. The improvement has been sustained.


The effectiveness of video feedback in the acquisition of orthopedic technical skills.
The addition of video feedback to bench model training offers residents the opportunity to see themselves perform a surgical task. Videotaped feedback therefore promotes self-evaluation, a critical learning skill, and also has the potential to influence how a resident executes a skill once they have had the opportunity to see themselves perform the task. Twenty-nine surgical residents were video recorded while performing three technical skills. They then were randomly assigned to receive either no feedback, video feedback alone, or video feedback with the help of an expert, an orthopedic surgeon. The surgical task was then repeated. Orthopedic surgeons evaluated the videotapes using the global rating scale and technical checklist form. One-way between-subject analysis of variance comparing the pretest and post-test difference scores on three different measures for each of the three tasks revealed no statistically significant differences. After controlling for rater variance, the global rating scores across the three surgical tasks did not reveal any statistically significant differences. This study failed to demonstrate an improvement in technical skills based on utilization of video feedback.


Risk profiles of prostate cancers identified from UK primary care using national referral guidelines.
Prostate cancer in the United Kingdom is mainly diagnosed from primary care referrals based on national guidelines published by the Department of Health. Here we investigated the characteristics of cancers detected through the use of these guidelines. A prospective two-centre study was established to assess men referred from the primary care based on the UK national guidelines. The overall cancer detection rate was 43% (169 out of 397) with 15% (26 out of 169) of all cancers metastatic at presentation. Amongst 50-69-year-old men these rates were 34% (68 out of 200) and 15% (10 out of 68). Only 21% (25 out of 123) of men with local cancers had low-risk disease. In comparison to a historical cohort from 2001 (n=137) we found no overall differences in rates of metastatic disease, locally advanced tumours, or risk categories. Amongst 50-69-year-old men with local disease, however, we observed an increase in detection of low-risk cancers in a contemporary cohort (P=0.04). This was primarily because of the increased detection of low-stage organ-confined tumours in this group (P=0.02). Use of the UK prostate cancer guidelines detects a high proportion of clinically significant cancers. Use of the guidelines does not seem to have led to an overall change in the clinical characteristics of presenting cancers. There may, however, be a specific benefit in detecting more low-risk disease in younger men.


Intracardiac thrombus in Behçet's disease: two case reports.
Intracardiac thrombus in Behçet's disease is an extremely rare manifestation. We report two such cases. A 20-year-old man presented with dyspnoea, cough and haemoptysis. Right heart thrombus associated with pulmonary artery aneurysm and thromboembolism was identified by helical CT and transoesophageal echocardiography. The second case was a 29-year-old male admitted for fever and chest pain. A diagnosis of right atrial thrombosis associated with pulmonary embolism and hyperhomocysteinemia was made. Due to the absence of haemodynamic compromise, medical management consisting of immunosupressive and anticoagulation therapy was adopted which resulted in complete dissolution of the thrombus with dramatic clinical improvement in both cases of clinical status. intracardiac thrombus is a rare complication of Behçet's disease. As shown in our patients, medical treatment should be considered as the first line.


13C- and 15N-labeling of amyloid-β and inhibitory peptides to study their interaction via nanoscale infrared spectroscopy.
Interactions between molecules are fundamental in biology. They occur also between amyloidogenic peptides or proteins that are associated with different amyloid diseases, which makes it important to study the mutual influence of two polypeptides on each other's properties in mixed samples. However, addressing this research question with imaging techniques faces the challenge to distinguish different polypeptides without adding artificial probes for detection. Here, we show that nanoscale infrared spectroscopy in combination with 13C, 15N-labeling solves this problem. We studied aggregated amyloid-β peptide (Aβ) and its interaction with an inhibitory peptide (NCAM1-PrP) using scattering-type scanning near-field optical microscopy. Although having similar secondary structure, labeled and unlabeled peptides could be distinguished by comparing optical phase images taken at wavenumbers characteristic for either the labeled or the unlabeled peptide. NCAM1-PrP seems to be able to associate with or to dissolve existing Aβ fibrils because pure Aβ fibrils were not detected after mixing.


Design and SAR assessment of three compact 5G antenna arrays.
In this paper three different multi stub antenna arrays at 27-29.5 GHz are designed. The proposed antenna arrays consist of eight single elements. The structure of feeding parts is the same but the radiation elements are different. The feeding network for array is an eight way Wilkinson power divider (WPD). To guarantee the simulation results, one of the proposed structures is fabricated and measured (namely the characteristics of S11, E-, and H-plane patterns) which shows acceptable consistency with measurement results. The simulation results by CST and HFSS show reasonable agreement for reflection coefficient and radiation patterns in the E- and H- planes. The overall size of the proposed antenna in maximum case is 29.5 mm × 52 mm × 0.38 mm (2.8 [Formula: see text]× 4.86[Formula: see text] × 0.036[Formula: see text]). Moreover, for Specific Absorption Rate (SAR) estimation, a three-layer spherical human head model (skin, skull, and the brain) is placed next to the arrays as the exposure source. The simulation results show that the performance of proposed antennas as low-SAR sources makes them ideal candidates for the safe usage and lack of impact of millimeter waves (mmW) on the human health. In all three cases of SAR simulations the value of SAR1g and SAR10g are below the standard limitations.


Anticipatory changes of soleus H-reflex amplitude during execution process for heel raise from standing position.
Soleus (SOL) H-reflex amplitude changes before the EMG onset of that muscle were compared between simple plantar flexion (SPF) and heel raise from standing position (STM). Results indicated that (1) the SOL H-reflex amplitude decreased during the STM but not the SPF, (2) in the STM, anticipatory EMG activity in the antagonist tibialis anterior (TA) appeared before the EMG onset of the agonist (SOL) and the onset corresponded to the initiation of the decreasing SOL H-reflex, and (3) EMG reaction time of the SOL in the STM was significantly longer than in the SPF. These results suggest that the decreasing SOL H-reflex amplitude is caused by the reciprocal inhibition originating from the postural synergy, the TA. The functional significance of the decreased SOL H-reflex amplitude might lead to a delay in the activation of focal musculature.


