Inadequate programming, insufficient communication and non-compliance with the basic principles of maternal death audits in health districts in Burkina Faso: a qualitative study.
Implementation of quality maternal death audits requires good programming, good communication and compliance with core principles. Studies on compliance with core principles in the conduct of maternal death audits (MDAs) exist but were conducted in urban areas, at the 2nd or 3rd level of the healthcare system, in experimental situations, or in a context of skills-building projects or technical platforms with an emphasis on the review of "near miss". This study aims to fill the gap of evidence on the implementation of MDAs in rural settings, at the first level of care and in the routine care situation in Burkina Faso. We conducted a multiple-case study, with seven cases (health districts) chosen by contrasted purposive sampling using four criteria: (i) the intra-hospital maternal mortality rates for 2013, (ii) rural versus urban location, (iii) proofs of regular conduct of maternal death audits (MDAs) as per routine health information system, and (iv) the use of district hospital versus regional hospital for reference when the first mentioned does not exist. A review of audit records and structured and semi-structured interviews with staff involved in MDAs were conducted. The survey was conducted from 27 April to 30 May of 2015. The results showed that maternal death audits (MDAs) were irregularly scheduled, mostly driven by critical events. Overall, preparing sessions, communication and the conduct of MDAs were most of the time inadequate. Confidentiality was globally respected during the clinical audit sessions. The principle of "no name, no shame, and no blame" was differently applied and anonymity was rarely preserved. Programming, communication, and compliance with the basic principles in the conduct of maternal death audits were inadequate as compared to the national standards. Identifying determinants of such shortcomings may help guide interventions to improve the quality of clinical audits. La mise en œuvre d'audits de décès maternels de qualité nécessite une bonne programmation, une bonne communication et le respect des principes fondamentaux. Des études sur le respect des principes fondamentaux existent mais ont été menées dans les zones urbaines, le 2ème ou 3ème niveau du système de santé, dans des situations expérimentales, un contexte de projets de renforcement des compétences ou de plates-formes techniques, en mettant l'accent sur la revue des «near miss». Cette étude vise à combler le manque d'information sur la programmation et le respect des principes fondamentaux concernant le milieu rural, le niveau du système de santé qui est. le district sanitaire et la situation de routine au Burkina Faso. MéTHODOLOGIE: Nous avons mené une étude de cas multiple dans 7 établissements de santé sélectionnés par échantillonnage raisonné contrasté selon 4 critères: milieu urbain ou rural, taux de mortalité maternelle dans les établissements de santé en 2013 (les données de l'année 2014 n'étant pas complètes à la rédaction du protocole), la déclaration des audits de décès maternels dans le système de surveillance nationale, le recours ou non par le district choisi à un centre hospitalier régional pour les soins complémentaires de premier niveau (normalement offerts à l'hôpital de district s'il existe). Une revue des dossiers d'audits, ainsi que des entretiens directifs, semi-directifs auprès du personnel impliqué dans les soins de maternité ont été réalisés. L'enquête s'est. déroulée du 27 Avril au 30 Mai 2015. RéSULTATS: Les résultats montrent que les revues des décès maternels ont été irrégulièrement programmées, de façon espacée et très souvent au gré des évènements. La préparation, la conduite des séances et la communication après les séances ont été défaillantes. La confidentialité au sein du groupe d'auditeurs a été respectée tandis que le niveau de respect du principe de « no name, no shame, no blame » a varié d'une structure à une autre. Enfin, l'anonymat a été le moins respecté. La programmation, la communication et le respect des principes fondamentaux ont connu des défaillances par rapport aux normes mais de façon variable d'une structure à une autre. L'identification des déterminants de ces insuffisances pourront aider à l'orientation des interventions visant l'amélioration de l'activité des audits de décès maternels au niveau district de santé.


Hemodynamic effects of peri-operative statin therapy in on-pump cardiac surgery patients.
Peri-operative statin therapy in cardiac surgery cases is reported to reduce the rate of mortality, stroke, postoperative atrial fibrillation, and systemic inflammation. Systemic inflammation could affect the hemodynamic parameters and stability. We set out to study the effect of statin therapy on perioperative hemodynamic parameters and its clinical outcome. In a single center study from 2006 to 2007, peri-operative hemodynamic parameters of 478 patients, who underwent cardiac surgery with cardiopulmonary bypass, were measured. Patients were divided into those who received perioperative statin therapy (n = 276; statin group) and those who did not receive statin therapy (n = 202; no-statin group). The two groups were compared together using Kolmogorov-Smirnov-Test, Fisher's-Exact-Test, and Student's-T-test. A p value < 0.05 was considered as significant. There was no significant difference in the preoperative risk factors. Onset of postoperative atrial fibrillation was not affected by statin therapy. Extended hemodynamic measurements revealed no significant difference between the two groups, apart from Systemic Vascular Resistance Index (SVRI). The no-statin group had a significantly higher SVRI (882 ± 206 vs. 1050 ± 501 dyn s/cm5/m2, p = 0.022). Inotropic support was the same in both groups and no significant difference in the mortality rate was noticed. Also, hemodynamic parameters were not affected by different types and doses of statins. Perioperative statin therapy for patients undergoing on-pump coronary bypass grafting or valvular surgery, does not affect the hemodynamic parameters and its clinical outcome.


[Use of a standard radioactive paste in the study of esophago-gastric kinesis (author's transl)].
The behaviour of esophago-gastric kinesis has been studied comparatively by administering BaSO4 and normal food respectively, labelled with 1 mCi of 99mTc-DTPA. The results are discussed and the differences observed are stressed. These confirm the non-physiological nature of the conventional opaque paste employed in X-ray diagnosis.


Cytotoxic triterpenoid saponins from Clematis tangutica.
Eight previously undescribed oleanane-type triterpenoid saponins, clematangoticosides A-H, together with eight known saponins, were isolated from the whole plants of Clematis tangutica (Maxim.) Korsh. Their structures were elucidated by extensive spectroscopic analysis, in combination with chemical methods (acid hydrolysis and mild alkaline hydrolysis). Clematangoticosides D-G were found to be unusual 23, 28-bidesmosidic glycosides. The cytotoxic activities of all of the isolated saponins were evaluated against the four human cancer cell lines SGC-7901, HepG2, HL-60 and U251MG. Clematoside S, sapindoside B, kalopanax saponin A, and koelreuteria saponin A exhibited cytotoxicity against all of the test cancer cell lines with IC50 values in the range of 1.88-27.20 μM, while clematangoticoside D and F showed selective cytotoxicity against SGC-7901 with IC50 values of 24.22 and 21.35 μM, respectively.


Use of granules and free salts for Fe and Zn fortification of leafy vegetables: Improvements in trace element bioaccessibility and fulfillment of Dietary Reference Intakes.
Leafy vegetables represent an excellent dietary source of trace elements such as Fe and Zn. Nevertheless, Fe and Zn bioaccessibility can lessen due to a high concentration of anti-nutritional compounds. The encapsulation of Fe and Zn salts as granules could be used to fortify these leafy vegetables. Three leafy vegetables, spinach, Swiss chard and Ethiopian mustard were fortified with iron sulfate and zinc sulfate as granules and free salts in order to test the improvements in the bioaccessibility and fulfillments of DRIs. Fe and Zn granules were prepared in a fluidized bed granulator. A probabilistic analysis was performed, using experimental data, to assess bioaccessible intake and fulfillments of DRIs in European populations. Fe contents ranged between 4.8 mg/100 g of Ethiopian mustard to 157.4 mg/100 g of spinach. Fe and Zn bioaccessibility percentages were low for Swiss chard and spinach without fortification. Fortification with granules improved Fe bioaccessibility of these latter vegetables (196 and 223 mg/100 g). Zn contents in samples without fortification ranged between 2.3 mg/100 g for Ethiopian mustard and 7.4 mg/100 g for spinach. Zn fortification as granules improved Zn bioaccessibility for the three vegetables studied. Thus, Zn bioccessible concentrations ranged between 17.4 and 108 mg/100 g for the solubility assay and between 5.9 and 31.1 mg/100 g for the dialyzability assay. Besides, the probability analysis showed that fortification had a better performance in meeting DRIs for those populations with higher consumption levels of leafy vegetables. The probability analysis demonstrated that fortification can be a suitable strategy to meet DRIs for both trace elements, which was especially remarkable for Fe. Fortification with granule was more effective in most the cases, although for Ethiopian mustard, free salt of Fe showed a better performance.


California's methane super-emitters.
Methane is a powerful greenhouse gas and is targeted for emissions mitigation by the US state of California and other jurisdictions worldwide1,2. Unique opportunities for mitigation are presented by point-source emitters-surface features or infrastructure components that are typically less than 10 metres in diameter and emit plumes of highly concentrated methane3. However, data on point-source emissions are sparse and typically lack sufficient spatial and temporal resolution to guide their mitigation and to accurately assess their magnitude4. Here we survey more than 272,000 infrastructure elements in California using an airborne imaging spectrometer that can rapidly map methane plumes5-7. We conduct five campaigns over several months from 2016 to 2018, spanning the oil and gas, manure-management and waste-management sectors, resulting in the detection, geolocation and quantification of emissions from 564 strong methane point sources. Our remote sensing approach enables the rapid and repeated assessment of large areas at high spatial resolution for a poorly characterized population of methane emitters that often appear intermittently and stochastically. We estimate net methane point-source emissions in California to be 0.618 teragrams per year (95 per cent confidence interval 0.523-0.725), equivalent to 34-46 per cent of the state's methane inventory8 for 2016. Methane 'super-emitter' activity occurs in every sector surveyed, with 10 per cent of point sources contributing roughly 60 per cent of point-source emissions-consistent with a study of the US Four Corners region that had a different sectoral mix9. The largest methane emitters in California are a subset of landfills, which exhibit persistent anomalous activity. Methane point-source emissions in California are dominated by landfills (41 per cent), followed by dairies (26 per cent) and the oil and gas sector (26 per cent). Our data have enabled the identification of the 0.2 per cent of California's infrastructure that is responsible for these emissions. Sharing these data with collaborating infrastructure operators has led to the mitigation of anomalous methane-emission activity10.


Does trainee involvement affect anticipatory guidance in well-child care?
Studies demonstrate gaps in anticipatory guidance during well-child visits, but none consider academic teaching hospitals where physician trainees also provide counseling. We prospectively assessed parental perception of anticipatory guidance at the outpatient clinic of an academic teaching hospital. Parents of patients newborn to <60 months old completed questionnaires regarding providers seen and anticipatory guidance preferences. Of 204 parents, 40% saw the child's primary attending alone. There was no association between providers seen and the number of topics covered. Seeing the child's primary attending alone increased the odds that parents' priority topics were covered compared with another attending (odds ratio [OR] = 0.31; 95% confidence interval [CI] = 0.11-0.90) or the addition of a resident (OR = 0.35; 95% CI = 0.16-0.77) or medical student (OR = 0.33; 95% CI = 0.12-0.90). Priority anticipatory guidance is covered only one third as often when the well-child visit is not conducted by the primary attending. When involving trainees, continuity of care and parental concerns must be emphasized.


