Evaluation of the VITEK 2 system to test the susceptibility of Candida spp., Trichosporon asahii and Cryptococcus neoformans to amphotericin B, flucytosine, fluconazole and voriconazole: a comparison with the M27-A3 reference method.
We compared the susceptibilities of 302 isolates (209 Candida spp., 89 Cryptococcus neoformans and four Trichosporon asahii) against amphotericin B (AMB), flucytosine (5FC), fluconazole (FLC) and voriconazole (VRC) obtained with an automated commercial system (VITEK 2, bioMérieux, Spain) and the Clinical and Laboratory Standards Institute (CLSI M27-A3) reference broth microdilution method (BMD). Reference BMD MIC endpoints were determined visually after 24-72 h of incubation, depending on the species, and VITEK 2 system MIC endpoints were determined spectrophotometrically by automated components of this equipment. For Candida spp. and T. asahii, the overall MIC agreement between of the results of the VITEK 2 system and the 24/48-h BMD was: 34/62% for AMB; 96.3% at 24/48-h for 5FC; 87.8/87.3% for FLC and 95.3/92% for VRC, respectively. The overall categorical agreement between both methods was: 98.5/97.6% for AMB at 24/48-h; 95.3% for 5FC at 24/48-h; 85.4/84.4% at 24/48-h for FLC; and 97.6/92.95% at 24/48-h for VRC. For C. neoformans, essential agreement was good for FLC (91%) and 5FC (84.2%) but not so good for AMB (69%). Excellent categorical agreement was obtained for all antifungal agents tested except for 5FC (69.7%). This new system could play an important role in the clinical laboratory, but more studies are necessary to verify its ability to identify resistant isolates.


Gastro-Intestinal Bleeding in COVID-19 Patients - Is There Any Causal Relation?
The novel Severe Acute Respiratory Syndrome Coronavirus-2 has put an enormous pressure on health systems around the world. The large number of severe cases that had symptoms seemingly unrelated to the respiratory system, continues to create confusion. The digestive tract is not spared either. The most commonly reported digestive symptoms are nausea, vomiting, anorexia, diarrhea and, less frequently but with significant impact, gastrointestinal bleeding. The elderly population is the one more likely to develop severe anemia clinically expressed by hematemesis, melena or hematochezia. From our experience and as we concluded from literature, men confirmed with COVID-19 have a higher risk of developing digestive haemorrhage. The upper gastro-intestinal tract, defined as the digestive segment above the Treitz angle, is more often affected. The gastro-duodenal ulcers are the main cause found in COVID-19 patients with digestive bleeding. In addition, the patients with SARS-COV2 infection and gastro-intestinal bleeding most commonly associate with other comorbidities such as hypertension and diabetes.


Myocardial protection during transient coronary artery occlusion in man: beneficial effects of regional beta-adrenergic blockade.
The goal of this study was to verify whether myocardial protection could be achieved via the intracoronary administration of propranolol in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Accordingly, 21 patients undergoing PTCA were randomly assigned to receive either intracoronary placebo (group A, n = 10) or intracoronary propranolol (group B, n = 11). Three balloon inflations (i.e., coronary artery occlusions) were performed in each patient. Inflations I and II (maximum duration 60 sec) served as control occlusions. Inflation III (maximum duration 120 sec) was performed either after intracoronary administration of saline (2 ml) or propranolol (1.1 +/- 0.2 mg). The following electrocardiographic index of myocardial ischemic injury were measured: (1) time to development of ST segment elevation equal to 0.1 mV and (2) magnitude of ST segment elevation after 60 sec of coronary artery occlusion. Both indexes did not differ significantly between the groups during inflations I and II. In group A the time to development of ST segment elevation of 0.1 mV remained unchanged between the second and third occlusions (25 +/- 5 and 26 +/- 4 sec during inflations II and III, respectively). In group B subselective injection of propranolol into the affected coronary artery significantly prolonged the time to ST segment elevation of 0.1 mV from 19 +/- 4 sec (inflation II) to 53 +/- 9 sec (inflation III; p less than .001). Administration of placebo did not change the magnitude of ST segment elevation 60 sec after coronary artery occlusion between the second and third occlusion in group A (0.16 +/- 0.02 and 0.18 +/- 0.03 mV, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


[HCV genotyping in health professionals: controversies and perspectives].
Healthcare workers (HCW) are at risk of acquiring blood-borne infections, including HCV Although current evidence does not suggest an increased prevalence of HCV infection among HCW, transmission of infection following occupational exposure has been demonstrated. Moreover, HCV can establish a persistent, chronic infection contributing to progressive liver disease, and post-exposure prophylaxis against HCV infection is not currently available. Problems still arise in the health surveillance of healthcare workers HCV infected. The use of virologic assays has become essential in the management of hepatitis C virus (HCV) infection, in order to improve the diagnosis of the infection, to guide the treatment decisions, and to assess the virologic response to antiviral therapy. Although several studies have specifically evaluated the role of HCV genotypes, many questions have not been answered. It is thought that HCV genotypes are important epidemiological markers, but more investigations are needed to elucidate their role regarding the progression and the pathogenesis of liver disease. The clinical implication of HCV genome heterogeneity, the different genotyping methods and the possible role of HCV genotypes as a parameter that could help health surveillance of infected HCW are described in this paper.


New drugs in therapy of colorectal cancer: preclinical studies.
For years, 5-fluorouracil (5-FU) was the only chemotherapeutic agent for the treatment of patients with advanced colorectal cancer. Based on laboratory data, modulation of 5-FU by leucovorin (LV) was proven to be an active alternative. In addition, a number of 5-FU prodrugs and antifolate antimetabolites became available for preclinical and clinical evaluation. With the 5-FU prodrugs, the overall aim was to improve the therapeutic efficacy and selectivity of 5-FU and to provide an oral form of therapy. In preclinical systems, several of the 5-FU prodrugs, eg, capecitabine, uracil/ ftorafur (UFT)/LV, and S- , are active and offer significant therapeutic advantages over 5-FU/LV. A direct and specific new thymidylate synthase (TS) inhibitor, Tomudex (raltitrexed, ZDI694; Zeneca Pharmaceuticals, Macclesfield, UK), is active in several preclinical and clinical settings. The major focus of this report will be on the preclinical development of selected fluoropyrimidine prodrugs.


Correlates of negative attitudes toward gay men: sexism, male role norms, and male sexuality.
Research has shown that heterosexual men are more negative toward gay men than women are on measures of attitudes toward homosexual behaviour and homosexual persons (Kite & Whitley, 1996). Gender differences in attitudes toward gay men's civil rights are less clear. No empirical studies, however, have investigated these findings with a scale that measures specifically these three attitudinal subcomponents. This study was a preliminary test of a scale that measured these subcomponents. In addition, this study investigated the relationship between these subcomponents and other attitudinal measures: hostile sexism, male toughness, and attitudes toward male sexuality. Results revealed that attitudes toward homosexual behaviour and homosexual persons comprised one factor: affective reactions toward gay men. Results showed that men were more negative on affective reactions than women were. No gender differences were revealed on attitudes toward civil rights. I found significant correlations between affective reactions, hostile sexism, male toughness, and male sexuality. I discuss these findings in relation to traditional gender role beliefs and make suggestions for future research.