GSM2, a transaldolase, contributes to reactive oxygen species homeostasis in Arabidopsis.
Plants are exposed to various environmental cues that lead to reactive oxygen species (ROS) accumulation. ROS production and detoxification are tightly regulated to maintain balance. Although studies of glucose (Glc) are always accompanied by ROS in animals, the role of Glc in respect of ROS in plants is unclear. We isolated gsm2 (Glc-hypersensitive mutant 2), a mutant with a notably chlorotic-cotyledon phenotype. The chloroplast-localized GSM2 was characterized as a transaldolase in the pentose phosphate pathway. With 3% Glc treatment, fewer or no thylakoids were observed in gsm2 cotyledon chloroplasts than in wild-type cotyledon chloroplasts, suggesting that GSM2 is required for chloroplast protection under stress. gsm2 also showed evaluated accumulation of ROS with 3% Glc treatment and was more sensitive to exogenous H2O2 than the wild type. Gene expression analysis of the antioxidant enzymes in gsm2 revealed that chloroplast damage to gsm2 cotyledons results from the accumulation of excessive ROS in response to Glc. Moreover, the addition of diphenyleneiodonium chloride or phenylalanine can rescue Glc-induced chlorosis in gsm2 cotyledons. This work suggests that GSM2 functions to maintain ROS balance in response to Glc during early seedling growth and sheds light on the relationship between Glc, the pentose phosphate pathway and ROS.


Isolation and Characterization of Biosurfactant-Producing Soil Fungus Penicillium sp.
In this study, a fungal species was isolated from rhizospheric soil and identified as Penicillium sp. by ITS sequencing. The Penicillium sp. has been screened for the biosurfactant production, viz., haemolytic activity, oil spreading assay and emulsification index. The biosurfactant from cell-free supernatant was extracted using acid precipitation followed by solvent-solvent extraction. The physiochemical properties of the extracted biosurfactant were analysed using FTIR; the major peaks that show at 1720 cm-1, 1531 cm-1, 1419 cm-1, 1251 cm-1 and 1010 cm-1 correspond to aliphatic chains, sugars and ester carbonyl groups. The fatty acids present in the extracted biosurfactant were analysed using GCMS, in which a molecular mass of 256 and 284 m/z showed the presence of n-hexadecenoic acid and octadecanoic acid respectively which indicate the presence of rhamnolipid, which is a major biosurfactant. The biosurfactant extracted from Penicllium sp. demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus. In future perspectives, the biosurfactant extracted from the isolated species holds great potential as a broad-spectrum antibacterial agent and could be utilized in various healthcare applications.


The elderly patient receiving radiation therapy: treatment sequelae and nursing care.
Preparing the elderly patient for radiation therapy requires knowledge of the major cancers, the role of radiation treatment, sequelae of treatment, and the age-associated factors that exacerbate treatment reactions. Elderly patients often require long treatment courses. Encouragement to express feelings and report symptoms may be necessary in this patient population. Instructions should be written and repeated, especially for patients with memory loss. The nurse caring for the elderly patient receiving radiation must help the patient to anticipate side effects and manage sequelae of treatment. The patient who knows what to expect is better able to tolerate therapy and to maintain an optimal quality of life during treatment.


New Flavones, a 2-(2-Phenylethyl)-4H-chromen-4-one Derivative, and Anti-Inflammatory Constituents from the Stem Barks of Aquilaria sinensis.
In the current study, two new flavones, 4'-O-geranyltricin (1) and 3'-O-geranylpolloin (2), and a new 2-(2-phenylethyl)-4H-chromen-4-one derivative, 7-hydroxyl-6-methoxy-2-(2-phenylethyl)chromone (3), have been isolated from the stem barks of A. sinensis, together with 21 known compounds 4-24. The structures of new compounds 1-3 were determined through spectroscopic and MS analyses. Compounds 2, 3, 5, 6, and 8-10 exhibited inhibition (IC50≤12.51 μM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 3, 6, 8, 10, and 19 inhibited fMLP/CB-induced elastase release with IC50 values≤15.25 μM. This investigation reveals bioactive isolates (especially 2, 3, 5, 6, 8, 9, 10, and 19) could be further developed as potential candidates for the treatment or prevention of various inflammatory diseases.


31P-nuclear magnetic resonance analysis of the intracellular pH in the slime mold Dictyostelium discoideum.
Amoebae of the slime mold D. discoideum were studied by phosphorus nuclear magnetic resonance. Under aerobic conditions, major intracellular phosphate compounds included phosphomonoesters, inorganic phosphate (Pi), ADP and ATP. Nucleotides were essentially as magnesium complexes. Two intracellular Pi resonances were clearly resolved and the corresponding pHs determined by the chemical shifts characteristics were 7.7 and 6.7. These intracellular pHs were strictly constant over an extracellular pH range between 5.0 and 7.5. The two cellular compartments defined by the Pi resonances were assigned to mitochondria (pH 7.7) and cytosol (pH 6.7) on the basis of their response to anaerobiosis or to carbonylcyanide-m-chloro phenylhydrazone (CCCP), an uncoupler of oxidative phosphorylation, which equilibrate the two intracellular pHs.


Exogenous and endogenous therapeutic effects of combination Sodium Ferulate and bone marrow stromal cells (BMSCs) treatment enhance neurogenesis after rat focal cerebral ischemia.
Combining bone marrow stromal cells (BMSCs) with pharmacological therapy is an attractive approach for neurological function recovery of stroke. Our previous reports demonstrated that Sodium Ferulate (SF) combined with BMSCs administration could facilitate BMSCs migration into the ischemic brain by up-regulation of stromal cell-derived factor-1 alpha (SDF-1α)/chemokine (CXC motif) receptor-4 axis after stroke. To further investigate whether combination treatment could enhance neurogenesis through exogenous and endogenous therapeutic effects, we established rat permanent middle cerebral artery occlusion (pMCAo) model and measured ischemic infarct size by magnetic resonance imaging (MRI) scanning in the present study. The results showed that combination treatment could dramatically reduce ischemic infarction size which may be attributed to the effects on decreasing brain edema and enhancing cerebral tissue perfusion at 3 days after stroke. Immunofluorescence staining results indicated that combination treatment could not only promote expression of Glucose transporter 1(Glut1) and Neuron-specific class III beta-tubulin (Tuj1) in the periinfarct area, but also improve BMSCs expression of Glut1, GFAP and Tuj1. Moreover, it showed combination treatment could enhance the endogenous expression of Tuj-1 in ischemic boundary zone. These results perhaps associated with combination treatment up-regulating bone morphogenetic proteins (BMP)2/4 expressions and down-regulating Notch-1, Hes1 and Hes5 expressions as detected by Western Blot analysis. Our study firstly demonstrated in vivo that combination treatment could facilitate exogenous BMSCs differentiation into neural-and astrocytic-like cells, as well as enhance repair capacity of brain parenchymal cells by promoting glucose metabolism and endogenous neurogenesis after stroke. These results illustrate that administration of SF and BMSCs is a potential pathway of cell-based pharmacological treatment towards ischemic stroke.