A nerve conduit filled with Wnt5a-loaded fibrin hydrogels promotes peripheral nerve regeneration.
Peripheral nerve injury is a significant clinical problem with a substantial impact on quality of life, for which no optimal treatment has been found. This study aimed to analyze the effect and mechanism of Wnt5a-loaded fibrin hydrogel on a 10-mm rat sciatic nerve defect. The Wnt5a-loaded fibrin hydrogel was synthesized by mixing a Wnt5a solution with thrombin and fibrinogen solutions. The loading capacity and release profile of Wnt5a-loaded fibrin hydrogel and the effect of Wnt5a on Schwann cells were evaluated in vitro. We also assessed the in vivo repair status via histological analysis of the regenerative nerve and gastrocnemius muscle, electrophysiological examination, gait analysis, and muscle wet weight. We developed a nerve conduit filled with Wnt5a-loaded fibrin hydrogel (Fn) as a sustained-release system to repair a 10-mm rat sciatic nerve defect. In vitro, Wnt5a could promote SC proliferation and the gene expression of vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and cholinergic neurotrophic factor (CNTF), as well as the protein secretion of VEGF and NGF. In vivo, the Wnt5a/Fn group was superior to the hollow, fibrin hydrogel, and Wnt5a groups in terms of axonal growth, myelination, electrophysiological recovery, target organ innervation, and motor function recovery 12 weeks after the operation. The Wnt5a/Fn nerve conduit can promote peripheral nerve defect regeneration, with potential clinical applications. The mechanism for this may be the facilitation of multiple neurotrophin secretion, combining vascularization and neurotrophic growth cues.


Possibilities of retention prediction in fast gradient liquid chromatography. Part 1: Comparison of separation on packed fully porous, nonporous and monolithic columns.
Due to ever increasing importance of short analysis times in modern HPLC practice, fast gradient elution is becoming widely used both in one-dimensional and two-dimensional separations, especially in the second dimension where the speed of separation is of primary importance. For method development and optimization, prediction of retention in gradient elution from the isocratic data is very important. This is principally possible using the well-established theory of gradient elution, especially for reversed-phase separations. Feasibility of these approaches has been proven in conventional liquid chromatography and commercial prediction software is available for this purpose. However, fast gradient chromatography employing short columns and gradient times in between 1 and 2 min or even less, impose additional stringent demands on the accuracy of prediction, due to rapid changes in mobile phase composition and increased role of extra-column contributions and instrumental dwell volume on the retention. In the present work, possibilities of prediction of the gradient elution times from the isocratic data measured only at two mobile phase concentrations were investigated in fast chromatography of alkylbenzenes, phenylurea and triazine pesticides on five columns differing in lengths: two monolithic ones and three packed with particles of different size. In the second dimension, gradient times are strongly restricted by the short cycle frequency. The effects of the flow-rate on the elution times, on the accuracy of their prediction and on peak capacity were studied under time constraint conditions. Gradient theory can be useful for the optimization of fast gradients.


Platelet count as a potential predictor in refractory Takayasu arteritis.
Platelet parameters have been recognized as important markers for disease severity in various types of diseases. The aim of our study was to investigate whether platelet count could be used as a potential predictor of refractory Takayasu arteritis (TAK). In this retrospective study, fifty-seven patients were selected as development data group to identify the associated risk factors and potential predictors of refractory TAK. Ninety-two TAK patients were included in the validation data group to verify the predictive value of platelet count for refractory TAK. Refractory TAK patients had higher levels of platelet (PLT) than non-refractory TAK patients (305.5 vs. 272.0 × 109/L, P = 0.043). For PLT, the best cut-off value was 296.5 × 109/L to predict refractory TAK. Elevated PLT (> 296.5 × 109/L) was found to be statistically related to refractory TAK (OR [95%CI] 4.000 [1.233-12.974], p = 0.021). In the validation data group, the proportion of refractory TAK in patients with elevated PLT was significantly higher than that in patients with non-elevated PLT (55.6% vs. 32.2%, P = 0.037). The 1-, 3- and 5-year cumulative incidence of refractory TAK were 37.0%, 44.4% and 55.6% in patients with elevated PLT, respectively. Elevated PLT (p = 0.035, hazard ratio (HR) 2.106) was identified as a potential predictor of refractory TAK. Clinicians should pay close attention to platelet levels in patients with TAK. For TAK patients with PLT greater than 296.5 × 109/L, closer monitoring of the disease and comprehensive assessment of disease activity are recommended to be alert to the occurrence of refractory TAK.


A survey of knowledge, attitudes, barriers and support needs in providing hepatitis B care among GPs practising in Australia.
In Australia, only 22% of people with chronic hepatitis B (CHB) are clinically managed; and a national effort is engaging primary care workforce in providing CHB-related care. This study explored CHB-related knowledge, attitudes, barriers and support needs of general practitioners (GPs). A survey was sent to a random sample of 1,000 Australian GPs in April- October 2018; 134 of 978 eligible GPs completed the questionnaire (14%). Respondents had high knowledge of at-risk populations (> 79%) and hepatitis B serology (82%), and most saw hepatitis B testing and monitoring as part of their work (95% and 86%, respectively). However, the survey revealed low knowledge, awareness and intention with respect to hepatitis B treatment: 23% correctly understood treatment initiation; 40% were aware that treatment for CHB could be dispensed in the community; 23% agreed that prescribing was part of their work. Lack of time was considered the greatest barrier (38%) and clear guidelines was the most important facilitator to providing care (72%). Interventions are needed to generate interest and skills to provide CHB-related care by GPs.


Systemic antibiotic therapy on multiple intracerebral abscesses of unknown origin.
A 68-year old patient presented with increasing right-sided weakness, dysarthria, pyrexia and a deteriorating general condition. CT and MRI showed about 20 round hyperdense lesions with peripheral enhancement of contrast material up to 1.5 cm in diameter. Antibiotic triple-therapy using ceftriaxone, gentamycin and metronidazole for 39 days and followed by antibiotic double-therapy using ceftriaxone and metronidazole for a further 22 days resulted in a radiologically proven reduction of the abscesses to very small remnants which disappeared completely during the follow-up period of two years. Simultaneously the general condition of the patient improved significantly. Repeated attempts at isolation of bacteria, fungi, protozoa and parasites from a subdural empyema failed. The histological examination of an abscess, which was entirely removed on occipital craniotomy, showed a structure resembling actinomycosis.


Simultaneous anterior and posterior synovectomies for treating diffuse pigmented villonodular synovitis.
The current treatment methods for diffuse intraarticular or extraarticular type pigmented villonodular synovitis (PVNS) include arthroscopic synovectomy or staged anterior and posterior open synovectomies. However, it is unclear whether simultaneous anterior and posterior synovectomies achieve local control and recovery of function. We therefore determined the recurrence rate and function in patients with diffuse PVNS treated with anterior and posterior synovectomies and adjuvant radiotherapy. We retrospectively reviewed all 19 patients with diffuse PVNS involving the knee treated with anterior and posterior synovectomies and adjuvant radiotherapy between January 2001 and November 2007. From the records, we determined local recurrence and Tegner-Lysholm scores. The minimum followup was 42 months (median, 98 months; range, 42-143 months). Postoperative MRI revealed residual tumor in five of the 19 patients, although three had no disease progression during followup and had knee scores of 86 to 90. Two patients had recurrences at 6 and 9 months with knee scores of 88 at 42 months and 90 at 68 months. The mean Tegner-Lysholm knee score improved from 59 to 93 points. Mean maximum extension and flexion angles improved from 11° to 2° and from 76° to 127°, respectively. Compared with the literature, simultaneous anterior and posterior synovectomies associated with postoperative radiotherapy provided rates of residual or recurrent tumor and knee function recovery comparable to that with staged synovectomies reported in the literature. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment.
Ribonucleotide reductase (RR) is a key enzyme in tumor proliferation, especially its subunit-RRM2. Although there are multiple therapeutics for tumors, they all have certain limitations. Given their advantages, traditional Chinese medicine (TCM) monomers have become an important source of anti-tumor drugs. Therefore, screening and analysis of TCM monomers with RRM2 inhibition can provide a reference for further anti-tumor drug development. To screen and analyze potential anti-tumor TCM monomers with a good binding capacity to RRM2. The Gene Expression Profiling Interactive Analysis database was used to analyze the level of RRM2 gene expression in normal and tumor tissues as well as RRM2's effect on the overall survival rate of tumor patients. TCM monomers that potentially act on RRM2 were screened via literature mining. Using AutoDock software, the screened monomers were docked with the RRM2 protein. The expression of RRM2 mRNA in multiple tumor tissues was significantly higher than that in normal tissues, and it was negatively correlated with the overall survival rate of patients with the majority of tumor types. Through literature mining, we discovered that berberine, ursolic acid, gambogic acid, cinobufagin, quercetin, daphnetin, and osalmide have inhibitory effects on RRM2. The results of molecular docking identified that the above TCM monomers have a strong binding capacity with RRM2 protein, which mainly interacted through hydrogen bonds and hydrophobic force. The main binding sites were Arg330, Tyr323, Ser263, and Met350. RRM2 is an important tumor therapeutic target. The TCM monomers screened have a good binding capacity with the RRM2 protein.


Method, accuracy and limitation of computer interaction in the operating room by a navigated surgical instrument.
This article describes a new interaction device for surgical navigation systems--the so-called navigation mouse system. The idea is to use a tracked instrument of a surgical navigation system like a pointer to control the software. The new interaction system extends existing navigation systems with a microcontroller-unit. The microcontroller-unit uses the existing communication line to extract the needed 3D-information of an instrument to calculate positions analogous to the PC mouse cursor and click events. These positions and events are used to manipulate the navigation system. In an experimental setup the reachable accuracy with the new mouse system is shown.


Effects of liquid digestate on the valence state of vanadium in plant and soil and microbial community response.
Liquid digestate containing high levels of nutrients and humic and fatty acids can affect vanadium species and their plant uptake. To elucidate the effects of liquid digestate on the valence state of vanadium in soil and plant tissue, as well as its effects on the microbial community and soil properties, we grew green bristlegrass (Setaria viridis), a native plant capable of growing in vanadium mining areas, in vanadium-contaminated soils sampled from a mining area and treated it with 5% and 10% liquid digestate for 90 d, respectively. Changes in the concentrations of pentavalent (V[V]) and tetravalent (V[IV]) vanadium in the soils and the shoots and roots of bristlegrass and the soil microbial abundance were measured. The results showed that vanadium existed mainly in the form of V(IV) in the soil but accumulated mainly in the form of V(V) in the bristlegrass. Liquid digestate markedly reduced V(V) concentrations in the soils (by up to 45%) and in the shoots and roots of green bristlegrass (by up to 98%). Liquid digestate enhanced the abundance of Bacteroidetes, which can reduce V(V) to lower valence state. Microbial reduction and phosphorus immobilization were responsible for downregulating V(V) concentrations in the plant and soil. The liquid digestate can be used to enhance in situ bioremediation of vanadium-contaminated soil in mining area.