Management of cluster headache: Treatments and their mechanisms.
The management of cluster headache is similar to that of other primary headache disorders and can be broadly divided into acute and preventive treatments. Acute treatments for cluster headache are primarily delivered via rapid, non-oral routes (such as inhalation, nasal, or subcutaneous) while preventives include a variety of unrelated treatments such as corticosteroids, verapamil, and galcanezumab. Neuromodulation is becoming an increasingly popular option, both non-invasively such as vagus nerve stimulation when medical treatment is contraindicated or side effects are intolerable, and invasively such as occipital nerve stimulation when medical treatment is ineffective. Clinically, this collection of treatment types provides a range of options for the informed clinician. Scientifically, this collection provides important insights into disease mechanisms. Two authors performed independent narrative reviews of the literature on guideline recommendations, clinical trials, real-world data, and mechanistic studies. Cluster headache is treated with acute treatments, bridge treatments, and preventive treatments. Common first-line treatments include subcutaneous sumatriptan and high-flow oxygen as acute treatments, corticosteroids (oral or suboccipital injections) as bridge treatments, and verapamil as a preventive treatment. Some newer acute (non-invasive vagus nerve stimulation) and preventive (galcanezumab) treatments have excellent clinical trial data for episodic cluster headache, while other newer treatments (occipital nerve stimulation) have been specifically tested in treatment-refractory chronic cluster headache. Most treatments are suspected to act on the trigeminovascular system, the autonomic system, or the hypothalamus. The first-line treatments have not changed in recent years, but new treatments have provided additional options for patients.


Why Humans Fail in Solving the Monty Hall Dilemma: A Systematic Review.
The Monty Hall dilemma (MHD) is a difficult brain teaser. We present a systematic review of literature published between January 2000 and February 2018 addressing why humans systematically fail to react optimally to the MHD or fail to understand it. Based on a sequential analysis of the phases in the MHD, we first review causes in each of these phases that may prohibit humans to react optimally and to fully understand the problem. Next, we address the question whether humans' performance, in terms of choice behaviour and (probability) understanding, can be improved. Finally, we discuss individual differences related to people's suboptimal performance. This review provides novel insights by means of its holistic approach of the MHD: At each phase, there are reasons to expect that people respond suboptimally. Given that the occurrence of only one cause is sufficient, it is not surprising that suboptimal responses are so widespread and people rarely understand the MHD.


Uveitis as a Risk Factor for Developing Acute Myocardial Infarction in Ankylosing Spondylitis: A National Population-Based Longitudinal Cohort Study.
Ankylosing spondylitis (AS) is a chronic inflammatory disease. Excess cardiovascular risks were well recognized in patients with AS and were attributed to prolonged systemic inflammation. Uveitis is one of the most common extra-articular symptoms of AS and is also considered an indicator of systemic inflammation. This study aimed to investigate whether uveitis was a risk factor for developing acute myocardial infarction (AMI) in patients with AS using the National Health Insurance Research Database (NHIRD). Data were collected from the NHIRD over a fifteen-year period. Variables were analyzed using the Pearson chi-square test and Fisher's exact test. Risk factors for the occurrence of AMI were examined by calculating hazard ratio. Kaplan-Meier analysis was performed to compare the cumulative incidence of AMI in the uveitis and non-uveitis cohorts. A total of 5905 patients with AS were enrolled, including 1181 patients with uveitis (20%) and 4724 patients without uveitis (80%). The Kaplan-Meier method with the log-rank test showed that the uveitis group had a significantly higher cumulative hazard for patients with AMI than the non-uveitis group (p < 0.001). The adjusted hazard ratio (aHR) of AMI was higher in the uveitis group than in the non-uveitis group (aHR = 1.653, p < 0.001). Stratified analysis revealed that patients with uveitis had an increased risk of developing AMI regardless of their sex (male/female aHR = 1.688/1.608, p < 0.001). Patients with uveitis in all age groups were independently associated with an increased risk of developing AMI compared to those without uveitis (20-39 years/40-59 years/≥ 60 years, aHR = 1.550, 1.579, 3.240, p < 0.001). Patients with uveitis had a higher probability of developing AMI regardless of comorbidities. Uveitis patients with comorbidities had a higher risk of developing AMI compared to uveitis patients without comorbidities. Uveitis is a significant risk factor for developing AMI in patients with AS. Physicians should be aware of the potential cardiovascular risk in AS patients with uveitis, especially simultaneously with other traditional risk factors of AMI. Further prospective studies are needed to elucidate the underlying mechanism between uveitis and AMI in patients with AS.


Small traveling clusters in attractive and repulsive Hamiltonian mean-field models.
Long-lasting small traveling clusters are studied in the Hamiltonian mean-field model by comparing between attractive and repulsive interactions. Nonlinear Landau damping theory predicts that a Gaussian momentum distribution on a spatially homogeneous background permits the existence of traveling clusters in the repulsive case, as in plasma systems, but not in the attractive case. Nevertheless, extending the analysis to a two-parameter family of momentum distributions of Fermi-Dirac type, we theoretically predict the existence of traveling clusters in the attractive case; these findings are confirmed by direct N -body numerical simulations. The parameter region with the traveling clusters is much reduced in the attractive case with respect to the repulsive case.


HGH behaviour at term of pregnancy and during puerperium.
Human growth hormone (HGH) has been measured in the plasma of 30 subjects at term of pregnancy, at 96 and at 144 h after delivery. The subjects were then selected into three groups: 10 were studied in basal conditions, 10 were given pyridoxine, 10 were given enantate testosterone and valerianate estradiol. In the first group the correlation index (t of Student) was not significant showing the lack of correlation among the tested averages. IN the second group the index of Student was weakly significant (t = 2.36, p less than 0.05). In the third group the Authors found a high representative correlation between the term of pregnancy and the 144th hour after delivery (t = 3.81, p less than 0.01) and between the 96th and 144th hour after delivery (t = 2.95, p less than 0.01).


Fine-needle aspiration biopsy in a pediatric population. Report of 64 consecutive cases.
Fine-needle aspiration biopsy for diagnosis of mass lesions has seldom been used in pediatric patients. Sixty-four aspirations from pediatric patients have been reviewed in order to determine the adequacy of this technique in the pediatric age group. There were 38 benign diagnoses, 19 malignant diagnoses, and 7 unsatisfactory specimens. The benign diagnoses included inflammatory lesions, benign tumors, cystic lesions, and miscellaneous lesions. The malignant diagnoses included neuroblastomas, leukemias or lymphomas, small cell or poorly differentiated tumors, Wilms' tumors, rhabdomyosarcomas, a Ewing's sarcoma, and a postirradiation fibrosarcoma. Correlation of histologic and cytologic diagnoses was possible in 53 cases. The diagnostic sensitivity and specificity for the detection of malignant disease were 76% and 100%, respectively. These results suggest that fine-needle aspiration biopsy is a useful technique in the diagnosis of pediatric mass lesions.