Preneoplastic Low-Risk Mammary Ductal Lesions (Atypical Ductal Hyperplasia and Ductal Carcinoma In Situ Spectrum): Current Status and Future Directions.
Intraepithelial mammary ductal neoplasia is a spectrum of disease that varies from atypical ductal hyperplasia (ADH), low-grade (LG), intermediate-grade (IG), to high-grade (HG) ductal carcinoma in situ (DCIS). While ADH has the lowest prognostic significance, HG-DCIS carries the highest risk. Due to widely used screening mammography, the number of intraepithelial mammary ductal neoplastic lesions has increased. The consequence of this practice is the increase in the number of patients who are overdiagnosed and, therefore, overtreated. The active surveillance (AS) trials are initiated to separate lesions that require active treatment from those that can be safely monitored and only be treated when they develop a change in the clinical/radiologic characteristics. At the same time, the natural history of these lesions can be evaluated. This review aims to evaluate ADH/DCIS as a spectrum of intraductal neoplastic disease (risk and histomorphology); examine the controversies of distinguishing ADH vs. DCIS and the grading of DCIS; review the upgrading for both ADH and DCIS with emphasis on the variation of methods of detection and the definitions of upgrading; and evaluate the impact of all these variables on the AS trials.


Complicated cholesteatomas: CT findings in inner ear complications of middle ear cholesteatomas.
Patients with facial palsy and middle ear disease, which may be chronic but clinically occult, may have a cholesteatoma with extension medially along the facial canal. In two patients, axial computed tomographic (CT) scans demonstrated involvement of the medial petrous bone. Patients with vertigo and chronic middle ear disease may have a cholesteatoma with a "fistula" between the middle and inner ears. Although the fistula usually involves the lateral semicircular canal, the cholesteatoma may pass through the oval window. In two patients, coronal CT scans showed extension to the oval window in one and through it in the other.


Prognostic models for upper urinary tract urothelial carcinoma patients after radical nephroureterectomy based on a novel systemic immune-inflammation score with machine learning.
This study aimed to evaluate the clinical significance of a novel systemic immune-inflammation score (SIIS) to predict oncological outcomes in upper urinary tract urothelial carcinoma(UTUC) after radical nephroureterectomy(RNU). The clinical data of 483 patients with nonmetastatic UTUC underwent surgery in our center were analyzed. Five inflammation-related biomarkers were screened in the Lasso-Cox model and then aggregated to generate the SIIS based on the regression coefficients. Overall survival (OS) was assessed using Kaplan-Meier analyses. The Cox proportional hazards regression and random survival forest model were adopted to build the prognostic model. Then we established an effective nomogram for UTUC after RNU based on SIIS. The discrimination and calibration of the nomogram were evaluated using the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration curves. Decision curve analysis (DCA) was used to assess the net benefits of the nomogram at different threshold probabilities. According to the median value SIIS computed by the lasso Cox model, the high-risk group had worse OS (p<0.0001) than low risk-group. Variables with a minimum depth greater than the depth threshold or negative variable importance were excluded, and the remaining six variables were included in the model. The area under the ROC curve (AUROC) of the Cox and random survival forest models were 0.801 and 0.872 for OS at five years, respectively. Multivariate Cox analysis showed that elevated SIIS was significantly associated with poorer OS (p<0.001). In terms of predicting overall survival, a nomogram that considered the SIIS and clinical prognostic factors performed better than the AJCC staging. The pretreatment levels of SIIS were an independent predictor of prognosis in upper urinary tract urothelial carcinoma after RNU. Therefore, incorporating SIIS into currently available clinical parameters helps predict the long-term survival of UTUC.


Antibody-dependent cell-mediated cytotoxicity (ADCC) in Aujeszky's disease.
Antibody-dependent cell-mediated cytotoxicity (ADCC) was studied using as targets 51Cr-labelled Vero cells infected with the Bartha strain of Aujeszky's disease virus (ADV). Using hyperimmune anti-ADV serum to sensitize the targets, porcine leukocytes from dextran-sedimented blood were found to be efficient effector cells yielding maximal 51Cr release by 16 hours. Whilst complement-dependent cytotoxic antibody could be demonstrated no enhancement of ADCC by complement was found. The sera of pigs vaccinated i.m. with Bartha virus were titrated in ADCC using leukocytes as effector cells and the results compared with those obtained by virus neutralization. ADCC proved to be a much more sensitive technique and might, therefore, provide the basis for a reliable diagnostic test. Partially purified lymphocytes and polymorphonuclear leukocytes from blood and peritoneal exudates, and macrophages from exudates were found to mediate ADCC with hyperimmune serum, but differences were observed in the efficiency and timing of their cytotoxic effects.


Contacts of pore tubules and sensory dendrites in antennal chemosensilla of a silkmoth: demonstration of a possible pathway for olfactory molecules.
Antennal olfactory hairs of Antheraea polyphemus were investigated by means of transmission electron microscopy. Adequate preservation of dendrites and extracellular pore tubules is obtained by mechanical opening of the hair lumen and subsequent chemical fixation. The dendritic membrane has a cell coat. The dendrites contain microfilamentous structures in addition to their cytoplasmatic microtubules. The extracellular pore tubules traverse the hair cuticle and reach into the hair lumen for maximally 350 nm. Their diameter varies between 20 and 40 nm, depending on the preparation method. They consist of an electron-dense wall and an electron-lucent core. The wall has a helical substructure and is covered with a fuzzy coat. Contacts of pore tubules and dendritic membranes occur wherever dendrites are near the inner surface of the hair cuticle. Some of the pore tubules terminate approximately at right angles on the dendritic membrane, others lie against the membrane. The contact seems to be made via the surface coats of the tubules and the membrane. The structure of pore tubules which had been negatively stained with uranyl acetate is similar to the conventionally thin-sectioned material. The observations provide support for earlier assumptions that pore tubules are the pathways by which odor molecules reach the dendritic membrane.