Nasopharyngeal carcinoma in Taiwan. Clinical manifestations and results of therapy.
A retrospective study was performed on 966 patients with histologically verified nasopharyngeal carcinomas. The follow-up rate was 93.6% over a minimum period of five years. The actuarial and relapse-free survivals were 82% and 49% at one year, 64% and 43% at two years, 43% and 33% at five years, and 36% and 22% at ten years, respectively. None of the patients with distant metastases when initially evaluated survived more than four years following the initiation of radiotherapy and chemotherapy. After the initial radiotherapy was completed, 200 (22.2%) of 900 patients had distant metastases, bone metastases being the most frequent; and 226 (25.1%) patients had locoregional recurrence. There is no statistical correlation found between locoregional recurrence and distant metastases. In patients without recurrence, the rate of subsequent distant metastases is found to be much more heavily influenced by the initial N stage (trend X2 P less than 0.001) than the initial T-stage (trend X2 0.05 greater than P greater than 0.02). Of patients with metastases, the survival time of those with liver metastases was found to be the shortest, 5.4 +/- 0.5 months (mean +/- SEM). Since three quarters of both distant metastases and recurrence developed within two years of the initial radiotherapy, it is highly recommended for patients to be examined monthly during this period. Aggressive retreatment may lead to palliation should recurrence and/or distant metastases be found. Adjuvant chemotherapy is recommended to the patients with T4, N2 or N3 disease following completion of the initial radiotherapy.


Design and synthesis of 6-arylpyridine-tethered sulfonamides as novel selective inhibitors of carbonic anhydrase IX with promising antitumor features toward the human colorectal cancer.
Hypoxia, a characteristic feature of solid tumors, develops as a result of excessive cell proliferation and rapid tumor growth exceeding the oxygen supply, and can result in angiogenesis activation, increased invasiveness, aggressiveness, and metastasis, leading to improved tumor survival and suppression of anticancer drug therapeutic impact. SLC-0111, a ureido benzenesulfonamide, is a selective human carbonic anhydrase (hCA) IX inhibitor in clinical trials for the treatment of hypoxic malignancies. Herein, we describe the design and synthesis of novel 6-arylpyridines 8a-l and 9a-d as structural analogues of SLC-0111, in the aim of exploring new selective inhibitors for the cancer-associated hCA IX isoform. The para-fluorophenyl tail in SLC-0111 was replaced by the privileged 6-arylpyridine motif. Moreover, both ortho- and meta-sulfonamide regioisomers, as well as an ethylene extended analogous were developed. All 6-arylpyridine-based SLC-0111 analogues were screened in vitro for their inhibitory potential against a panel of hCAs (hCA I, II, IV and IX isoforms) using stopped-flow CO2 hydrase assay. In addition, the anticancer activity was firstly explored against a panel of 57 cancer cell lines at the USA NCI-Developmental Therapeutic Program. Compound 8g emerged as the best anti-proliferative candidate with mean GI% value equals 44. Accordingly, a cell viability assay (MTS) for 8g was applied on colorectal HCT-116 and HT-29 cancer cell lines as well as on the healthy HUVEC cells. Thereafter, Annexin V-FITC apoptosis detection, cell cycle, TUNEL, and qRT-PCR, colony formation, and wound healing assays were applied to gain mechanistic insights and to understand the behavior of colorectal cancer cells upon the treatment of compound 8g. Also, a molecular docking analysis was conducted to provide in silico insights into the reported hCA IX inhibitory activity and selectivity.


[Use of anal dilators in the conservative therapy of anal rhagades].
The AA. refer their results in the treatment of anal fissure, using surgical and conservative methods. In their experience, internal lateral sphincterotomy, according to the literature, is the best treatment. The use of anal dilators is effective, but it always needs the patient's compliance.


6-Hydroxydopamine lesions of the ventral tegmentum abolish D-amphetamine and morphine analgesia in the formalin test but not in the tail flick test.
The effect of bilateral 6-hydroxdopamine (with desipramine) lesions of the ventral tegmental area-substantia nigra region on analgesia produced by morphine and D-amphetamine was examined with the formalin and tail flick tests in rats. These lesions depleted dopamine, but not noradrenaline, in the ventral and anterior striatum. Morphine and D-amphetamine produced analgesia in the formalin test in sham lesioned rats but not in lesioned rats. In contrast, morphine produced the same degree of analgesia in the tail flick test in sham lesioned and lesioned rats while D-amphetamine did not produce analgesia in this test. These data suggest that morphine and D-amphetamine analgesia in the formalin test involves dopamine, whereas morphine analgesia in the tail flick test does not.


A mouse hepatocyte carbohydrate-specific receptor and its interaction with liver-metastasizing tumor cells.
Spontaneous high-metastatic variants (ESb) of the DBA/2 mouse lymphoma L5178Y which show heavy liver involvement were found to form rosettes in vitro with isolated autologous hepatocytes, whilst low-metastatic sublines of the same tumor (Eb) did not. An analysis of the molecules involved in the hepatocyte:tumor cell interaction was performed by affinity adsorption and SDS-polyacrylamide gel electrophoresis of 125I-labelled membrane components from either the hepatocytes or the tumor cells. The hepatocytes were found to bind ESb tumor cells through lectin-like hepatic binding proteins (HBP) with molecular weights of 52, 56 and 110 Kd and specificity for D-galactosyl and N-acetyl-D-galactosaminyl residues. More than 10 different cell surface glycoproteins of ESb tumor cells and none of Eb-type tumor cells served as ligands in the hepatocyte interaction. The low-metastatic subline Eb formed hepatocyte rosettes only after neuraminidase pretreatment, indicating that lectin binding carbohydrate structures existed in a cryptic form masked on these cells by sialic acid. Although lectin-carbohydrate interactions have been found to play a crucial role in many intercellular recognition processes, this apparently is the first molecular description of such an interaction between organ-derived normal parenchymal cells and tumor cells. The possible relevance of such an interaction for cancer metastasis is suggested by the finding that spleen-selected ESb sublines differed from liver-selected ones in their organotropism as well as in their ability to form hepatocyte rosettes.


Exploratory EEG data analysis for psychophysiological experiments.
A method for the exploratory analysis of electroencephalographic (EEG) data for neurophysiological experiments is presented. It is based on a time-frequency decomposition of the EEG time series, which is measured by several electrodes in the scalp surface, and includes the computation of a statistic that measures the deviations of the log-power with respect to the pre-stimulus average; the computation of a significance index for these deviations; a new type of display (the time-frequency-topography plot) for the visualization of these indices, and the segmentation of the time-frequency plane into regions with uniform activation patterns. As a particular example, an experiment to study EEG changes during figure and word categorization is analyzed in detail.


Clinical Application of High-frequency Ultrasound in Treatment of Infantile Hemangiomas.
To study the clinical application of high-frequency ultrasound in the treatment of infantile hemangiomas. Ultrasonographic data before and after treatment for 1 month, 3 months and 5 months were recorded from 80 patients with infantile hemangioma. The hemangioma was monitored dynamically with relevant indexes before and after treatment, and the treatment results were divided into 2 groups: the treatment-effective group of 70 cases and the treatment-ineffective group of 10 cases. The differences of tumor size, internal echo and hemodynamic parameters (peak arterial systolic flow velocity, resistance index and venous velocity) were compared before and after treatment, and reliable ultrasound observation indexes were summarized. After treatment, in the treatment-effective group, the thickness of tumor was reduced in all cases, the blood flow signals decreased in 55 cases, the peak systolic velocity decreased in 55 cases, resistance index increased in 55 cases, and venous flow velocity decreased in 53 cases; the differences were statistically significant compared with those before treatment (P < 0.05). The thickness of tumors was significantly decreased after 5 months of treatment compared with 1 month and 2 month treatment (P < 0.05). There was no significant difference in the longitudinal and transverse diameter of tumors after treatment (P > 0.05). In the treatment-ineffective group, there was no significant difference in the above indexes before and after treatment (P > 0.05). High-frequency ultrasound had primary application value in the treatment of infantile hemangiomas, where the change of tumor thickness provided the most important observational indicator.


Transgenic rice plants expressing a fused protein of Cry1Ab/Vip3H has resistance to rice stem borers under laboratory and field conditions.
Six transgenic rice, Oryza sativa L., lines (G6H1, G6H2, G6H3, G6H4, G6H5, and G6H6) expressing a fused Cry1Ab/Vip3H protein, were evaluated for resistance against the Asiatic rice borer, Chilo suppressalis (Walker) (Lepidoptera: Crambidae), and the stem borer Sesamia inferens (Walker) (Lepidoptera: Noctuidae) in the laboratory and field. The bioassay results indicated that the mortality of Asiatic rice borer and S. inferens neonate larvae on six transgenic lines from seedling to filling stage was up to 100% at 168 h after infestation. The cumulative feeding area by Asiatic rice borer neonate larvae on all transgenic lines was significantly reduced compared with the untransformed parental 'Xiushui 110' rice. A 2-yr field evaluation showed that damage during the vegetative stage (deadheart) or during the reproductive stage (whitehead) caused by Asiatic rice borer and S. inferens for transgenic lines was much lower than the control. For three lines (G6H1, G6H2, and G6H6), no damage was found during the entire growing period. Estimation of fused Cry1Ab/Vip3H protein concentrations using PathoScreen kit for Bt-Cry1Ab/1Ac protein indicated that the expression levels of Cry1Ab protein both in main stems (within the average range of 0.006-0.073% of total soluble protein) and their flag leaves (within the average range of 0.001-0.038% of total soluble protein) were significantly different among six transgenic lines at different developmental stages. Both laboratory and field researches suggested that the transgenic rice lines have considerable potential for protecting rice from attack by both stem borers.