[Expression and clinical significance of MTA1 in non-small cell lung cancer.].
Metastasis-associated gene 1 (MTA1 ) has been studied deeply recently as a tumor infiltration and metastasis gene. It was expressed in many tumor cell line and was correlated with tumor infiltration and metastasis. The aim of this study is to investigate the relationship between the expression of MTA1 and invasion and metastasis of non-small cell lung cancer (NSCLC). Optimal conditions of nested reverse transcription polymerase chain reaction (RT-PCR) were found out; then the expression of MTA1 mRNA in 42 samples of primary carcinoma tissues, paracancerous tissues, normal tissues and corresponding lymph nodes were compared with 20 lung innocence tissues at semi-quantitative level and the results were compared with clinical pathologic data. Average expression of the MTA1 gene in NSCLC primary carcinoma tissue (1.50+/-0.26) and lymph nodes with metastasis (1.88+/-0.35) was remarkably higher than that in normal tissue (1.02+/-0.17) and lung innocence tissue (0.90+/-0.15) (P <0.01). Average expression of the MTA1 gene in NSCLC primary carcinoma tissue (1.50+/-0.26) was significantly higher than that in paracancerous tissue (1.09+/-0.16). Average expression of the MTA1 gene in lymph nodes with metastasis (1.88+/-0.35) was significantly higher than that in those without metastasis (1.40+/-0.36) (P <0.01). The frequency of MTA1 overexpression in NSCLC tissue was closely correlated with clinical staging, T staging and N staging; the frequency of MTA1 overexpression was 45.2% (19/42) in NSCLC tissue. The frequency of MTA1 overexpression was 84.2% (16/19) in lymph nodes with metastasis. The expression level of MTA1 gene in cancer tissues was not related to age, gender of the patients and type of tumor. Our data suggests that the overexpression of the MTA1 gene correlates with invasion and metastasis of NSCLC. A high expression of MTA1 mRNA may be a potential indicator for assessing the malignancy and metastasis of NSCLC.


Using an interview guide to assess suicidal ideation.
More than 50% of Americans who commit suicide have seen their primary care provider in the weeks before their suicide. As primary care providers, we may miss opportunities to assess for suicidal ideation. Here, we present an interview guide that helps assess suicidal ideation in primary care patients.


The use of intramedullary nails in tibiotalocalcaneal arthrodesis.
Tibiotalocalcaneal arthrodesis is a salvage procedure undertaken for hindfoot problems that affect both the ankle and subtalar joints (eg, two-joint arthritis, severe acute trauma, osteonecrosis of the talus, severe malalignment deformities, significant hindfoot bone loss). Methods of achieving fusion include Steinmann pins, screws, plates, external fixators, and retrograde intramedullary nailing. Retrograde intramedullary nailing provides a load-sharing fixation device with superior biomechanical properties and is an excellent choice for use in tibiotalocalcaneal arthrodesis. This technique can be performed through relatively small incisions. In addition, recent design modifications include the availability of dynamization and the choice of curved or straight nails. Contraindications to the technique include the presence of infection, severe vascular disease, and severe malalignment of the tibia.


On the possible role of brain rhythms in speech perception: intelligibility of time-compressed speech with periodic and aperiodic insertions of silence.
This study was motivated by the prospective role played by brain rhythms in speech perception. The intelligibility - in terms of word error rate - of natural-sounding, synthetically generated sentences was measured using a paradigm that alters speech-energy rhythm over a range of frequencies. The material comprised 96 semantically unpredictable sentences, each approximately 2 s long (6-8 words per sentence), generated by a high-quality text-to-speech (TTS) synthesis engine. The TTS waveform was time-compressed by a factor of 3, creating a signal with a syllable rhythm three times faster than the original, and whose intelligibility is poor (<50% words correct). A waveform with an artificial rhythm was produced by automatically segmenting the time-compressed waveform into consecutive 40-ms fragments, each followed by a silent interval. The parameters varied were the length of the silent interval (0-160 ms) and whether the lengths of silence were equal ('periodic') or not ('aperiodic'). The performance curve (word error rate as a function of mean duration of silence) was U-shaped. The lowest word error rate (i.e., highest intelligibility) occurred when the silence was 80 ms long and inserted periodically. This is also the condition for which word error rate increased when the silence was inserted aperiodically. These data are consistent with a model (TEMPO) in which low-frequency brain rhythms affect the ability to decode the speech signal. In TEMPO, optimum intelligibility is achieved when the syllable rhythm is within the range of the high theta-frequency brain rhythms (6-12 Hz), comparable to the rate at which segments and syllables are articulated in conversational speech.


Expression of the human angiotensinogen gene in human cell lines.
The human angiotensinogen gene consists of five exons interrupted by four introns and spans 12 kilobases. The gene is expressed in liver and HepG2 cells derived from human hepatoma. To examine whether the angiotensinogen gene is expressed in extrahepatic cells, RNAs from kidney and several human cell lines have been isolated and analyzed by Northern blot hybridization with the cloned gene as a probe. The mRNA for angiotensinogen was detected in human kidney and human glioblastoma (A-172) cells. To investigate the endogenous regulation of angiotensinogen gene expression, HepG2 cells were cultured in the presence of 3-aminobenzamide, a specific inhibitor of poly(ADP-ribose) polymerase. The expression of the angiotensinogen gene was demonstrated to be completely suppressed by 3-aminobenzamide (10 mM).


Physiological concentrations of tissue factor pathway inhibitor do not inhibit prothrombinase.
Tissue factor pathway inhibitor (TFPI) is a Kunitz-type serine proteinase inhibitor that directly inhibits factor Xa and, in a factor Xa dependent manner, inhibits the factor VIIa/tissue factor catalytic complex. The inhibitory effect of TFPI in prothrombin activation assays using purified components of the prothrombinase complex was examined. When factor Xa is added to mixtures containing TFPI, prothrombin, calcium ions, and nonactivated platelets or factor V and phospholipids, TFPI significantly reduces subsequent thrombin generation, and the inhibitory effect is enhanced by heparin. If factor Xa is preincubated with calcium ions and thrombin-activated platelets or factor Va and phospholipids to permit formation of prothrombinase before the addition of prothrombin and physiologic concentrations of TFPI (< 8 nmol/L), minimal inhibition of thrombin generation occurs, even in the presence of heparin. Thus, contrary to results in amidolytic assays with chromogenic substrates, prothrombinase is resistant to inhibition by TFPI in the presence of its physiological substrate, prothrombin. Higher concentrations of TFPI (approximately 100 nmol/L), similar to those used in animal studies testing for therapeutic actions of TFPI, do effectively block prothrombinase activity.