GATA3 immunohistochemical expression in salivary gland neoplasms.
GATA3 is a zinc finger transcription factor that regulates the normal development of many tissues and cell types. Recent studies have shown that immunohistochemical nuclear staining for GATA3 among tumors is highly restricted to carcinomas of breast and urothelial origin; however salivary gland tumors have not been tested. Given that breast and salivary gland tissues are very similar with respect to embryologic development and structure, we performed GATA3 staining on a spectrum of salivary gland neoplasms. GATA3 immunohistochemistry was performed on a diverse collection of 180 benign and malignant salivary gland neoplasms including 10 acinic cell carcinomas, 2 adenocarcinomas not otherwise specified, 41 adenoid cystic carcinomas, 2 epithelial-myoepithelial carcinomas, 1 low grade cribriform cystadenocarcinoma, 15 mammary analogue secretory carcinomas, 7 metastatic squamous cell carcinomas, 27 mucoepidermoid carcinomas, 2 oncocytic carcinomas, 5 oncocytomas, 34 pleomorphic adenomas, 4 polymorphous low grade adenocarcinomas, 25 salivary duct carcinomas, and 5 Warthin tumors. Staining for GATA3 was observed in 92/180 (51 %) of salivary gland tumors. GATA3 staining was observed in most of the tumor types, but diffuse immunolabeling was consistently seen in salivary duct carcinoma (25 of 25) and mammary analogue secretory carcinoma (15 of 15)-the two tumor types that most closely resemble breast neoplasia. Background benign salivary gland tissue was also usually weakly positive in both acini and ducts. GATA3 immunostaining is not restricted to tumors of breast and urothelial origin. Rather, it is expressed across many different types of salivary gland neoplasms. As a result, salivary gland origin should be considered in the differential diagnosis of a GATA3-positive carcinoma, particularly in the head and neck. Although GATA3 immunohistochemistry is not helpful in resolving the differential diagnosis between a primary salivary gland neoplasm and metastatic breast cancer, it may have some utility in subtyping salivary gland tumors, particularly salivary duct carcinoma and mammary analogue secretory carcinoma.


Exendin-4 inhibits small intestinal glucose sensing and absorption through repression of T1R2/T1R3 sweet taste receptor signalling in streptozotocin diabetic mice.
The small intestine, which is the area where sugars are absorbed, should be considered in the approaches developed for the treatment of diabetes. However, studies on small intestine damage in diabetic individuals, and the effects of current treatments on the small intestine are very limited. This is the first study to investigate the effects of exendin-4, a GLP-1 receptor agonist, on small intestine injury in diabetic mice. BALB/c male mice were divided into 4 groups for this study. The first group was given citrate buffer, the second group was given exendin-4, the third group was given streptozotocin (STZ), and the fourth group was given both exendin-4, and STZ. As the results, we determined a decrease in the edema and deterioration in the integrity of the villi, disruption in continuity of the brush border, fibrosis and enterocyte apoptosis, while the TNFα level and crypt cell proliferation were increased in the small intestinal tissue of exendin-4 treated STZ diabetic mice. Furthermore, the levels of duodenal tissue glucose, SGLT1, and GLUT2 were decreased, whereas there was an increase in GIP level in diabetic mice administered with exendin-4. Moreover, we determined that the sweet taste receptors T1R2/T1R3, downstream molecules PLCβ2, α-gustducin and associated secondary messengers IP3, cAMP, which were increased in the duodenal tissue of STZ-diabetic mice, decreased with exendin-4 administration. These findings were evaluated as that exendin-4 reduces glucose absorption by suppressing the T1R2/T1R3 sweet taste signal perception pathway in duodenum of STZ diabetic mice.


Common combinations of medications used among oldest-old women: a population-based study over 15 years.
Older people use many medications, but combinations of medications used among the oldest old (≥ 80 years) are not commonly reported. This study aimed to determine common combinations of medications used among women aged 77-96 years and to describe characteristics associated with these combinations. A cohort study of older women enroled in the Australian Longitudinal Study on Women's Health over a 15-year period was used to determine combinations of medications using latent class analysis. Multinomial logistic regression was used to determine characteristics associated with these combinations. The highest medication users during the study were for the cardiovascular (2003: 80.28%; 2017: 85.63%) and nervous (2003: 66.03%; 2017: 75.41%) systems. A 3-class latent model described medication use combinations: class 1: 'Cardiovascular & neurology anatomical group' (27.25%) included participants using medications of the cardiovascular and nervous systems in their later years; class 2: 'Multiple anatomical group' (16.49%) and class 3: 'Antiinfectives & multiple anatomical group' (56.27%). When compared to the reference class (class 1), the risk of participants being in class 3 was slightly higher than being in class 2 if they had > 4 general practitioner visits (RRR 2.37; 95% CI 2.08, 2.71), Department of Veterans Affairs' coverage (RRR 1.59; 95% CI 1.36, 1.86), ≥ 4 chronic diseases (RRR 3.16; 95% CI 2.56, 3.90) and were frail (RRR 1.47; 95% CI 1.27, 1.69). Identification of combinations of medication use may provide opportunities to develop multimorbidity guidelines and target medication reviews, and may help reduce medication load for older individuals.


Cell seeding for small diameter ePTFE vascular grafts: a comparison between adult human endothelial and mesothelial cells.
A series of experiments was performed to compare the ability of adult human endothelial and mesothelial cells to attach and spread upon ePTFE graft material. Both cell types were harvested enzymatically and grown in culture. Two types of adhesion assay were used to assess the ability of the cultured cells to attach to ePTFE either uncoated or precoated with a variety of substrate proteins. The results showed that fibronectin, laminin, type 4 collagen and preclotted blood all greatly improve the attachment rate of endothelium to ePTFE. The extracellular matrix proteins, however, give patchy cell attachment, whereas cells seeded onto preclotted ePTFE form a virtually confluent monolayer after one hour's incubation. The matrix proteins similarly improve mesothelial attachment, although in all cases attached cells remain largely rounded up, with relatively few spreading on the surface. Mesothelial attachment to preclotted ePTFE is no better than attachment to the untreated material. It would seem that a preclotted graft seeded with endothelial cells is the combination most likely to result in a confluent monolayer within one hour.