Contraception with subdermal levonorgestrel implants as an alternative to surgical contraception at Ilorin, Nigeria.
Acceptability and social characteristics of a cohort of Norplant, IUD, pill and depo-med-roxyprogesterone acetate (DMPA) acceptors who were seen at the University of Ilorin Family Planning Clinic over a 10-week period of the pre-introductory clinical trial of Norplant, are compared. Findings indicate that Norplant and DMPA are adopted as an alternative to sterilization by women advanced in reproductive age and of high parity. The pill and IUD are adopted mainly as birth-spacing methods. Women's education, but not previous use of a contraceptive method, influenced the adoption of Norplant. The continuation rate at 12 months, a measure of acceptability, was highest, 93.7 per 100 women, for Norplant and 77.9, 46.7 and 27.7 per 100 women for the IUD, DMPA and the pill, respectively. The need to address the high family size norms in the African subregion is discussed.


Child and adolescent victims in forensic autopsy: a 5-year retrospective study.
Children of more than 3 years of age and adolescents have been largely overlooked in the forensic literature, especially the 4-9 age group. Thus, the present study was undertaken to address this particular issue of child and adolescent victims in forensic autopsies. On a 5-year period (2000-2004) in Quebec province (Canada), all forensic autopsy cases of children and adolescents from 4 to 19 years of age were retrospectively studied. A total of 223 cases of child and adolescent deaths (148 males, 75 females; 6.6% of all forensic autopsies) were reviewed. Age, gender, manner of death and cause of death were analyzed for all victims organized into three groups of age: 4-9, 10-14, and 15-19. Moreover, homicide cases (n = 54) are further analyzed in terms of method(s) used (firearm, sharp force, asphyxia, blunt force, intoxication). This 5-year retrospective study may contribute to a better understanding of typical deaths in the 4-19 group of age and therefore, bring a working basis for the forensic pathologist or medical examiner/coroner.


Multimodal analysis of the biomechanical impact of knee angle on the Sit-to-Stand transition.
The Sit-to-Stand (STS) transition is one of the most used activities of daily living and vital for independence. Neurological, or physical injuries impairing functional mobility or sensory feedback often require rehabilitative programs or therapeutic interventions. Understanding the biomechanical elements of daily movements and the interaction between these elements may help inform rehabilitation protocols and optimize targeted interventions, such as stimulation protocols. What are the effects of different initial knee angle, arm facilitation and proprioceptive input on leg muscle activation patterns and balance during and after a sit-to-stand? EMG of four lower limb muscles were recorded in 20 healthy participants as well centre-of-pressure sway amplitude and velocity, as participants stood from a seated position. Initial knee angles were set to various levels of extension (80°, 90°, 100°) and surface stability and arm facilitation were altered using a foam mat or crossing arms. Data were analysed across 3 phases of the STS transition. More extended knee angles resulted in greater mediolateral sway during each phase (p < .01) and had a detrimental effect on anterior-posterior sway in phases 1 and 3. EMG data suggested more extended initial knee angles also increased EMG activity of the Tibialis Anterior (p < .001) and Bicep Femoris (p < .02) within Phases 1 and 2 to assist lift and stabilisation. Findings of this study outline phase-based muscle involvement as well as the compounding effects of reduced proprioceptive input and knee angle, on difficulty of the STS transition. Such results emphasising the need to take sensory and mobility issues into consideration when designing rehabilitative programs or stimulation control systems.


Prostate Cancer: Update on Grading and Reporting.
The Gleason scoring system and Grade Group systems facilitate accurate grading and reporting of prostate cancer, which are essential tasks for surgical pathologists. Gleason Pattern 4 is critical to recognize because it signifies a risk for more aggressive behavior than Gleason Pattern 3 carcinoma. Prostatic adenocarcinoma with radiation or androgen therapy effect, with aberrant P63 expression, or with Paneth cell-like differentiation represent pitfalls in prostate cancer grading because although they display architecture associated with aggressive behavior in usual prostatic adenocarcinoma, they do not behave aggressively and using conventional Gleason scoring in these tumors would significantly overstate their biologic potential.


Alterations of N-3 polyunsaturated fatty acid-activated K2P channels in hypoxia-induced pulmonary hypertension.
Polyunsaturated fatty acid (PUFA)-activated two-pore domain potassium channels (K2P ) have been proposed to be expressed in the pulmonary vasculature. However, their physiological or pathophysiological roles are poorly defined. Here, we tested the hypothesis that PUFA-activated K2P are involved in pulmonary vasorelaxation and that alterations of channel expression are pathophysiologically linked to pulmonary hypertension. Expression of PUFA-activated K2P in the murine lung was investigated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), by patch clamp (PC) and myography. K2P -gene expression was examined in chronic hypoxic mice. qRT-PCR showed that the K2P 2.1 and K2P 6.1 were the predominantly expressed K2P in the murine lung. IHC revealed protein expression of K2P 2.1 and K2P 6.1 in the endothelium of pulmonary arteries and of K2P 6.1 in bronchial epithelium. PC showed pimozide-sensitive K2P -like K(+) -current activated by docosahexaenoic acid (DHA) in freshly isolated endothelial cells as well as DHA-induced membrane hyperpolarization. Myography on pulmonary arteries showed that DHA induced concentration-dependent instantaneous relaxations that were resistant to endothelial removal and inhibition of NO and prostacyclin synthesis and to a cocktail of blockers of calcium-activated K(+) channels but were abolished by high extracellular (30 mM) K(+) -concentration. Gene expression and protein of K2P 2.1 were not altered in chronic hypoxic mice, while K2P 6.1 was up-regulated by fourfold. In conclusion, the PUFA-activated K2P 2.1 and K2P 6.1 are expressed in murine lung and functional K2P -like channels contribute to endothelium hyperpolarization and pulmonary artery relaxation. The increased K2P 6.1-gene expression may represent a novel counter-regulatory mechanism in pulmonary hypertension and suggest that arterial K2P 2.1 and K2P 6.1 could be novel therapeutic targets.


Sensitivity-enhanced multiple-quantum MAS NMR for half-integer spin quadrupolar nuclei using WURST-amplitude shaped pulses.
Two-dimensional multiple-quantum MAS (MQMAS) NMR spectroscopy is one of the most widely used solid-state NMR techniques for resolving multiple overlapping central-transition lineshapes for half-integer spin quadrupolar nuclei. In particular when relying on nutation-driven MQ coherence transfers, this technique suffers from low sensitivity that can only be improved by increasing the rf-amplitude of the involved radio-frequency (rf) pulses, which are therefore typically operated at the rf-limit. In such situations, frequently encountered for the three-pulse z-filtered and split-t1 shifted-echo MQMAS NMR sequences, we introduce the advantages of rf-pulses with smoothly truncated amplitude profiles, which we have termed WURST-Amplitude Shaped Pulses (WASPs). When considering the NMR spectrometer hardware, we demonstrate that WASPs feature more suitable properties in comparison to conventional rectangular pulses, enabling a substantial reduction of voltage reflections and transient effects under identical rf-conditions. By employing extensive numerical simulations and experimental validation, we further show that WASPs intrinsically possess a higher potential for nutation-based 3Q excitation involving spin-3/2 and 3Q and 5Q excitation for spin-5/2 quadrupolar nuclei, specifically when large nutation frequencies are available. The concept of smoothly truncating rf-amplitudes is also extended to Fast Amplitude Modulation (FAM) pulses, normally incorporated for rotor-driven 1Q conversion. We additionally evaluate the potential of employing WASPs with peak rf-amplitudes beyond the rf-limit for conventional rectangular rf-pulses.


Synthesis and characterization of acrylic type hydrogels containing azo derivatives of 5-amino salicylic acid for colon-specific drug delivery.
pH-sensitive hydrogels are suitable candidates for oral delivery of therapeutic peptides, proteins and drugs, due to their ability to respond to environmental pH changes. Terephthalic acid was covalently linked with 2-hydroxyethyl methacrylate (HEMA), abbreviated as cross-linking agent (CA). Acryloyl ester of 5-[4-(hydroxy phenyl) azo] salicylic acid (HPAS) as an azo derivative of 5-amino salicylic acid (5-ASA) was prepared under mild conditions. The HPAS was covalently linked with acryloyl chloride, abbreviated as APAS. Free radical cross-linking copolymerization of polymerizable azo derivative of 5-ASA (APAS) and methacrylic acid (MAA) in two different molar ratios, with the various ratios CA as cross-linking agent were carried out with using 2, 2'-azobisisobutyronitrile (AIBN) as initiator at the temperature range 60-70 degrees C. The composition of the cross-linked three-dimensional polymers was determined by FTIR spectroscopy. Glass transition temperature (Tg) of the network polymers was determined calorimetrically. The hydrolysis of drug-polymer conjugates was carried out in cellophane membrane dialysis bags containing aqueous buffer solutions (pH 7.4 and pH 1) at 37 degrees C. The effect of copolymer composition on the hydrolytic degradation was studied in simulated gastric fluid (SGF, pH 1) and simulated intestinal fluid (SIF, pH 7.4) at 37 degrees C. Monitoring of the hydrolysis process by HPLC and UV spectroscopy shows that the azo prodrug (HPAS) was released by hydrolysis of the ester bond located between the HPAS and the polymer chain. The drug-release profiles indicate that amount drug release dependent on the content of MAA groups and crosslinking.


Changes in S100A8/A9 and S100A12 and Their Comparison with Other Analytes in the Saliva of Pigs with Diarrhea Due to E. coli.
The family of calgranulins includes S100A8 (calgranulin A), S100A9 (calgranulin B), which can appear as a heterodimer known as S100A8/A9 or calprotectin, and S100A12 (calgranulin C). These proteins are related to different inflammatory conditions, immune-mediated diseases, and sepsis and are considered biomarkers of potential interest. This study aims to evaluate if S100A8/A9 and A12 could change in pigs with diarrhea due to E. coli and to compare the changes of S100A8/A9 and A12 with other analytes in order to explore the possible causes or mechanisms involved. For this purpose, a panel integrated by analytes related to inflammation (haptoglobin, inter-alpha trypsin inhibitor 4 (ITIH4), and total protein); immune system (adenosine deaminase, ADA); stress (alpha-amylase); tissue damage (lactate and lactate dehydrogenase (LDH)); sepsis (aldolase) and redox status (ferric-reducing ability of saliva (FRAS) and advanced oxidation protein products (AOPP)) was evaluated. S100A8/A9 and A12 and the other analytes measured in this study showed increases in the saliva of pigs with diarrhea due to E. coli. S100A8/A9 and/or A12 showed a significant correlation of different magnitude with some of the other analytes evaluated. Further studies should be conducted to gain knowledge about the possible practical applications as biomarkers of the measurements of S100A8/A9 and A12 in the saliva of pigs.