Acetaminophen plus codeine compared to ketorolac in polytrauma patients.
The management of pain in polytrauma patients is mandatory. While non-steroidal anti-inflammatory drugs (NSAIDs) represent the most used drugs in polytrauma patients, their use may be associated with an increased risk of haemorrhage. Opioids may represent a valid alternative to NSAIDs either alone or in combination with acetaminophen. Whether their efficacy is comparable to that produced by NSAIDs in polytrauma patients has never been studied. 60 polytrauma patients were enrolled for this study. 30 patients were treated with acetaminophen 1000 mg plus codeine 60 mg tid for 24 hours (Group A), while the remaining 30 with ketorolac 10 mg qid for 24 hours (Group B). Pain intensity has been evaluated using an analogical visual scale (VAS) ranging from 0 (no pain) to 10 (very severe pain). The level of pain was valuated at enrolment (TO) as well as after 2 (T2), 12 (T12) and 24 (T24) hours from the starting of the analgesic therapy. Results obtained by the group A were compared with those reported by the group B. T0: Group A mean score was 6.4 +/- 1.5 compared with 6.6 +/- 1.5 of Group B (p= ns); T2: Group A mean score was 3.4 +/- 2.8, compared with 3.5 +/- 2.4 of group B (p = ns); T12: Group A mean score was 3.4 +/- 3.4, compared with 3.5 +/- 3 of Gorup B (p = ns); T24: Group A mean score was 2.9 +/- 1.5, compared to 3.0 +/- 1.6 of Group B (p = ns). All those drugs determined a significant reduction of pain intensity during the course of therapy. Acetaminophen plus codeine is effective in pain control in polytrauma patients at least in our series. It may represent a valid alternative to NSAIDs, especially in patients with a documented haemorrhage or with a high hemorrhagic risk.


Morphometric Comparison of the Pterional Trans-Sylvian and the Pretemporal Trans-Clinoidal Approaches to the Posterior Communicating Artery.
Posterior communicating (Pcom) aneurysms in the modern era have tended toward increased complexity and technical difficulties. The pretemporal approach is a valuable extension to the pterional approach for basilar apex aneurysms, but its advantages for Pcom aneurysms have not been previously elucidated. To quantify characteristics of the pretemporal approach to the Pcom. We dissected 6 cadaveric heads (12 sides) with a pretemporal transclinoidal approach and measured the following variables: (1) exposed length of internal carotid artery (ICA) proximal to the Pcom artery; (2) exposed circumference of ICA at the origin of Pcom; (3) deep working area between the optic nerve and tentorium/oculomotor nerve; (4) superficial working area; (5) exposure depth; and (6) the frontotemporal (superior posterolateral) and (7) orbito-sphenoidal (inferior anterolateral) angles of exposure. Compared with pterional craniotomy, the pretemporal transclinoidal approach increased the exposed length of the proximal ICA from 3.3 to 11.7 mm (P = .0001) and its circumference from 5.1 to 7.8 mm (P = .0003), allowing a 210° view of the ICA (vs 137.9°). The deep and superficial working areas also significantly widened from 53.7 to 92.4 mm2 (P = .0048) and 252.8 to 418.2 mm2 (P = .0001), respectively; the depth of the exposure was equivalent. The frontotemporal and spheno-Sylvian angles increased by 17° (P = .0006) and 10° (P = .0037), respectively. The pretemporal approach can be useful for complex Pcom aneurysms by providing easier proximal control, wider working space, improved aneurysm visualization, and more versatile clipping angles. Enhanced exposure results in a potentially higher rate of complete aneurysm obliteration and complication avoidance.


Default mode network gates the retrieval of task-irrelevant incidental memories.
Episodic memories can be retrieved by an intentional search for certain information. Alternatively, a past episode may enter our consciousness without any intention to retrieve it, prompted by a stimulus in our surroundings. Incidental retrieval does not occur upon each encounter with a familiar stimulus, suggesting that a gating mechanism exists which regulates incidental retrieval activity. We analyzed data from a functional magnetic resonance imaging study on incidental retrieval in healthy young adults and found that failure to incidentally retrieve was selectively associated with reduced activation of lateral and medial parietal regions as well as ventromedial frontal cortex, areas implicated in default mode network. This is the first demonstration that relative deactivation of the brain regions associated with the default mode gates the consciousness from currently irrelevant memories.


IRS-1/PI3K/Akt pathway and miRNAs are involved in whole grain highland barley (Hordeum vulgare L.) ameliorating hyperglycemia of db/db mice.
The effects of whole grain highland barley (WGH) with rich phenolics on glucose metabolism, the insulin pathway, and microRNA (miRNA) expression in db/db mice were explored in the present study. Supplementation with WGH decreased the levels of blood glucose, glycosylated serum protein (GSP), insulin, and inflammatory cytokines in db/db mice. Furthermore, WGH administration triggered a remarkable amelioration of glucose intolerance and insulin resistance. The hepatic glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxylase (PEPCK) activities and the G6PC, PEPCK, and forkhead transcription factor 1 (FOXO1) mRNA levels in the WGH-treated group were also reduced. Moreover, WGH promoted the glycogen storage in the liver via up-regulating the activities of hexokinase (HK) and glycogen synthase (GS) and the phosphorylation of glycogen synthase kinase 3β (GSK3β) protein, while down-regulating the GSK3β mRNA level. The protein expression of phosphatidylinositol 3-kinase (PI3K), the phosphorylation of protein kinase B (Akt), and the mRNA levels of insulin receptor substrate-1 (IRS-1), PI3K and Akt were also up-regulated by WGH treatment. Moreover, WGH significantly augmented the expression of miRNA-26a and miRNA-451, but reduced those of miRNA-126a and miRNA-29a. These results demonstrated that WGH exhibits a hypoglycemic effect through regulating the IRS-1/PI3K/Akt pathway and related miRNAs, further modulating the expression of G6PC, PEPCK, and FOXO1 mRNAs and p-GSK3β protein, thus inhibiting hepatic gluconeogenesis, improving glycogen synthesis and alleviating insulin resistance. Therefore, this study suggested WGH as an effective candidate to ameliorate the hyperglycemia of type 2 diabetes mellitus.