Neoadjuvant therapy strategies for advanced gastric cancer: Current innovations and future challenges.
Gastric cancer, which has a high incidence and poor prognosis, remains a therapeutic challenge. Recently, neoadjuvant therapy has attracted increasing attention due to high recurrence rate and low survival rate after resection in most patients with advanced stage. Clinical trials show that neoadjuvant approaches confer a significant survival advantage for resectable locally advanced gastric cancer. The specific advantages of chemoradiotherapy compared with chemotherapy have not been clarified; optimal regimens and cycles, particularly in the preoperative setting, should be studied further; and trials aimed at determining the role of targeted and immunological therapies should be conducted.


Co-registration of angiography and intravascular ultrasound images through image-based device tracking.
To determine the feasibility of automated co-registration of angiography and intravascular ultrasound (IVUS) to facilitate integration of these two imaging modalities in a synchronous manner. IVUS provides cross-sectional imaging of coronary arteries but lacks overview of the vascular territory provided by angiography. Co-registration of angiography and IVUS would increase utility of IVUS in the clinical setting. Forty-nine consecutive patients undergoing surveillance for cardiac allograft vasculopathy with angiography and IVUS of the left anterior descending artery (LAD) were enrolled. A pre-IVUS angiogram of the LAD was performed followed by an ECG-triggered fluoroscopy (ECGTF) during IVUS pullback at 0.5 mm/s using an automatic pullback device. ECGTF was used to track the IVUS catheter during pullback and establish a spatial relationship to the pre-IVUS angiogram. Angio-IVUS co-registration was performed with a research prototype (Siemens Healthcare, Germany) and accuracy was evaluated by distance mismatch between angiography and IVUS images at vessel bifurcations. Median age was 54 (44.5, 67) years. The population was 82.6% male with minimal risk factors. The median (IQR) co-registration distance mismatch measured at 108 bifurcations in 42 (85%) patients was 0.35 (0.00-1.16) mm. Seven patients were excluded due to inappropriate data acquisition (n = 3) and failure of tracking (n = 4), e.g., due to overlapping sternal wires. Estimated effective radiation dose for ECGTF was 0.09 mSv. This study demonstrates the feasibility of angio-IVUS co-registration which may be used as a clinical tool for localizing IVUS cross-sections along an angiographic roadmap. © 2015 Wiley Periodicals, Inc.


Synthetic grafts for anterior cruciate ligament reconstructive surgery.
The quest for a good and durable substitute to anterior cruciate ligament (ACL) is driving scientists to explore new promising areas of research. Autologous and allogenic ligament reconstruction bring satisfactory results in managing ACL surgery although their use is associated with significant drawbacks. To overcome the limitations of biologic grafts, many artificial devices have been developed and implanted as a substitute to the native ACL over the past decades. Although many synthetic grafts used in the past have been withdrawn from the market due to early mechanical failures ultimately leading to synovitis and osteoarthritis, there is recently a resurgence of interest in the use of synthetic ligaments for ACL reconstruction. However, this new generation of artificial ligaments, despite promising initial results, have shown to produce serious side effects such as high rupture rates, insufficient tendon-bone healing and loosening. For these reasons, recent advancements in biomedical engineering are focusing on improving technical features of artificial ligaments combining mechanical properties to biocompatibility. Bioactive coatings and surface modification methods have been proposed to enhance synthetic ligament biocompatibility and promote osseointegration. The path to the development of a safe and effective artificial ligament is still full of challenges, however recent advancements are leading the way towards a tissue-engineered substitute to the native ACL.


Predicting the Risk of Bowel-Related Quality-of-Life Impairment After Restorative Resection for Rectal Cancer: A Multicenter Cross-Sectional Study.
Restorative anterior resection is considered the optimal procedure for most patients with rectal cancer and is frequently preceded by radiotherapy. Both surgery and preoperative radiotherapy impair bowel function, which adversely affects quality of life. This study aimed to report symptoms associated with and key predictors for bowel-related quality-of-life impairment. The study included a cross-sectional cohort. This was a multicenter study from 12 United Kingdom centers. A total of 578 patients with rectal cancer underwent curative restorative anterior resection between 2001 and 2012 (median, 5.25 years postsurgery). Patients completed outcome measures that assessed bowel dysfunction (low anterior resection syndrome score), incontinence (Wexner score), and quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30), plus an anchor question: "Overall how does bowel function affect your quality of life?" The response rate was 80% (462/578). Overall, 85% (391/462) of patients reported bowel-related quality-of-life impairment, with 40% (187/462) reporting major impairment. A large difference in global quality of life (22 points; p < 0.001) was reported for "none" versus "major" impairment, with greatest symptom severity being diarrhea (25 points; p < 0.001), insomnia (24 points; p < 0.001), and fatigue (20 points; p < 0.001). Regression analysis identified major impairment in 60% and 45% of patients with low rectal cancer treated with and without preoperative radiotherapy compared with 47% and 33% of middle/upper rectal cancers with and without preoperative radiotherapy. Advances in radiotherapy delivery and improvements in posttreatment symptom control, although currently of limited efficacy, imply that the content of this consent aid should be re-evaluated in 5 to 10 years. Before a restorative anterior resection, patients with rectal cancer should be informed that bowel-related quality-of-life impairment is common. The key risk factors are neoadjuvant therapy and a low tumor height. This study presents quality-of-life and functional outcome data, along with a consent aid, that will enhance this preoperative patient discussion.


HPLC-MS degradation study of E10 Sunset Yellow FCF in a commercial beverage.
Experimental evidence has shown that a beverage containing Sunset Yellow FCF (labelled as E110 in the European Union), when exposed to natural conditions of summer temperature and sunlight, losses its colour. To possibly identify the degradation pathway and collect information on the potential toxicity of the uncoloured species formed, different degradation conditions, under both oxidising and reducing environments, were simulated in laboratory. Experiments were carried out under the following conditions: (i) thermally induced degradation, (ii) visible photo induced degradation, (iii) UV-photo induced conditions in oxidising environment (addition of hydrogen peroxide, Fenton reaction) and (iv) UV-photo induced conditions in reducing environment (addition of sulphide and ascorbic acid, addition of ascorbic acid in the absence and in the presence of saccharose). Decolourisation process was observed in oxidant conditions when applying the Fenton reaction but the reaction was too quick to be progressively followed. On the other hand, it was also possible to study the degradation reaction observed in reducing conditions in the presence of ascorbic acid. The HPLC-MS results gave evidence for the cleavage of the double bond and the protonation of the azo groups. The loss of colour is therefore not due to a mineralization process but to the formation of a dimeric form of 5-amino-6-hydroxy-2-naphthalene sulfonate and, likely, of p-amino-benzensulfonate.