Blood-brain barrier taurine transport during osmotic stress and in focal cerebral ischemia.
Little is known about blood to brain taurine transport despite substantial evidence suggesting a role of taurine in brain volume regulation during osmotic stress or conditions inducing cell swelling, such as ischemia. We have made measurements of the taurine influx rate constant (K1) with [3H]taurine in three conditions: raised plasma taurine concentrations induced by infusion with 50 mM taurine (10 microliters/100 g/min); osmotic stress induced by i.p. injections of 1.5 M NaCl (2 ml/100 g) or distilled water (10 ml/100 g); and 4 h of middle cerebral artery occlusion (MCAo). In rats with MCAo, additional determinations were made of tissue water and taurine contents, and blood-brain barrier passive permeability with [3H]alpha-aminoisobutyric acid. Taurine infusion increased plasma taurine from 110 +/- 63 microM (SD) to 407 +/- 63 (p < 0.001) and decreased taurine K1 at the blood-brain barrier by 70% (p < 0.001), signifying saturable uptake that maintained unidirectional influx constant. Similarly, although hypo- and hyperosmolality increased and decreased plasma taurine concentration, respectively, a reciprocal relationship between K1 and plasma taurine in these experiments ensured that unidirectional fluxes of taurine into brain were unchanged by osmotic stress. During MCAo, the taurine K1 was reduced 80% in the ipsilateral ischemic tissue compared with the contralateral nonischemic tissue (p < 0.001). This decline may be due to a release of taurine into the brain circulation, because there was a concomitant loss of tissue taurine of 7.4 +/- 2.4 mmol/g dry weight (p < 0.05). Alternately, if taurine uptake is sodium dependent, the decline might reflect a disruption of the endothelial sodium gradient.


Bone phenotype of the aromatase deficient mouse.
Estrogens are important for normal bone growth and metabolism. The mechanisms are incompletely understood. Thus, we have undertaken characterization of the skeletal phenotype of aromatase (ArKO) deficient mice. No abnormalities have been noted in skeletal patterning in newborns. Adult ArKO mice show decreased femur length and decreased peak Bone Mineral Density (BMD) with accelerated bone loss by 7 months of age in females. Magnetic resonance microscopy (MR) and microCT (microCT) imaging disclosed decreased cancellous connectivity and reduced cancellous bone volume in ArKO females. Bone formation rate (BFR) is increased in ArKO females and decreased in ArKO males. Estradiol therapy reverses these changes. This anabolic effect of estradiol in the male skeleton is supported by 18-F- Positron Emission Tomography (PET) imaging, which clearly demonstrates decreased spinal uptake, but marked increase after estradiol therapy. Serum IGF-1 levels are high in young female ArKO mice but low in young ArKO males. The reduced BMD in ArKO females, despite the presence of elevated serum IGF 1, suggests that other mechanism(s) are operative. There is increased B-cell lymphopoiesis in adult female ArKO bone marrow cells. These results show that ArKO mice show the effects of estrogen deficiency on bone growth, mass, metabolism, microarchitecture and the hematopoietic microenvironment.


The effect of inorganic salt type and concentration on hydrophilic drug loading into microspheres using the emulsion/solvent diffusion method.
In order to avoid gastric irritation caused by tolmetin sodium (TS), gastro resistant Eudragit® S 100 microsphere formulations were prepared with the emulsion/solvent diffusion method. Considering the high water solubility of the TS molecule, the effects of the presence of inorganic salt (NaCl, NaBr and KH2PO4; 0.1 M and 1.0 M) in external phase and external phase pH on the encapsulation efficiency were evaluated. Percentage yield value was found to vary between 55.8% and 72.1%. Improvement in encapsulation efficiency was determined by increasing concentrations of NaCl, NaBr and KH2PO4. The microspheres were observed to have a spherical shape and the measured particle size values varied between 52.1 and 81.5 µm. The released amounts of the drug were found to be low as the inorganic salt concentrations increased. Conclusively, drug release in stomach pH was significantly prevented by the microspheres prepared using Eudragit® S 100 polymer, and these formulations are considered to be a model for other orally administered drugs with similar problems.


Effectiveness of a UVC air disinfection system for the HVAC of an ICU.
Ultraviolet germicidal irradiation (UVGI) uses short-wave ultraviolet (UVC) light to inactivate organisms like viruses, bacteria, and fungi. UVC inactivates a wide range of microorganisms by damaging the structure of nucleic acids and proteins at the molecular level, so they become unable to replicate and cause disease. Thus, UVC can improve indoor air quality by controlling bioaerosols and can be used as an engineering device to interrupt the transmission of pathogenic organisms and potential bioterrorism agents. Recently, the World Health Organization recognized that the COVID-19 virus could be transmitted across large distances, suggesting that indoor ventilation is key in airborne transmission. As a test for the future dissemination of UVC light installations to improve indoor air quality in Hospitals in Sergipe State, Brazil, we made a first installation of UVGI disinfection lamps, strategically placed in the Heating, Ventilating, and Air Conditioning (HVAC) system of the Intensive Care Unit (ICU) at the University Hospital of Lagarto, Federal University of Sergipe, Brazil. Six 15 W low-vapor-pressure mercury lamps emitting 253.7 nm UVGI were installed in the ducts of the fan coil, maximizing their luminous interaction in the air passage. One of the greatest advantages of this type of installation is that the lamps were completely covered, avoiding any risk of hazardous exposure to people and animals. Microbiological tests were carried out to verify the germicidal effect, analyzing the viability of microorganisms circulating in the environment. In this paper, we present our encouraging results, demonstrating the effectiveness of the installation, suggesting that similar devices should be installed in HVAC systems to avoid biological risk to people inside buildings. In addition, we believe that this study may provide useful evidence and guidance for the design of equipment intended to abate the microorganisms that may be used in CBRNE terror attacks.


[Immunotherapy and its possible application in malignomas of the orofacial region. Review].
The authors give an account of the types of active and passive immunotherapy in malignomas. Based on data in the literature they evaluate its possibilities in clinically used and perspective methods. For practical use in the orofacial region they emphasize the necessity to follow up tumour markers.


Triaging and referring in adjacent general and emergency departments (the TRIAGE trial): A cluster randomised controlled trial.
To determine whether a new triage system safely diverts a proportion of emergency department (ED) patients to a general practitioner cooperative (GPC). Unblinded randomised controlled trial with weekends serving as clusters (three intervention clusters for each control). The intervention was triage by a nurse using a new extension to the Manchester Triage System assigning low-risk patients to the GPC. During intervention weekends, patients were encouraged to follow this assignment; it was not communicated during control weekends (all patients remained at the ED). The primary outcome was the proportion of patients assigned to and handled by the GPC during intervention weekends. The trial was randomised for the secondary outcome: the proportion of patients assigned to the GPC. Additional outcomes were association of these outcomes with possible confounders (study tool parameters, nurse, and patient characteristics), proportion of patients referred back to the ED by the GPC, hospitalisations, and performance of the study tool to detect primary care patients (the opinion of the treating physician was the gold standard). In the intervention group, 838/6294 patients (13.3%, 95% CI 12.5 to 14.2) were assigned to the GPC, in the control group this was 431/1744 (24.7%, 95% CI 22.7 to 26.8). In total, 599/6294 patients (9.5%, 95% CI 8.8 to 10.3) experienced the primary outcome which was influenced by the reason for encounter, age, and the nurse. 24/599 patients (4.0%, 95% CI 2.7 to 5.9) were referred back to the ED, three were hospitalised. Positive and negative predictive values of the studied tool during intervention weekends were 0.96 (95%CI 0.94 to 0.97) and 0.60 (95% CI 0.58 to 0.62). Out of the patients assigned to the GPC, 2.4% (95% CI 1.7 to 3.4) were hospitalised. ED nurses using a new tool safely diverted 9.5% of the included patients to primary care. ClinicalTrials.gov Identifier: NCT03793972.


Antibiotics for the eradication of Propionibacterium acnes biofilms in surgical infection.
Propionibacterium acnes is increasingly recognized as a cause of delayed infection after spinal instrumentation or shunting for hydrocephalus. Biofilm development by this organism has recently been demonstrated. We therefore investigated the effect of two different courses of three antibiotics (penicillin, rifampicin and linezolid) on mature P. acnes biofilms in vitro. Outcomes were eradication or regrowth after withdrawal of antibiotics, simulating successful treatment and relapse. P. acnes biofilms were grown on titanium discs for 6 days until mature, then exposed to the antibiotics for either 7 or 14 days before sonication and culture. Further, discs were similarly exposed, but after each course, they were reincubated for a further 9 days to check for regrowth. Penicillin, linezolid and linezolid plus rifampicin eradicated P. acnes biofilms after 14 days, but only penicillin had this effect after 7 days. 'Relapse' was prevented only by 14 day courses of penicillin or linezolid plus rifampicin, but not by linezolid alone. For P. acnes spinal instrumentation infections, either penicillin or linezolid plus rifampicin might be equally effective. For shunt infections, as penicillin does not give therapeutic cerebrospinal fluid concentrations, rifampicin plus linezolid might be the treatment of choice. Linezolid alone appears not to be as effective as penicillin against P. acnes biofilms.


Lepromatous leprosy patients show T helper 1-like cytokine profile with differential expression of interleukin-10 during type 1 and 2 reactions.
Some leprosy patients suffer from clinical episodes associated with tissue damage which are designated as Type 1 (reversal reaction) when localized to the lesions and Type 2 (erythema nodosum leprosum, ENL) when accompanied by systemic involvement. We had reported earlier that stable, non-reaction lepromatous leprosy subjects show T helper 2 (Th2)- and Th0- but not Th1-like responses in the peripheral blood. To further understand the development of Th-like responses during disease, 32 lepromatous patients undergoing reactions were studied using cytokine-specific reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) in peripheral blood and some skin biopsies. Of interest was the evidence of a Th1-like response with presence of interferon-gamma (IFN-gamma) and absence of interleukin-4 (IL-4) mRNA in the peripheral blood mononuclear cells (PBMC) of 85 and 64% of Type 1 and 2 reaction patients, respectively, and in all reaction sites. Whereas a Th0- was seen in some, a Th2-like response was absent. IL-12p40 mRNA was seen in 21/25 ENL and all Type 1 reaction subjects irrespective of the Th phenotype. IL-12p40 and IFN-gamma were detectable in unstimulated PBMC suggesting an in vivo priming during reactions. IL-10 was mainly associated with adherent cells and showed a differential expression in the two reactions. It was present in the PBMC of ENL but not in reversal reaction patients. Moreover, it was not detectable in the skin lesions of either type of reactions. A Th1-like cytokine profile was associated with immunopathology and persisted up to 6-7 months after the onset of reactions.


lncRNA GAS5 suppresses rheumatoid arthritis by inhibiting miR-361-5p and increasing PDK4.
Rheumatoid arthritis (RA) is an inflammatory disease that causes hyperplasia of synovial tissue and cartilage destruction. This research was to investigate the effects of lncRNA GAS5/miR-361-5p/PDK4 on rheumatoid arthritis. By qRT-PCR, GAS5 and PDK4 were found to be overexpressed in synovial tissue, fibroblast-like synoviocytes of RA patients and LPS-induced chondrocytes, while the miR-361-5p expression was significantly reduced. GAS5 overexpression resulted in a decrease in the proliferation and Bcl-2 protein expression, and an increase in the Bax protein level. On the contrary, miR-361-5p sponged by GAS5 could accelerate chondrocyte proliferation, inhibit apoptosis. PDK4 targeted by miR-361-5p could inhibit RA, and partially eliminated the effect of miR-361-5p on RA. Our study suggested that GAS5 suppressed RA by competitively adsorbing miR-361-5p to modulate PDK4 expression.