Grip and detachment of locusts on inverted sandpaper substrates.
Locusts (Locusta migratoria manilensis) are characterized by their strong flying and grasping ability. Research on the grasping mechanism and behaviour of locusts on sloping substrates plays an important role in elucidating the mechanics of hexapod locomotion. Data on the maximum angles of slope at which locusts can grasp stably (critical angles of detachment) were obtained from high-speed video recordings at 215 fps. The grasping forces were collected by using two sensors, in situations where all left legs were standing on one and the right legs on the other sensor plate. These data were used to illustrate the grasping ability of locusts on slopes with varying levels of roughness. The grasping morphologies of locusts' bodies and tarsi were observed, and the surface roughness as well as diameters of their claw tips was measured under a microscope to account for the grasping mechanism of these insects on the sloping substrate. The results showed that the claw tips and part of the pads were in contact with the inverted substrate when the mean particle diameter was in the range of 15.3-40.5 µm. The interaction between pads and substrates may improve the stability of contact, and claw tips may play a key role in keeping the attachment reliable. A model was developed to explain the significant effects of the relative size of claw tips and mean particle diameter on grasping ability as well as the observed increase in lateral force (2.09-4.05 times greater than the normal force during detachment) with increasing slope angle, which indicates that the lateral force may be extremely important in keeping the contact reliable. This research lays the groundwork for the probable design and development of biomimetic robotics.


Influenza A(H1N1) vaccination during early pregnancy transiently promotes hippocampal neurogenesis and working memory. Involvement of Th1/Th2 balance.
The 2009 influenza A(H1N1) pandemic led to a particularly high risk of morbidity and mortality among pregnant women. Therefore, inactivated influenza vaccines have been widely recommended for women in any period of gestation. Recent studies have shown that the peripheral adaptive immune system plays an important role in the function of the central nervous system (CNS). The present study was conducted to explore if influenza vaccination, aiming to induce protective immune activation, affects maternal neurogenesis and cognitive ability. The results showed that A(H1N1) pregnant mice (AIV+Pre) had superior spatial working memory performance compared with pregnant controls (Pre). At the cellular level, a transient increase in both cell proliferation and neuronal differentiation in the dentate gyrus (DG) was found in the AIV+Pre group compared with the Pre group when BrdU was injected on gestational day 14 (G14). However, there were no obvious differences between A(H1N1) virgin mice (AIV+Vir) and virgin controls (Vir) in both hippocampal neurogenesis and working memory. Our findings further indicated that prolactin (PRL) concentrations were not overtly different between the AIV+Pre group and the Pre group at any time. Interestingly, IL-4 and IFN-γ levels were obviously increased both in the serum and hippocampus of the AIV+Pre group (with a T helper-1 like response; Th1) compared with the Pre group (with a T helper-2 like response; Th2) at G14, whereas the expression of IL-6 and TNF-α, the proinflammatory factors, was significantly reduced. Altogether, the results suggest that A(H1N1) vaccination during early pregnancy may contribute to adult hippocampal neurogenesis and spatial working memory and that the improvements were, at least in part, associated with Th1/Th2 balance.


A comparison of ground reaction forces determined by portable force-plate and pressure-insole systems in alpine skiing.
For the determination of ground reaction forces in alpine skiing, pressure insole (PI) systems and portable force plate (FP) systems are well known and widely used in previous studies. The purposes of this study were 1) to provide reference data for the vertical component of the ground reaction forces (vGRF) during alpine skiing measured by the PI and FP systems, and 2) to analyze whether the differences in the vGRF measured by the PI and the FP depend on a skier's level, skiing mode and pitch. Ten expert and ten intermediate level skiers performed 10 double turns with the skiing technique "Carving in Short Radii" as High Dynamic Skiing mode and "Parallel Ski Steering in Long Radii" as Low Dynamic Skiing mode on both the steep (23 °) and the flat (15 °) slope twice. All subjects skied with both the PI and the FP system simultaneously. During the outside phase, the mean vGRF and the maximum vGRF determined by the FP are greater than the PI (p < 0.01). Additionally during the inside phase, the mean vGRF determined by the FP were greater than the PI (p < 0.01). During the edge changing phases, the mean vGRF determined by the FP were greater than the PI (p < 0.01). However, the minimum vGRF during the edge changing phases determined by the FP were smaller than the PI (p < 0.01) in the High-Steep skiing modes of Experts and Intermediates (p < 0.001). We have found that generally, the PI system underestimates the total vGRF compared to the FP system. However, this difference depends not only the phase in the turn (inside, outside, edge changing), but also is affected by the skier's level, the skiing mode performed and pitch. Key pointsTypically, during the steering phases of the ski turns the total vGRFs measured by the pressure-insole system were lower compared to the portable force-plate system.However, in some skiing modes during the edge changing phase, the pressure-insole system overestimates the total vGRF compared to the portable force-plate system.Differences between the forces determined by the both systems depend on the phase in the turn (inside, outside, edge changing) and are affected additionally by the skier's level, the performed skiing mode and pitch.


High cervical intravagal hypercellular parathyroid gland as the etiology of severe persistent primary hyperparathyroidism.
The preoperative localization and operative management of a high cervical intravagal parathyroid adenoma in a young woman with severe persistent primary hyperparathyroidism is presented. The etiology of persistent hyperparathyroidism is most frequently a missed adenoma that is often in an ectopic location; of these, undescended adenomas represent a small but important proportion. If clinical suspicion and preoperative localization procedures suggest an undescended gland, a direct surgical approach using a high cervical incision and a unilateral exploration is often successful.


Adaptive illumination based on direct wavefront sensing in a light-sheet fluorescence microscope.
A methodology for the adaptive control and correction of phase aberrations in the illumination arm of a light-sheet fluorescence microscope has been developed. The method uses direct wavefront sensing on epi-fluorescent light to detect the aberration present in the sample. Using this signal, the aberrations in the illumination arm are subsequently corrected with a spatial light modulator in a feedforward mode. Adaptive correction, resulting in significant improvement in the axial resolution, has been demonstrated by imaging Tg(fli:GFP) zebrafish embryos.