[Diagnosis and treatment of inflammatory myofibroblastic tumor of the chest].
To explore the causes, clinic diagnosis, treatment and prognosis of inflammatory myofibroblastic tumor (IMT) of the chest. The clinical data of 12 patients with IMT were retrospectively analyzed including 9 male and 3 female patients aged 36 to 81 years (mean 60.08 years). Five patients underwent pulmonary lobectomy and mediastinal lymph node dissection, 1 had partial lobectomy, 1 had mediastinal tumor resection and costectomy, and 2 received conservative treatment. All the surgical patients recovered after surgery without lymph node metastasis detected by pathological examinations. In the follow-up lasting for 2 months to 5 years, no recurrence or metastasis occurred in these cases. In the 2 cases having conservative treatment, the tumor remained unchanged in one case at 3 month of follow-up and disappeared in the other case. IMT in the chest is a rare benign tumor with a low incidence rate and malignancy. Pathological examination is reliable for definite diagnosis. Surgical operation is the primary therapeutic approach. All IMT patients should be closely followed up after the treatment.


Limitation of impedance plethysmography in assessing efficacy of dihydroergotamine-heparin prophylaxis of deep vein thrombosis.
The sensitivity of impedance plethysmography (IPG) for diagnosing deep vein thrombosis was evaluated in the presence of dihydroergotamine, an agent with significant venoconstrictor activity. In a prospective, randomized, controlled clinical trial, 105 patients undergoing total hip replacement surgery were investigated to evaluate the thromboprophylactic efficacy of DHE-Heparin using IPG and 125I-Fibrinogen Leg Scanning to monitor the incidence of DVT. Retrospective analysis of the IPG data indicated that DHE-Heparin impaired the sensitivity of impedance plethysmography by decreasing venous capacitance and venous outflow. Although the patient sample size was relatively small, the results showed trends which suggested that the utility of impedance plethysmography for diagnosing DVT was limited in the presence of a vasoactive agent. Alternate noninvasive diagnostic methods may need to be considered in select patients receiving concomitant medications possessing venoconstrictor activity.


[Effect of the natriuretic factor obtained from arterial blood of dogs on cardio- and hemodynamics in experimental studies].
The natriuretic factor, inhibiting Na-K-ATPase, exerts a stable positive inotropic and negative chronotropic effect as a result of its single administration in a dose stimulating the natriuretic activity of the kidneys. It also decreases the overall peripheral vascular resistance. The mean arterial pressure slightly changes.


SmLMWPTP, a teleost low molecular weight protein tyrosine phosphatase, inhibits the immune response of peripheral blood leukocytes in a manner that depends on the conserved P-loop.
Protein tyrosine phosphatases (PTPs) are a family of enzymes that play a key role in cellular signal transduction. Low molecular weight PTPs (LMWPTPs) are a subfamily of PTPs that are characterized by the presence of a conserved phosphate-binding loop (P-loop) with the signature sequence of (V/I)CXGNXCRS. To date, very little study on teleost LMWPTPs has been documented, and, as a result, the function of LMWPTPs in fish is essentially unknown. In this study, we identified a LMWPTP from turbot (Scophthalmus maximus) and examined its biological activity and functionality. The turbot LMWPTP (SmLMWPTP) is composed of 158 residues and possesses a typical P-loop sequence in the form of (12)VCLGNICRS(20). Purified recombinant SmLMWPTP (rSmLMWPTP) exhibited apparent phosphatase activity, which was optimal at pH 5 and 50°C. The activity of SmLMWPTP was abolished when C13 and, in particular, R19 of the P-loop were mutated. SmLMWPTP expression was detected in a wide range of tissues and upregulated by bacterial and viral infection. Subcellular localization analysis showed that SmLMWPTP was secreted by peripheral blood leukocytes (PBL) into the extracellular milieu. When PBL were treated with rSmLMWPTP, the cells exhibited significant reductions in (i) proliferative and respiratory burst activity, (ii) expression levels of multiple immune relevant genes, and (iii) phagocytic activity. In contrast, the mutant SmLMWPTP bearing R19 mutation had no effect on PBL activity. Taken together, these results indicate that SmLMWPTP is a secreted PTP that exerts a negative regulatory effect on the innate immune response of PBL in a manner that depends on the structural integrity of the P-loop.


Illness perceptions in coronary heart disease. Sociodemographic, illness-related, and psychosocial correlates.
This study examined illness perceptions (IP) and their correlates in coronary heart disease (CHD). The sample of the questionnaire study (n = 3130 at baseline and n = 2745 at 1-year follow-up, aged 45-74 years) was drawn from the drug reimbursement register, which covers persons with various drug-treated conditions. Independent variables were CHD severity and history, vicarious experiences, and psychosocial resources. Men attributed their CHD more often to risk behaviours and internal factors (own attitude/behaviour), while women perceived stress as the cause of their CHD more often. Women also perceived more symptoms associated with CHD but reported less severe consequences. CHD severity was the most important correlate of IP and also predicted change in IP at the follow-up. Stronger perceived competence was related to weaker illness identity, stronger control/cure, and less severe consequences. Although disease-related factors are powerful correlates of CHD-related illness cognitions, also social and psychosocial factors are related to IP.