Coptisine exert cardioprotective effect through anti-oxidative and inhibition of RhoA/Rho kinase pathway on isoproterenol-induced myocardial infarction in rats.
Because myocardial infarction is a major cause of morbidity and mortality worldwide, protecting the heart from the ischemia is the focus of intense research. Coptisine is an isoquinoline alkaloid extracted form Coptidis Rhizoma. This study aims to elucidate if coptisine is responsible for cardioprotection using myocardial infarction (MI) rat models and investigate its potential mechanism of action. Myocardial infarction was produced in rats with 85 mgkg(-1) isoproterenol administered subcutaneously twice at an interval of 24 h. The rats were randomized into 7 groups: (I) Normal; (II) ISO; (III) ISO+fasudil; (IV) ISO+isosorbide dinitrate (ISDN) and (V-VII) ISO+coptisine (25, 50 and 100 mgkg(-1)). Cardiac function and markers of cardiac ischemic were assessed after MI. Rats pretreated with coptisine (25, 50 and 100 mgkg(-1)) for 21 days and received subcutaneously injected with ISO (85 mgkg(-1)) on the 20th and 21st day at an interval of 24 h. The results suggested that coptisine has strong antioxidant activity, and it can maintain cell membrane integrity, ameliorate mitochondrial respiratory dysfunction, reduce myocardial cells apoptosis, inhibit RhoA/ROCK expression induced by high-dose isoproterenol administration. Coptisine provided cardioprotection in a model of myocardial infarction, and therefore should be considered as a novel adjunctive therapy for attenuating myocardial damage.


Anabolic-androgenic steroid use in a young body-builder: A case report and review of the literature.
Anabolic-androgenic steroid (AAS) abuse is routine in athletes to enhance their overall physique. It often leads to detrimental effects, including cardiovascular diseases, hormonal imbalances, and cancer. Our case presentation emphasizes two important aspects: the first is the importance of thorough history taking in correctly diagnosing diseases with multiple etiologies. The second one relates to the reversible and preventable hazards of the increasing incidence of usage of illicit drugs, mainly androgenic anabolic steroids in young adults. We present a case of a 30-year-old male bodybuilder with presenting complaints of increased anxiousness, excessive anger, and dyspnea on minimal exertion. Echocardiogram showed a dilated cardiomyopathy with left ventricular ejection fraction (LVEF) of 20%. The patient was counseled for quitting AAS and symptomatically treated on heart failure management guidelines. He responded well to the management plan and now enjoying a healthy life. It is imperative to raise awareness regarding the substantial adverse effects of AAS abuse that might precipitate severe cardiovascular system complications leading to morbidity and eventual mortality. Most of the times, the pathological changes due to AAS abuse are reversible. This shows a good prognosis and better compliance with the management plan advised to the patients.


Civil servants' demand for social health insurance in Northwest Ethiopia.
Absence of reliable health insurance schemes is a key challenge to meet the universal health coverage target of the Sustainable Development Goals (SDGs). Ethiopian health system is characterized by under financing, low protection mechanisms for the poor, and lack of mechanisms of risk pooling and cost sharing. Ethiopia is implementing social health insurance (SHI) scheme to reduce out of pocket payment (OOP) and improve access and use of healthcare. This study aimed to determine the demand for SHI among civil servants and associated factors in Northwest Ethiopia. An institution-based cross-sectional study was conducted in Bahir Dar city from 557 randomly selected civil servants using structured and self-administered questionaire. The questionnaire included questions measuring demand for SHI and demographic, socio-economic, healthcare related and personal and behavioral factors. Data were first entered in Epi-Info version 7.0 and transferred to SPSS version 20 for analysis. Descriptive statistics, bivariate and multivariable logistic regression analysis were performed. From the total calculated sample size of 557, 488 respondents returned the questionnaire giving a response rate of 88%. Nearly three-fourth of the respondents, 355 (72.7%), reported their need to be enrolled in a SHI scheme. Two-third of the respondents 325 (66.6%) were willing to pay for their enrollment. Overall, three hundred and two (61.9%) were demanding SHI. Having good awareness about health insurance [AOR = 4.39, 95% CI = (1.82-12.89)] and trust on a health insurance agency [AOR = 3.0, 95% CI = (1.57-5.72)], were significantly associated with the demand for SHI among civil servants. The demand for SHI among civil servants were higher. The awareness towards SHI and trust on the SHI agency were significantly associated with demand for SHI. As Ethiopia aspires to insure all employees of the formal sector, and improving the awareness of civil servants about SHI and the agency providing the service could improve demand for SHI. Further research is important on healthcare organizational and professional readiness to handle the upcoming insurance driven quality health service need and health seeking behavioral change.


[Discuss on evidence for the edition division of Zhenglei Bencao-including the belongings of Shaoxing Bencao and Xinbian Leiyao Tuzhu Bencao].
Before discussion of the editions of Zhenglei Bencao, the relation between the book and its circulating editions (including the features of those editions) should be investigated. Those circulating editions should include preface and materia medica systematics. Their contents should include the text and figures from Bencao Tujing, text from Jiayou Bencao and contents added by TANG. According to the features above, it was found that Shaoxing Bencao was not the circulating edition of Zhenglei Bencao while Xinbian Leiyao Tuzhu Bencao was.


Economic valuation of setting up a social health enterprise in urban poor-resource setting in Kenya.
The failure of the market and government to provide quality healthcare services have been the motivation to set up social health enterprise. However, the value for money associated with setting up a social health enterprise in sub-Sahara African countries has been relatively unexplored in the literature. The study presents the first empirical estimates of the mean willingness-to-pay (WTP) for setting up a social health enterprise that will simultaneously run a health center and provide health insurance scheme in an urban resource-poor setting and explores whether the benefits outweigh the costs. The contingent valuation method is used to estimate the mean WTP for the health insurance scheme proposed by the social health enterprise in Viwandani slum (Nairobi, Kenya). The survey was conducted between June and July 2018 on 300 households. We find that the feasibility of setting up a social health enterprise could be promising with 97 percent of respondents willing to pay about US$ 2 per person per month for a scheme that would provide quality healthcare services. More importantly, setting up the social health enterprise will yield a positive net profit, and investors could expect US$ 1.11 in benefits for each US$ 1 of costs of investment in setting up the social health enterprise. We, therefore, conclude that this health policy in this urban resource-poor setting could be a viable solution to reach the neglected urban households in the Kenyan slums.


Spinal nerve lesion induces upregulation of neuronal nitric oxide synthase in the spinal cord. An immunohistochemical investigation in the rat.
The possibility nitric oxide (NO) is involved the neurodegenrative mechanisms in the spinal cord following a chronic peripheral nerve lesion was examined using NOS immunohistochemistry. Spinal nerve lesion at L-5 and L-6 level was produced according to the Chung model, a model of neuropathic pain and rats were allowed to survive for 8 weeks. In one group of animals L-NAME was given intraperitoneally (1-2 mg/kg, i.p. daily) for 6 weeks. Sham operated rats, in which the spinal nerve was exposed but not ligated, served as controls. Ligation of spinal nerves in rats resulted in an upregulation of NOS which was most pronounced in the ipsilateral gray matter of the spinal cord compared to the contralateral side. In these rats, ultrastructural investigations showed distorted neurons, membrane disruption and myelin vesiculation. Sham operated rats did not show either NOS upregulation or structural changes in the spinal cord. Pretreatment with L-NAME significantly reduced NOS upregulation and the structural changes in the spinal cord were less pronounced. These observations strongly indicate a putative role of NOS in the pathophysiology of chronic nerve lesion. Our results may provide a new strategy to treat chronic neuropathic pain or to minimise neurodegeneration in the patients suffering from such diseases of the nervous system.


Inhibitor of translational initiation in sea urchin eggs prevents mRNA utilization.
Actively reinitiating cell-free translation systems from sea urchin eggs and embryos have been developed. The extracts retain the overall differences in protein synthetic activity observed in intact eggs and embryos. The effect of combining extracts from eggs and embryos suggests the presence of a dominant inhibitor of translation in the egg. This inhibitor also prevents the initiation of translation in a cell-free system from rabbit reticulocytes. In the reticulocyte system, the egg inhibitor causes the accumulation of 48 S preinitiation complexes, as measured by the accumulation of initiator tRNA and globin mRNA on the small ribosomal subunit. Accumulation of this uncommon intermediate suggests either that the inhibitor prevents the binding of the 60 S ribosomal subunit, or that it prevents migration of the 40 S subunit from the 5' end of mRNA to the first AUG.


Trends and causes of maternal mortality in Kazakhstan.
The aim of this study was to determine trends in the rate and causes of maternal mortality in Kazakhstan. Maternal deaths occurring between 1960 and 1996 in the 19 oblast (administrative regions) of Kazakhstan were documented and analyzed. After an initial phase of decrease in the period 1960-1980, the level of maternal mortality in Kazakhstan has been stable at 70-80 maternal deaths per 100,000 live births. Maternal deaths due to hypertension and abortion complications have not substantially decreased. Over the last 10 years, illegal abortions have accounted for most Kazakh maternal deaths resulting from abortion complications. To reduce the maternal death rate, the Kazakh health authorities and health workers (obstetricians, midwives, health educators) must develop and rapidly implement maternal health and family planning policies.


Activity of Pt(II) and Ru(III) Triazolopyrimidine Complexes Against Parasites of the Genus Leishmania, Trypanosomas and Phytomonas.
The synthesis and characterization of two Pt(II) Complexes with the isomeric ligands 4,5-dihydro-5-oxo- [1,2,4]triazolo-[ 1,5-a]pyrimidine (5HtpO) and 4,7-dihydro-7-oxo-[ 1,2,4]-triazolo-[ 1,5-a]pyrimidine (7HtpO) are described, as well as a Ru(III) complex with 7HtpO. The crystal structure of cis-[PtCl(2)(7HtpO)(2)].2H(2)O has been solved by X-ray diffraction analysis. In vitro activity of the new isolated complexes against the epimastigote form of T. cruzi, procyclic form of T. b. brucei and promastigote form of L. donnovani and P. characias has also been studied. The three complexes markedly affect the growth of the parasites and none of them shows cytotoxicity against macrophage of the J774.2 line at the heaviest dosages used.