A comparison of different antibiotic regimens for the treatment of infective endocarditis.
Infective endocarditis is a microbial infection of the endocardial surface of the heart. Antibiotics are the cornerstone of treatment, but their use is not standardised, due to the differences in presentation, populations affected and the wide variety of micro-organisms that can be responsible. To assess the existing evidence about the clinical benefits and harms of different antibiotics regimens used to treat people with infective endocarditis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE Classic and EMBASE, LILACS, CINAHL and the Conference Proceedings Citation Index on 30 April 2015. We also searched three trials registers and handsearched the reference lists of included papers. We applied no language restrictions. We included randomised controlled trials assessing the effects of antibiotic regimens for treating possible infective endocarditis diagnosed according to modified Duke's criteria. We considered all-cause mortality, cure rates and adverse events as the primary outcomes. We excluded people with possible infective endocarditis and pregnant women. Three review authors independently performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We constructed 'Summary of findings' tables and used GRADE methodology to assess the quality of studies. We described the included studies narratively. Four small randomised controlled trials involving 728 allocated/224 analysed participants met our inclusion criteria. These trials had a high risk of bias. Drug companies sponsored two of the trials. We were unable to pool the data due to the heterogeneity in outcome definitions and the different antibiotics used.The included trials compared the following antibiotic schedules. The first trial compared quinolone (levofloxacin) plus standard treatment (anti-staphylococcal penicillin (cloxacillin or dicloxacillin), aminoglycoside (tobramycin or netilmicin) and rifampicin) versus standard treatment alone reporting uncertain effects on all-cause mortality (8/31 (26%) with levofloxacin plus standard treatment versus 9/39 (23%) with standard treatment alone; RR 1.12, 95% CI 0.49 to 2.56, very low quality evidence). The second trial compared daptomycin versus low-dose gentamicin plus an anti-staphylococcal penicillin (nafcillin, oxacillin or flucloxacillin) or vancomycin. This showed uncertain effects in terms of cure rates (9/28 (32.1%) with daptomycin versus 9/25 (36%) with low-dose gentamicin plus anti-staphylococcal penicillin or vancomycin, RR 0.89 95% CI 0.42 to 1.89; very low quality evidence). The third trial compared cloxacillin plus gentamicin with a glycopeptide (vancomycin or teicoplanin) plus gentamicin. In participants receiving gentamycin plus glycopeptide only 13/23 (56%) were cured versus 11/11 (100%) receiving cloxacillin plus gentamicin (RR 0.59, 95% CI 0.40 to 0.85; very low quality evidence). The fourth trial compared ceftriaxone plus gentamicin versus ceftriaxone alone and found no conclusive differences in terms of cure (15/34 (44%) with ceftriaxone plus gentamicin versus 21/33 (64%) with ceftriaxone alone, RR 0.69, 95% CI 0.44 to 1.10; very low quality evidence).The trials reported adverse events, need for cardiac surgical interventions, uncontrolled infection and relapse of endocarditis and found no conclusive differences between comparison groups (very low quality evidence). No trials assessed septic emboli or quality of life. Limited and very low quality evidence suggested that there were no conclusive differences between antibiotic regimens in terms of cure rates or other relevant clinical outcomes. However, because of the very low quality evidence, this needs confirmation. The conclusion of this Cochrane review was based on randomised controlled trials with high risk of bias. Accordingly, current evidence does not support or reject any regimen of antibiotic therapy for treatment of infective endocarditis.


Risk and resilience in military families experiencing deployment: the role of the family attachment network.
Deployment separation constitutes a significant stressor for U.S. military men and women and their families. Many military personnel return home struggling with physical and/or psychological injuries that challenge their ability to reintegrate and contribute to marital problems, family dysfunction, and emotional or behavioral disturbance in spouses and children. Yet research examining the psychological health and functioning of military families is scarce and rarely driven by developmental theory. The primary purpose of this theoretical paper is to describe a family attachment network model of military families during deployment and reintegration that is grounded in attachment theory and family systems theory. This integrative perspective provides a solid empirical foundation and a comprehensive account of individual and family risk and resilience during military-related separations and reunions. The proposed family attachment network model will inform future research and intervention efforts with service members and their families.


[Adult dermatomyositis with angiopathy and cecum perforation].
This previously healthy 43-year-old man was admitted to our hospital with a history of rash, dysphagia and severe myalgia for two months. Physical examination showed prominent edema and erythema over the face and the chest, scattered ulcerations on the trunk, and muscle atrophy most prominent proximally. Serum levels of muscle enzymes were remarkably increased. Two weeks of oral prednisolone therapy (40 mg/day) was not effective, and betamethasone intravenous pulse therapy (3 x 1000 mg) was followed by slight clinical improvement. However, 12 days after pulse therapy, he complained abdominal pain on the right lower quadrant. The surgical findings included peritonitis due to single perforation of the cecum. After operation, cyclosporine therapy was added and over the next 14 month a considerable clinical improvement was noted. Prednisolone was reduced from 80 mg to 10 mg daily. Biopsy specimens from ulcerated+ skin and perforated cecum showed prominent vascular abnormalities: arterial and venous intimal hyperplasia, occlusion of vessels by fibrin thrombi, and lymphocytic infiltration which affected veins of all sizes. The evidence strongly suggests that both skin ulcers and cecum perforation were caused by vasculitis and occlusion of vessels, which often seen in childhood dermatomyositis.


Span efficiency in hawkmoths.
Flight in animals is the result of aerodynamic forces generated as flight muscles drive the wings through air. Aerial performance is therefore limited by the efficiency with which momentum is imparted to the air, a property that can be measured using modern techniques. We measured the induced flow fields around six hawkmoth species flying tethered in a wind tunnel to assess span efficiency, ei, and from these measurements, determined the morphological and kinematic characters that predict efficient flight. The species were selected to represent a range in wingspan from 40 to 110 mm (2.75 times) and in mass from 0.2 to 1.5 g (7.5 times) but they were similar in their overall shape and their ecology. From high spatio-temporal resolution quantitative wake images, we extracted time-resolved downwash distributions behind the hawkmoths, calculating instantaneous values of ei throughout the wingbeat cycle as well as multi-wingbeat averages. Span efficiency correlated positively with normalized lift and negatively with advance ratio. Average span efficiencies for the moths ranged from 0.31 to 0.60 showing that the standard generic value of 0.83 used in previous studies of animal flight is not a suitable approximation of aerodynamic performance in insects.


Matricellular proteins: new molecular targets to prevent heart failure.
Matricellular proteins are highly expressed in reparative responses to pressure and volume overload, ischemia, oxidative stress after myocardial injury, and modulate the inflammatory and fibrotic process in ventricular remodeling, which leads to cardiac dysfunction and eventually overt heart failure. Generally, matricellular proteins loosen strong adhesion of cardiomyocytes to extracellular matrix, which would help cells to move for rearrangement and allow inflammatory cells and capillary vessels to spread during tissue remodeling. Among matricellular proteins, osteopontin (OPN) and tenascin-C (TN-C) are de-adhesion proteins and upregulate the expression and activity of matrix metalloproteinases. These matricellular proteins could be key molecules to diagnose cardiac remodeling and also might be targets for the prevention of adverse ventricular remodeling. This review provides an overview of the role of matricellular proteins such as OPN and TN-C in cardiac function and remodeling, as determined by both in basic and in clinical studies.


Urban stormwater harvesting for domestic water supply: a water evaluation and planning approach.
Renewable groundwater and surface water supplies are insufficient for the current worldwide urban population as water demand is increasing rapidly. Usage per capita in urban areas transcends 160 liters per day. Climate change is projected to increase water demand even more. Sources of surface water from stormwater runoff can be used to fulfill this requirement. The main objective of this work is to assess the water supply and demand in the dry conditions of the Coimbatore region, Tamil Nadu, India, and to use the water evaluation and planning method to create a model for supply and demand in the future. There are more than three dozen surface water bodies in and around the metropolitan center. Most sources are heavily encroached upon. By linking stormwater runoff from its respective elevation to the accessible surface water bodies, an additional water supply source can be obtained. By using the water evaluation and planning framework as a guide, models were developed to determine potential needs, and to compare demand and supply, water usage, lack of water use, and population coverage. The enhanced stormwater drainage system for Coimbatore city was designed in such a way that the various roads were connected to the major water bodies. The domestic water demand in the future is predicted to be around 27 million cubic feet (MCFT). Meanwhile, the possible amount of stormwater collected in the selected water bodies is predicted to be 50 million cubic meter (MCM) to 320 MCM. This study concluded that 100% of urban domestic water demand can be met if the urban stormwater is utilized by harvesting and storing in surface water bodies.