The prognostic value of relative renal function greater than 51% in the pelvi-ureteric junction-obstructed kidney on 99mtechnetium mercaptoacetyltriglycine study.
Obstructed kidneys with relative function (RRF) estimates >50% are occasionally noted in (99m)technetium mercaptoacetyltriglycine renal studies. It is thought that increased RRF might confer some benefit and/or permit delayed intervention. We compared the RRF and absolute renal function, as defined by effective renal plasma flow (ERPF), of obstructed kidneys in the ranges >51%, 40%-50% and <40% RRF before and after pyeloplasty. Twenty children, median age 13.5 months (range 3 weeks-126 months), satisfied criteria for the diagnosis of PUJ obstruction and estimated function >51% (group 1). Their pre- and post-intervention data were compared with 21 children, median age 2 months (range 1 week-126 months), with PUJ obstruction and 40%-50% RRF (group 2); and 21, median age 6 months (range two days-110 months), with RRF below 40% (group 3). Kidneys showing signs of continuing obstruction after surgery were excluded. Final ERPF was negatively related to age: younger children, and those with a higher preoperative ERPF, recovered better than older children and those with a lower ERPF (p<0.05). Pre- and postoperative mean ERPF in group 1 was 76 (range 21-203) and 102 (6-240) ml/min/1.73 msq respectively. In group 2, these values were 75.2 (30-187) and 130.9 (44-306) ml/min/1.73 msq, and they were 42.6 (5-179) and 80.2 (17-205) ml/min/1.73 msq in group 3. When adjustment was made for preoperative ERPF, there was no evidence that RRF grouping was related to ERPF outcome. The postoperative ERPF of seven of 20 kidneys from group 1 (>51%) was lower than the ERPF before surgery compared to 2/21 in group 2 and 4/21 in group 3, but these differences were not statistically significant (p=0.25). Most kidneys in each functional range improved when obstruction was relieved. An RRF >51% in the obstructed kidney was not always prognostically beneficial, and may be a warning of impending decompensation in a minority.


[Multiple human cord blood transfusion for inducing low immune response].
To investigate and evaluate a clinically perspective way of inducing transplantation tolerance. Multi-cord blood transfusion was performed before kidney transplantation in 20 cases. Donor-specific mixed lymphocyte reaction(MLR) and allograft rejection were observed and studied. The donor-specific MLR was suppressed in every recipient. No allograft rejection took place in the cord blood transfusion group three months after kidney transplantation. Multi-cord blood transfusion is a practical way of inducing transplantation tolerance.


Factors Related to the Use of Topical vs. Oral NSAIDs for Sprains, Strains, and Contusions in a Senior Population: A Retrospective Analysis of Administrative Claims Data.
Research to date on sprains, strains, and contusions has focused mainly on the analysis of sports-related injuries, occupational injuries, injuries resulting from automobile accidents, and severe injuries that result in inpatient hospital stays. Little is known about real-world acute sprains, strains, and contusions in an aging population. Patients may be treated with over-the-counter, oral, non-steroidal anti-inflammatory drugs (NSAIDs) for acute sprains, strains, and contusions or may require the use of prescription NSAIDs. For sprains, strains, and contusions treated with prescription NSAIDs, the choice of topical administration or oral administration likely depends on a number of factors such as age and comorbid conditions. The objective of the study was to identify factors associated with the use of a prescription topical NSAID or a prescription oral NSAID for the treatment of sprains, strains, and contusions among patients aged 65-89 years enrolled in the Medicare Advantage with Prescription Drug plan. The study sample was selected from the Humana Research Database (Louisville, KY, USA). Study subjects were identified as patients enrolled in Medicare Advantage with Prescription Drug plans, aged 65-89 years, having a medical claim with an International Classification of Diseases, Ninth Revision, Clinical Modification indicative of an acute sprain, strain, and contusion between 1 January, 2010 and 31 March, 2014 (identification period). The date of the first claim was considered the index date, and subjects were required to have 12 months of continuous enrollment before the index date and a minimum of 3 months continuous enrollment after the index date. Prescription NSAID use during the 3 months after the index sprain, strain, and contusion diagnosis was required for study inclusion and was identified based on a pharmacy claim for a topical or an oral NSAID. Patients with prescription NSAID use leading up to the sprains, strains, and contusions were excluded. Potential factors related to the use of a topical vs. oral NSAID were identified using stepwise logistic regression with backward elimination. After applying the inclusion and exclusion criteria, 42,283 patients were prescribed an oral or topical NSAID (39,294 oral; 2989 topical) within 3 months of the index sprain, strain, and contusion diagnosis. After applying stepwise logistic regression, and retaining variables with statistically significant parameter estimates (p < 0.05), use of topical NSAIDs was higher among female individuals [odds ratio and 95% confidence interval = 1.34 (1.24-1.45)], and appeared to increase with age [odds ratio = 1.04 (1.04-1.05)]. Topical NSAID use was lower in the Midwest region [odds ratio = 0.85 (0.77-0.94)] in comparison to the Southern region. Clinical factors associated with topical NSAID use included Elixhauser Comorbidity Index score [odds ratio = 1.06 (1.04-1.09)], medication burden [odds ratio = 1.06 (1.04-1.08), pill burden [odds ratio = 1.02 (1.01-1.03), specific comorbid conditions, including site-specific osteoarthritis of the upper arm [odds ratio = 2.34 (1.19-4.60)], ankle/foot [odds ratio = 1.46 (1.14-1.87)], or lower leg [odds ratio = 1.21 (1.07-1.36)], myofascial pain [odds ratio = 1.31 (1.21-1.42)], gastrointestinal/hepatic disorders [odds ratio = 1.15 (1.05-1.25)], systemic/central pain [odds ratio = 1.12 (1.01-1.23)], and cataracts [odds ratio = 1.10 (1.02-1.20)]. Conversely, a diagnosis of diabetes mellitus was related to use of an oral NSAID rather than a topical NSAID [odds ratio = 0.86 (0.78-0.94)]. Diagnosis of the index sprain, strain, and contusion in an emergency department instead of a physician's office was also associated with oral NSAID use [odds ratio = 0.42 (0.37-0.47)]. Topical NSAIDs were used less often than oral NSAIDs following a sprain, strain, or contusion. Age, medication burden, pill burden, evidence of gastrointestinal disorder, and evidence of certain pain-related conditions were significant factors associated with topical NSAID as opposed to oral NSAID use. In comparison to oral NSAIDs, topical NSAIDs were more likely to be prescribed in a physician's office than an emergency department, possibly because a patient's physician has a better understanding of the patient's concomitant medications and comorbidities. Although topical NSAIDs were more likely to be used than oral NSAIDs in patients with gastrointestinal disorders, the use of oral NSAIDs among patients with gastrointestinal bleeding was substantial.