Zinc binding in bovine milk.
About 90% of the Zn in bovine skim milk was sedimented by ultracentrifugation at 100,000 g for 1 h. About half of the non-sedimentable Zn was non-dialysable, indicating that it was associated with protein, probably non-sedimented casein micelles. Casein micelles incorporated considerable amounts of Zn added to skim milk as ZnCl2, and at Zn concentrations greater than or equal to 16 mM coagulation of casein micelles occurred. Ca was displaced from casein micelles by increasing ZnCl2 concentration and approximately 40% of micellar Ca was displaced by 16 mM-ZnCl2. Micellar Zn, Ca and Pi were gradually rendered soluble as the pH of milk was lowered and at pH 4.6 greater than 95% of the Zn, Ca and Pi were non-sedimentable. These changes were largely reversible by readjustment of the pH to 6.7. About 40% of the total Zn in skim milk was non-sedimentable at 0.2 mM-EDTA and most of the remainder was gradually rendered soluble by EDTA over the concentration range 1-50 mM. This indicates that there are two distinct micellar Zn fractions. No micellar Ca or Pi was solubilized at EDTA concentrations up to 1.0 mM, indicating that both colloidal calcium phosphate (CCP) and casein micelles remained intact under conditions where the more loosely bound micellar Zn fraction dissolved. Depletion of casein micelles of colloidal Ca and Pi by acidification and equilibrium dialysis resulted in removal of Zn, and in colloidal Pi-free milk non-dialysable Zn was reduced to 1.2 mg/l (approximately 32% of the original Zn). Thus, approximately 32% of the Zn in skim milk is directly bound to caseins, while approximately 63% is associated with CCP. Over 80% of the Zn in colloidal Pi-free milk was rendered soluble by 0.2 mM-EDTA, indicating that the casein-bound Zn is the loosely bound Zn fraction in casein micelles. A considerable fraction of the Zn in acid whey (pH 4.6) co-precipitated with Ca and Pi on raising the pH to 6.7 and heating for 2 h at 40 degrees C, indicating that insoluble Zn phosphate complexes form readily under these conditions. Studies on dialysis of milk against water, or dilution of milk or casein micelles with water, showed that CCP and its associated Zn is very stable and dissolves only very slowly at pH 6.6. The nature of Zn binding in casein micelles may help to explain the lower nutritional bioavailability of Zn in bovine milk and infant formulae compared with human milk.


Skeletal muscle mitochondrial function and exercise capacity in HIV-infected patients with lipodystrophy and elevated p-lactate levels.
To investigate the skeletal muscle mitochondrial function in HIV-infected patients with lipodystrophy or elevated p-lactate levels. Eight HIV patients treated with highly active antiretroviral therapy, with lipodystrophy or elevated p-lactate, and eight healthy controls were exposed to incremental exercise until exhaustion. Blood samples and gas analysis were performed at rest, during exercise and in recovery. Oxygen consumption, workload and blood lactate were assessed. Before and immediately after exercise muscle biopsies were obtained, in which citrate synthase (CS), hydroxyacyl-coenzyme A dehydrogenase (HD), glycogen and nucleotides were measured. Maximal workload was significantly lower in patients compared with controls [171 Watt (88-206) versus 235 Watt (118-294) P = 0.05]. A trend towards lower maximal oxygen consumption (VO(2max)) was detected in patients [2136 ml/min (1221-2598) versus 2985 ml/min (1506-3959) P = 0.11]. Patients had significantly elevated levels of blood lactate at rest [1.55 mmol/l (1-2.5) versus 0.8 mmo/l (0.37-1.1) P < 0.01), but no significant difference in maximal blood-lactate values was found. The decline in blood lactate in the recovery period was similar between groups. There was no significant difference in CS, HD, glycogen or nucleotides. The significantly lower working capacity and the trend towards reduced VO(2max) in patients could be caused by mitochondrial dysfunction, but may also be caused by impaired physical fitness. The similar levels of nucleotides, CS, HD, and glycogen and the normal increase in blood lactate during exercise indicates a normal oxidative phosphorylation. No evidence of serious damage to skeletal muscle mitochondrial function was found.


Myocardial Infarction in the "Young": Risk Factors, Presentation, Management and Prognosis.
Myocardial infarction (MI) in the "young" is a significant problem, however there is scarcity of data on premature coronary heart disease (CHD) and MI in the "young". This may lead to under-appreciation of important differences that exist between "young" MI patients versus an older cohort. Traditional differences described in the risk factor profile of younger MI compared to older patients include a higher prevalence of smoking, family history of premature CHD and male gender. Recently, other potentially important differences have been described. Most "young" MI patients will present with non-ST elevation MI but the proportion presenting with ST-elevation MI is increasing. Coronary angiography usually reveals less extensive disease in "young" MI patients, which has implications for management. Short-term prognosis of "young" MI patients is better than for older patients, however contemporary data raises concerns regarding longer-term outcomes, particularly in those with reduced left ventricular systolic function. Here we review the differences in rate, risk factor profile, presentation, management and prognosis between "young" and older MI patients.


Foley Catheter as a Tourniquet for Hemorrhage Prevention during Peripartum Hysterectomy in Patients with Placenta Accreta Spectrum (PAS)-A Hospital-Based Study.
Placenta accreta spectrum (PAS) is a clinical entity significantly increasing the risk of a peripartum hemorrhage. Various surgical methods have been described in the literature, which aim to reduce the risk of bleeding, although they often lack reproducibility and have been performed on low numbers of patients. The aim of this study was to evaluate the use of the Foley catheter as a cervical tourniquet during cesarean sections, in patients with PAS. All patients who underwent peripartum hysterectomy due to PAS in a large single-center registry were included in the present analysis. The general demographics and clinical characteristics of all participants, including blood loss, and maternal and fetal outcomes, were collected and analyzed. Twelve participants were included. The mean blood loss was 1200 ± 760 ml during operation and the mean ± SD procedural duration was 89 ± 17 min. The median (Q1-Q3) length of hospital stay post-procedurally was 5 (4-6) days. None of the patients required subsequent urgent surgical procedures after hysterectomy. The median (Q1-Q3) packed red blood cell units transfused in our cohort was 2 (0-3). Using the Foley catheter as a tourniquet might be an effective method of excessive bleeding prevention in patients with PAS during peripartum hysterectomy.


Block of CDK1-dependent polyadenosine elongation of Cyclin B mRNA in metaphase-i-arrested starfish oocytes is released by intracellular pH elevation upon spawning.
Meiotic progression requires the translation of maternal mRNAs in a strict temporal order. In isolated animal oocytes, translation of maternal mRNAs containing a cytoplasmic polyadenylation element (CPE), such as cyclin B, is activated by in vitro stimulation of meiotic resumption which induces phosphorylation of CPEB (CPE-binding protein) and elongation of their polyadenosine (poly(A)) tails; whether or not this model can be applied in vivo to oocytes arrested at metaphase of meiosis I in ovaries is unknown. In this study, we found that active CDK1 (cyclin-dependent kinase 1) phosphorylated CPEB in ovarian oocytes arrested at metphase I in the starfish body cavity, but phosphorylation of CPEB was not sufficient for elongation of cyclin B poly(A) tails. Immediately after spawning, however, mRNA was polyadenylated, suggesting that an increase in intracellular pH (pHi ) upon spawning triggers the elongation of poly(A) tails. Using a cell-free system made from maturing oocytes at metaphase I, we demonstrated that polyadenylation was indeed suppressed at pH below 7.0. These results suggest that a pH-sensitive process, functioning after CPEB phosphorylation, is blocked under physiologically low pHi (<7.0) in metaphase-I-arrested oocytes. The increase in pHi (>7.0) that occurs after spawning triggers polyadenylation of cyclin B mRNA and progression into meiosis II.


[The prognostic significance of cytogenetic, morphological and clinical indices in patients with malignant skin melanoma].
Retrospective estimation of the prognostic importance of parameters, that are different in biological essence, for the persons that have died from malignant melanoma of the skin with use of the adequate mathematical approaches is carried out. A spectrum of important cytogenetic, morphologic and clinical factors which have influence on the prognosis of disease is determined. For group of living patients the prognosed survival time are individually calculated.


A fatal case of pontine hemorrhage related to methamphetamine abuse.
In this report, we describe a fatal case of pontine hemorrhage related with methamphetamine abuse. A 54-year-old male was found dead in a prone position in his parents' house, and a medico-legal autopsy was carried out to determine the cause of his death. Externally, although an injection mark-like injury with subcutaneous hemorrhage was observed in the left cubital fossa, the autopsy revealed no severe trauma leading to death. Internally, every organ was moderately congested. The brain weighed 1330 g. Macroscopically, there was no vascular abnormality such as aneurysm or malformation. In the sections of the brain stem, a massive hematoma occupied the central area of the pons. Drug screening test using Triage was weakly positive for amphetamines. Moreover, in the blood and urine samples, methamphetamine was quantitatively detected at concentrations of 0.4 and 0.6 mg/l, respectively, by gas chromatography-mass spectrometry. Other drugs and poison were not detected in the blood and urine samples collected at autopsy. Histopathologically, necrotizing angiitis characterized by fibrinoid necrosis of the intima and media was observed with cell infiltration. Thus, the pontine hemorrhage seemingly resulted from methamphetamine-induced angiitis, with an acute elevation of blood pressure after methamphetamine abuse.


Axon-myelin transfer of glycerol-labeled lipids and inorganic phosphate during axonal transport.
Axon-to-myelin transfer of lipids precursors have been studied in the rabbit optic system by intraocular injection of [32P]orthophosphate, [14C]glycerol and [3H]glycerol. Choline and ethanolamine phosphoglycerides and myelin showed increasing [32P]-radioactivity between 7 and 21 days following injection, while [3H]- and [14C]-radioactivities remained relative constant. The latter radioactivities decreased, however, in all the axon- and axolemma-enriched fractions during the same period. These findings supported the concept that a portion of substances undergoing axonal transport enters the pool of myelin lipids by two mechanisms: transcellular transfer of intact lipid and axon-myelin transfer of precursors which are re-utilized for lipid biosynthesis by myelin-localized enzymes. The present study shows that inorganic phosphate, possibly generated by catabolic activity within the axon, is able to enter myelin and participate in the re-utilization mechanism as previously described for serine, choline and acyl chains. The relative invariance of the 3H:14C ratio suggested that the majority of glycerol is not re-utilized in this manner but probably enters myelin through transfer of intact lipid. These and earlier results suggest a possible form of metabolic dependence of myelin on tropine substances from the axon.