The upper-limb volumetric changes in breast cancer survivors with axillary web syndrome.
Whether upper-limb swelling is associated with axillary web syndrome (AWS) is unknown. We recruited unilateral breast cancer (BC) patients who were scheduled for surgical intervention and lymph node dissection. The pre-operative assessment and post-operative assessment 3-4 weeks after surgery evaluated the upper-limb circumferential measurements, segmental limb volume, pain scores, grasp, shoulder range of motion (ROM), shoulder muscle power and quality-of-life scores. In the control group, the peri-elbow volume and upper-arm volume were significantly higher post-operatively than pre-operatively. In the AWS group, no significant difference was found. In comparison with the control group, the AWS group had significantly more pain, less active ROM in shoulder abduction and a lower upper-limb volume at 0-10 cm proximal to the lateral epicondyle. The incidence of lymphedema was 9.9% and was not associated with AWS. AWS is a common morbidity of lymph node dissection and causes significant pain and restricted shoulder abduction in the affected limb in BC survivors. This study is the first to investigate post-operative upper-limb volumetric changes in BC survivors with and without AWS. Our findings are of great value for the clinical effect of AWS in BC survivors, for patient education, and for developing diagnostic tools for detecting AWS.


Human TLR8 Senses RNA From Plasmodium falciparum-Infected Red Blood Cells Which Is Uniquely Required for the IFN-γ Response in NK Cells.
During blood-stage malaria, the innate immune system initiates the production of pro-inflammatory cytokines, including IFN-γ, that are critical to host defense and responsible for severe disease. Nonetheless, the innate immune pathways activated during this process in human malaria remain poorly understood. Here, we identify TLR8 as an essential sensor of Plasmodium falciparum-infected red blood cells (iRBC). In human immune cells, iRBC and RNA purified from iRBC were detected by TLR8 but not TLR7 leading to IFN-γ induction in NK cells. While TLR7 and 9 have been shown to lead to IFN-γ in mice, our data demonstrate that TLR8 was the only TLR capable of inducing IFN-γ release in human immune cells. This unique capacity was mediated by the release of IL-12p70 and bioactive IL-18 from monocytes, the latter via a hitherto undescribed pathway. Altogether, our data are the first reported activation of TLR8 by protozoan RNA and demonstrate both the critical role of TLR8 in human blood-stage malaria and its unique functionality in the human immune system. Moreover, our study offers important evidence that mouse models alone may not be sufficient to describe the human innate immune response to malaria.


[The limit of reference range of TSH: long-term discussion and possibilities of modern diagnostic.]
The review considers problem of upper limit of reference interval of TSH that is discussed predominantly by endocrinologists out of laboratory community. The common values of 0.4-4.0 mE/l combine as a matter of fact two ranges: zone of practically full wellbeing (0.4-2.5 mE/l) and zone of latent pathology and/or high possibility of development of clinically significant hypothyroidism (2.5-4.0 mE/l). At one time, the proposal to diminish upper limit of reference interval provoked many discussions and on balance received no approval. However, no unanimity concerning this issue is still to be achieved. The article discusses data forcing medical specialists to be wary of values of TSH in the range of 2.5-4.0 mE/l. At the same time, the question is putted concerning suitability of using population reference intervals in the case of both of TSH and number of other indices of laboratory diagnostic.


Alpha Amylase Inhibitory Potential and Mode of Inhibition of Oils from Allium sativum (Garlic) and Allium cepa (Onion).
Alpha amylase inhibitors are used in the treatment of type II diabetes mellitus. Allium sativum and Allium cepa, widely consumed as spices have several medicinal uses which include their traditional use in the management of diabetes. This study was conducted to investigate the alpha amylase inhibitory potential and mode of inhibition of A. sativum and A. cepa oils. Oil was extracted from dried bulb of A. sativum and A. cepa by Soxhlet extraction. The α-amylase inhibitory potential of the 2 oils were evaluated. The mode of inhibition of the oils were determined from the lineweaver-burk plot and the kinetic parameters obtained from the lineweaver - burk plot. A. sativum oil had 58.13 ± 1.09 and 69.8 ± 1.11 percent inhibition at 5.0 and 7.0% concentrations respectively while A. cepa oil had 55.45 ± 1.35, 59.73 ± 1.11 and 65.21 ± 1.11 percent inhibition at 5.0, 7.5 and 10% concentrations respectively. The IC50 values for A. sativum oil, A. cepa oil and acarbose were 3.0 ± 0.02%, 4.4 ± 0.03% and 14.1 ± 0.09% respectively. The lineweaver - burk plot showed that the Vmax of the 2 oils did not change when compared with that of the no inhibitor (no oil) but the Km increased. These findings indicate that A. sativum and A. cepa oils are competitive inhibitors of α- amylase and can both be used in the treatment of type II diabetes mellitus. A. sativum oil is a better inhibitor than A. cepa oil.


Lack of increased serum interleukin-6 and soluble IL-6 receptor concentrations in patients with thyroid diseases following recombinant human interferon alpha therapy.
Serum interleukin-6 (IL-6) concentrations are frequently elevated in inflammatory thyroid diseases, such as subacute thyroiditis and amiodarone induced thyroiditis. We and others have recently observed that recombinant interferon-alpha (rIFN-alpha) therapy for chronic, active viral hepatitis and malignant disorders may induce thyroid dysfunction, including thyrotoxicosis secondary to thyroiditis. Serum IL-6 and its soluble receptor (sIL-6R) have been measured for the first time in patients with chronic active hepatitis receiving rIFN-alpha therapy. Studies were carried out in 37 patients treated with rIFN-alpha for chronic, active viral hepatitis. Thyroid function tests and serum IL-6 and sIL-6R were measured before and during rIFN-alpha therapy. Six patients developed inflammatory or destructive thyrotoxicosis confirmed by elevated serum free T4 or free T3 concentrations, suppressed serum thyroid-stimulating hormone (TSH) values, and a low thyroid radioactive iodine uptake. Serum IL-6 and sIL-6R concentrations were not elevated in these patients with rIFN-alpha-induced thyroiditis. These results suggest that serum IL-6 concentrations are not useful in differentiating between inflammatory thyrotoxicosis and hyperthyroidism induced by rIFN-alpha therapy as is the case in amiodarone-induced thyrotoxicosis. It is possible that rIFN-alpha therapy could be associated with an inhibitory effect of rIFN-alpha on the release of IL-6 from damaged thyroid cells and not on the basal secretion of IL-6.