Prechemistry versus preorganization in DNA replication fidelity.
The molecular origin of nucleotide insertion catalysis and fidelity of DNA polymerases is explored by means of computational simulations. Special attention is paid to the examination of the validity of proposals that invoke prechemistry effects, checkpoints concepts, and dynamical effects. The simulations reproduce the observed fidelity in Pol β, starting with the relevant observed X-ray structures of the complex with the right (R) and wrong (W) nucleotides. The generation of free energy surfaces for the R and W systems also allowed us to analyze different proposals about the origin of the fidelity and to reach several important conclusions. It is found that the potential of mean force (PMF) obtained by proper sampling does not support QM/MM-based proposals of a large barrier before the prechemistry state. Furthermore, examination of dynamical proposals by the renormalization approach indicates that the motions from open to close configurations do not contribute to catalysis or fidelity. Finally we discuss and analyze the induced fit concept and show that, despite its importance, it does not explain fidelity. That is, the fidelity is apparently due to the change in the preorganization of the chemical site, as a result of the relaxation of the binding site upon binding of the incorrect nucleotide. Finally and importantly, since the issue is the barrier associated with the enzyme-substrate (ES)/DNA complex at the chemical transition state and not the path to this complex formation (unless this path involves rate determining steps), it is also not useful to invoke checkpoints while discussing fidelity.


Downregulation of plasma microRNA-29c-3p expression may be a new risk factor for diabetic retinopathy.
Circulation miRNAs have emerged as new biomarkers for identifying and monitoring the microvascular complications of diabetes. The aim of this study is to evaluate the levels of five candidate miRNAs (miR-29c-3p, miR-18a, miR-31, miR-181 and miR-20a) in patients with diabetic retinopathy (DR) and their relationship with disease severity. The study included 31 diabetes patients without DR (NDR group), 68 patients with DR (DR group) and 30 healthy controls (HC group). Twenty-five of patients with DR were proliferative DR (PDR group) and 43 were non-proliferative DR (NPDR group) patients. Metabolic parameters and serum vascular endothelial growth factor (VEGF) levels of all participants were measured. Circulating miRNAs levels were determined by quantitative real-time PCR. Fundus examinations of all patients were performed by a single ophthalmologist. VEGF levels were significantly higher in the NDR, and DR groups compared to HC group (P=0.011 and P=0.014, respectively). Plasma miR-29c-3p was downregulated in diabetic patients with retinopathy and without retinopathy. This downregulation was more prominent in diabetic patients without retinopathy compared to those with retinopathy (P=0.016). There was no significant difference in plasma levels of miR-18a, miR-20a, miR-18a and miR-31 between diabetic subjects with and without retinopathy (P>0.05). There was no correlation between DR severity and the levels of miRNAs (P>0.05). In multivariate logistic regression analysis, it was found that changes in plasma miR-29c-3p expression of diabetic patients increased DR risk independent of other risk factors. Plasma miR-29c-3p expression is downregulated in diabetic patients with and without retinopathy, and changes in this miRNA are an independent risk factor for the development of DR.


Influence sexual dimorphism on the persistence of blood parasites in infected Calomys callosus.
Gender has long been known to be a contributory factor in the incidence and progression of disorders associated with immune system disregulation. The aims of this experiment were to verify the influences of sexual dimorphism on the persistence of blood parasites out of the acute phase of infection. Male and female Calomys callosus were separated and infected with two strains of Trypanosoma cruzi, and let age until 120 days. Xenogiagnostic, culture of organs and blood, histopathology and lytic antibody percentages were evaluated on late chronic phase. Xenodiagnosis, hemoculture and lytic antibody percentages were positive from 45 until 120 days. For both strains in adrenal and heart, amastigote burdens were present until 45 days, scarcely found on 60 days and absent on 120 days. Steroid hormones, although having a protective role, does not enable animals to get completely rid of the infection. Even without showing apparent signs of pathological unbalance, parasites persists, hidden throughout the host's body.


[Control of tuberculosis in Nepal. A project. Initial results, experiences].
2,124 persons were examined in 16 months. 328 of these were tuberculosis patients requiring treatment. When treated, 74%, 81% and 97% of the patients showed conversion of sputum after 2, 4 and 6 months, respectively. Sensitivity tests (n = 223) yielded 19% monoresistances and 5% resistances against 2 drugs. 87% of the patients took their tablets regularly; 8.7% discontinued the treatment.


Effect of antilymphocyte globulin on granulocyte precursors in aplastic anaemia.
Granylocyte colony forming units (CFU-C) were studied in 22 patients with severe aplastic anaemia before and after treatment with antilymphocyte globulin (ALG). Nine patients showed a clinical response to ALG characterized by a rise in the granulocyte count to over I X 10(9)/1 within 30 d. These patients were distinguished in vitro from non-responders by an increase in CFU-C numbers after incubation of bone marrow cells with ALG, and by the presence of inhibitors of normal CFU-C in the serum in six out of seven patients tested. In responding patients bone marrow CFU-C rose while most non-responding patients showed no change or a fall in CFU-C after treatment. In addition in three out of four responding patients examined serum inhibitors disappeared after treatment. The horse ALG used in this study also stimulated normal CFU-C in vitro. This evidence is contrary to the hypothesis that ALG stimulates CFU-C in aplasia by inactivating an abnormal suppressor lymphocyte population. The nature of the stimulation by ALG remains unclear. But in practice the effect of ALG on bone marrow cells and study of CFU-C inhibitors in serum could be used to select patients likely to respond to ALG treatment.


Radio-guided localization of clinically occult breast lesions (ROLL): a DGH experience.
Wire-guided localization (WGL) of clinically occult breast lesions is a well established technique. The aim of this study was to evaluate radio-guided localization (ROLL) within the breast screening service of a district general hospital. The study group comprised 70 women who underwent ROLL under US and stereotaxis. This required an injection of Technetium-labelled colloidal albumen into the impalpable breast lesion. The women then proceeded to theatre, where localization was achieved with the use of a gamma probe. The lesion was identified by the presence of a high signal, caused by the injected isotope. The results of 70 consecutive cases in which a breast lesion was localized using ROLL were compared with the results of the latest 70 WGLs. All 140 lesions were successfully localized. However, the change in technique from WGL to ROLL offered significant benefits to patients. Our study demonstrated that ROLL is a practical and reliable localization technique. It can be implemented in hospital units without using valuable gamma camera time. The cost compares well with WGL. There is an improved cosmetic outcome for patients, and the very small quantity of radioactivity used is safe for both patients and staff.