Asymmetric warming reduces the strength of selection pressure of moderate grazing on reproductive phenology in alpine plants.
Both warming and grazing already affect the reproductive phenology of alpine plants. However, their effects have mostly been studied in isolation, and their interaction is still unclear. In this study, an asymmetric warming (average + 1.2 °C during daytime and + 1.7 °C during nighttime and + 1.5 °C during summer and + 2.0 °C during winter) with moderate grazing experiment was conducted for four years to determine their individual and interactive effects on the onsets and durations of reproductive phenophases for fifteen alpine plant species on the Qinghai-Tibetan Plateau. Individual warming and grazing simultaneously advanced the average start dates and ending dates of budding, flowering and fruiting by 5.3-6.2 days, and further resulted in smaller effects on their durations for most plant species. The interactions between warming and grazing on them varied with plant species and year, which advanced by average 12.1 days for all plant species. The effects of grazing on the temperature sensitivity of the start dates of reproductive phenophases (average by -8.5 days °C-1) were greater than that of warming alone (average by -3.4 days °C-1) and warming with grazing (average by -5.5 days °C-1) for most of the alpine plant species. There were significant effects of the previous phenological events on subsequent reproductive phenophases. Therefore, our results suggested that both warming and grazing advanced reproductive phenophases through altered soil temperature and soil moisture and carry-over effects of previous phenological events on subsequent phenological events. Warming reduced the temperature sensitivity of the start dates of reproductive phenophases to grazing, suggesting that it depressed strength of selection pressure of grazing on the onsets of reproductive phenology in alpine plants.


Overexpression of forkhead box protein M1 (FOXM1) plays a critical role in colorectal cancer.
The forkhead box M1 (FOXM1), an important regulator of cell differentiation and proliferation, is overexpressed in a number of aggressive human carcinomas. However, the clinical significance of FOXM1 signaling in human colorectal cancer (CRC) pathogenesis remains unknown. The aim of this study was to evaluate the role of FOXM1 in CRC tumorigenesis. We investigated FOXM1 expression in 103 cases of primary CRC and matched normal tissue specimens and explored the underlying mechanisms of altered FOXM1 expression and the impact of this altered expression on CRC proliferation and metastasis using in vitro models of CRC. The results showed that high expression of FOXM1 staining was 85.44% (88/103) in 103 cases of CRC and 20.39% (21/103) in 103 cases of adjacent non-cancerous tissue samples; the difference of FOXM1 expression between two groups was statistically significant (P < 0.001). Silencing of FOXM1 inhibited the proliferation of CRC cells, and the invasion and migration of CRC cells were distinctly suppressed. Furthermore, FOXM1 knockdown led to substantial reductions in VEGF-A levels in CRC cell lines. Our data suggest that the pathogenesis of CRC maybe mediated by FOXM1, and FOXM1 could represent selective targets for the molecularly targeted treatments of CRC.


Reduced venous compliance in normotensive men with positive family histories of hypertension.
To test the hypothesis of reduced venous compliance and increased cardiovascular responses to volume expansion and alpha-agonist stimulation. Non-hypertensive healthy young men with positive (PFH) and negative family histories of hypertension were investigated regarding peripheral haemodynamics and changes in central venous pressure (CVP) and arterial blood pressure in response to graded doses of phenylephrine and acute i.v. fluid volume loading (1000 saline solution in 10 min). The control group was divided into one group matched for body mass index to PFH subjects (NFHO) and one lean control group (NFHN). Supine blood pressure was higher in PFH and NFHO subjects compared with NFHN subjects, whilst CVP was similar in the three groups at baseline. No significant differences in calf or forearm haemodynamics or blood volume were observed between the three groups. Cardiovascular responses to bolus doses of phenylephrine did not differ between the three groups. Saline infusion significantly increased CVP and systolic blood pressure, and effective vascular compliance (change in blood volume: CVP ratio) was reduced in PFH subjects. PFH subjects have decreased effective vascular compliance and altered arterial blood pressure responses to acute increases in vascular fluid volume. This may result from multiple factors such as increased venous vascular tone, structural reduction of venous distensibility and/or an altered neurohormonal response to increased CVP.


Establishing Concurrent Mands for Items and Mands for Information about Location in Children with Autism.
This study replicated and extended the methodology used in Howlett et al. (Journal of Applied Behavior Analysis, 44, 943-947 2011) to bring the mands "Where's (item)?" and "I want (item)" under appropriate antecedent control in two boys diagnosed with autism. Trials were alternated in which items were present, missing, and within view (but inaccessible) and missing and out of view. To program for generalization, fifteen items, multiple trainers, and multiple settings were used during teaching. For both participants, manding generalized to novel items, instructors, settings, and situations and maintained after 2 weeks following teaching. Results of the social validity assessment indicated that school staff found the procedures highly acceptable.


Baseline and 1-year longitudinal data from the National Restless Legs Syndrome Opioid Registry.
Restless legs syndrome (RLS) is a sensory-motor neurological disorder. Low dose opioid medications are prescribed for treatment-refractory RLS. We describe baseline and 1-year longitudinal dosing and symptom outcomes for the National RLS Opioid Registry. Individuals currently taking a prescribed opioid for diagnosed RLS are included in the registry. Information on initial and current opioid dosages, side effects, past and current concomitant RLS treatments, RLS severity, psychiatric history, and opioid abuse risk factors were collected at baseline. Follow-up online surveys were performed at 6 months and 1-year. Participants (n = 500) are primarily white, elderly, educated, and retired. Half of all subjects are on opioid monotherapy. Nearly 50% of all subjects are taking methadone, and one-quarter are taking oxycodone formulations. The median total daily opioid dose is 30.0 morphine milligram equivalents (MME). At baseline, three-quarters of registry participants had been taking a prescribed opioid for RLS for more than 1 year and one-third for more than 5 years, and had mild-moderate RLS symptoms. At 1-year follow-up, 31.2% increased dose (median = 10 MME) and 16.0% decreased dose of their opioid. An MME increase ≥25 was associated with: opioid use for non-RLS pain, <1 year of opioid use, opioid switch to methadone, and discontinuation of non-opioid RLS medications which, combined, accounted for 91.7% of those with 1-year follow-up increases ≥25 MME. In refractory RLS, prescribed opioids are generally used at low doses with good efficacy. Longitudinally over 1 year, roughly one-third of participants increased their prescribed opioid dose, though generally by small amounts, with larger dose increases accounted for by predictable features.


Usefulness of early positive technetium-99m stannous pyrophosphate scan in predicting reperfusion after thrombolytic therapy for acute myocardial infarction.
To test the hypothesis that scans with technetium-99m pyrophosphate (Tc-99m-PPi) are positive when performed early after successful thrombolytic therapy for acute myocardial infarction (AMI), 16 consecutive patients with AMI who received thrombolytic therapy within 5 hours after the onset of chest pain were studied. Patients were included if chest pain lasted for greater than 30 minutes, was unresponsive to sublingual nitroglycerin and was associated with at least 0.2 mV ST-segment elevation in at least 2 contiguous electrocardiographic leads. All patients received 1.5 million IU of streptokinase intravenously, a mean of 195 +/- 99 minutes after onset of chest pain. Tc-99m-PPi scans and coronary cineangiograms were recorded 491 +/- 156 minutes and 518 +/- 202 minutes, respectively, after the onset of symptoms. Effective reperfusion was present in 10 patients, 6 of whom had positive Tc-99m-PPi scans (sensitivity of 60% to detect reperfusion). Of the 6 patients without effective reperfusion, 3 had positive Tc-99m-PPi scans (specificity of 50%, p greater than 0.05). Analysis of the data using various definitions of effective reperfusion or artery patency yielded similar results. Thus, our findings indicate that early AMI scanning with Tc-99m-PPi does not accurately detect the presence or absence of reperfusion in patients with AMI after treatment with intravenous streptokinase. At this time, coronary cineangiography is the only reliable method to detect reperfusion promptly after thrombolytic therapy.


Prognostic Value of Sex After Revascularization for Left Main Coronary Disease: Extended PRECOMBAT Study.
Female subjects have poorer outcomes in left main coronary artery (LMCA) disease compared with male subjects. However, limited information is available on the long-term prognostic impact of sex and sex-treatment interactions in patients with LMCA disease undergoing coronary revascularization. The goal of this study was to investigate the long-term effects of sex and related differential outcomes after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in LMCA disease. The extended PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease) trial evaluated the >10-year clinical outcomes in patients with LMCA disease randomized to undergo PCI with drug-eluting stents (n = 300) or CABG (n = 300). The primary outcome was major adverse cardiac or cerebrovascular events (MACCE) (composite of death, myocardial infarction, stroke, or ischemia-driven target vessel revascularization) at 10 years. Of the 600 patients, 459 (76.5%) were male. The 10-year rates of MACCE were similar between male and female subjects in the overall cohort (27.3% vs 27.0%; adjusted hazard ratio [aHR]: 1.06; 95% confidence interval [CI]: 0.70-1.59), the PCI arm (30.6% vs 27.1%; aHR: 1.19; 95% CI: 0.69-2.05), and the CABG arm (24.0% vs 26.9%; aHR: 0.93; 95% CI: 0.53-1.62). The 10-year risks for MACCE did not significantly differ between PCI and CABG in both male (aHR: 1.37; 95% CI: 0.95-1.97) and female (aHR: 1.07; 95% CI: 0.56-2.07) subjects. There was no significant sex-treatment interaction regarding the adjusted risk of MACCE at 10 years (P for interaction = 0.52). In this 10-year follow-up of the PRECOMBAT trial, there was no sex-related impact on the long-term risk of MACCE after PCI and CABG for LMCA disease. (Ten-Year Outcomes of PRECOMBAT Trial; NCT03871127).


In vitro selection and field responses of somaclonal variant plants of rice cv PR113 for drought tolerance.
Drought is the major environmental stress that limits rice productivity worldwide. In vitro somaclonal variation using different selection agents has been used for crop improvement. Here, rice plants of cv PR113 were selected in vitro on 30, 50 and 70 g L(-1) polyethylene glycol 6,000 (PEG). Callus growth, proliferation, calli volume (first and second culture) and plantlet regeneration (third culture) were found to be decreased upto a certain level to acquire tolerance to PEG-induced drought. From the field data, 30 g L(-1) PEG lines showed higher vegetative growth (plant height, tiller number, leaf number, shoot weight and root growth) as compared with 50 g L(-1) PEG selected somaclone lines under limited irrigation. The yield parameters-panicle length, panicle weight, grains per panicle, 1,000-grain weight, grain yield per plant, harvest index and grain straw ratio were also higher in 30 g L(-1) PEG lines as compared with 50 g L(-1) PEG lines. The results, therefore indicate that 30 g L(-1) PEG selected somaclone lines were more suited than 50 g L(-1) PEG selected somaclone lines under stress as compared with WT. The finding suggests that rice cv PR113 somaclones generated on PEG are found to be drought tolerant under field condition with better yield.