Asset price and wealth dynamics as an adaptive belief system.
In this paper we study an asset pricing model with heterogeneous beliefs, wealth dynamics and time varying proportions. We derive the resulting deterministic nonlinear dynamic system and analyze the model with adaptive beliefs and switching mechanism in order to investigate bifurcations and global dynamics and thus consider the effects on wealth distribution among different types of agents. Our study aims at confirming that heterogeneity in beliefs may lead to complexity.


Is there a superior simulator for human anatomy education? How virtual dissection can overcome the anatomic and pedagogic limitations of cadaveric dissection.
Educators must select the best tools to teach anatomy to future physicians and traditionally, cadavers have always been considered the "gold standard" simulator for living anatomy. However, new advances in technology and radiology have created new teaching tools, such as virtual dissection, which provide students with new learning opportunities. Virtual dissection is a novel way of studying human anatomy through patient computed tomography (CT) scans. Through touchscreen technology, students can work together in groups to "virtually dissect" the CT scans to better understand complex anatomic relationships. This article presents the anatomic and pedagogic limitations of cadaveric dissection and explains what virtual dissection is and how this new technology may be used to overcome these limitations.


Individual differences in cognitive performance due to right hemisphere arousal.
The purpose of this study was to investigate the relationship between individual differences in cognition and asymmetric patterns of cortical arousal in normal right-handed adults. Leftward asymmetry on a chimeric faces task was correlated with the ability to recognise faces and facial expression, and certain aspects of social skill. The correlation with face and emotional expression recognition was significant only for subjects who reported using a non-verbal strategy. These results further support the role of the right hemisphere in various aspects of social cognition, but also point to the need to consider individual differences in strategies employed during task performance.


A profile of adolescents admitted to a private inpatient unit and mental health outcomes.
To characterise adolescents admitted to a voluntary adolescent inpatient unit and investigate treatment outcomes. A retrospective cohort design was employed. Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) pre- and post-admission scores were collected, measuring global functioning. Demographic variables such as age, gender, primary diagnosis, comorbidity and length of stay (LOS) were analysed. Data were collected from May 2017 to April 2018. All adolescents admitted to the inpatient unit were included. The majority of adolescents (n = 72; HoNOSCA data available on n = 57) were 16 years of age (26%), female (82%) and with a primary diagnosis of a mood disorder (57%). Most adolescents improved at the time of discharge. Self-injury and emotional symptoms had greater reductions according to clinician and adolescent-self-ratings (p < 0.01). Mean change (improvement) in HoNOSCA total score was 7.3 (SD 7.5) based on clinician ratings and 7.2 (SD 9.5) for adolescent-self-ratings. The mean LOS was 28 days (SD 15.8). The inpatient unit proved effective at meeting the needs of young people in terms of symptom stabilisation. Further research is needed to describe adolescent inpatient models of care, the operations and philosophies to better examine how these relate to treatment outcomes.


Nature and Hierarchy of Noncovalent Interactions in Gas-Phase Binary Complexes of Indole and Benzimidazole with Ethers.
Hierarchy among the weak noncovalent interactions such as van der Waals, electrostatic, hydrogen bonding, etc. dictates the secondary and tertiary structures of proteins as well as their interactions with various ligands. In this work, we investigate the competition between conventional (N-H···O) hydrogen bonds, unconventional (C-H···O) hydrogen bonds, and the van der Waals interaction in the model compounds of the chromophores of the amino acids, tryptophan, and histidine. These include indole (IND), benzimidazole (BIM), and its N-methylated analog (N-methylbenzimidazole, MBIM), which present multiple docking sites. The binary complexes of these molecules with ethers (dimethyl ether, diethyl ether, and tetrahydrofuran), which possess high proton affinity but lack acidic protons (thereby only act as hydrogen bond acceptors), are investigated. The complexes are formed in a supersonic jet and jointly studied by electronic and vibrational spectroscopy as well as quantum chemical calculations. Only the N-H···O bound structures are observed for the complexes of IND and BIM with ethers, although computations predict reasonably competent C-H···O type of structures. Remarkably, IND and BIM produce three (N-H···O) conformers with Me2O but single conformers with Et2O and THF. In the case of MBIM, which lacks a conventional hydrogen bond donor, no evidence for C(2)-H···O hydrogen bonds is seen; instead, the complexes are found to be bound purely by van der Waals interactions. The results indicate that strong N-H···O and even weak van der Waals interactions are thermodynamically favored over C(2)-H···O bound structures in these binary gas-phase complexes.


Liquid chromatographic determination of acifluorfen in soil and water.
An analytical method based on the use of a liquid chromatograph equipped with a UV detector was developed for the determination of acifluorfen in soil and water. Acifluorfen was extracted from soil in methanol-0.10N NaOH (80 + 20 v/v) and from water by partition with dichloromethane. Solvent partitioning and solid-phase extraction were used to separate acifluorfen from major interfering sample components. Average recoveries from soil at 1, 0.1, and 0.01 ppm fortification levels were 95.1 +/- 3.4, 92.6 +/- 2.9, and 73.9 +/- 3.0%, respectively. Recoveries from water spiked at levels from 0.01 to 1 ppm averaged 96.5 +/- 5.4%. Method limits of detection were 0.006 ppm in soil and 0.003 ppm in water.


[The malignant transformation of leukoplakia of the oral cavity. A review of the literature and clinical case reports].
After considering the leukoplakia as defined by the WHO, the authors examine the quantitative, qualitative, histopathologic and clinical aspects of leukoplastic lesions. Afterwards, the data concerning the incidence of the malignant evolution of leukoplakia are shown. Data that have been collected and shown during years of study and that are often discordant. For this reason a study on the literature since 1931 is carried out and all the possible causes that could have led to different results are mentioned. Than the authors, among 98 cases of leukoplakia, examine those that turned malignant. In five cases, after the first biopsy, the histopathological report found the presence of microcarcinoma while, in three other cases, in the follow-up, a malignant evolution was observed. This This study points out a percentage of malignant transformation of the leukoplakia equal to 2,94% in agreement with the study of Pindborg and Banoczy.


[Papillary tumors of the breast].
The term papilloma applies to benign proliferative epithelial breast lesions with a papillary architecture. The papillae in such lesions contain an arborizing fibrovascular core, glandular surface epithelium and a basal myoepithelial layer. A basement membrane encloses these structures. Papilloma may occur at any site in the ductal lobular system and according to its localization is subdivided into two types: solitary (central) papilloma which are located in the major nipple/subareolar ducts or large segmental ducts and multiple (peripheral) papillomas in cystically dilated terminal ductal lobular units (TDLU). Stromal changes, epithelial metaplasia and/or proliferations and neoplasia may alter the prototypical architecture. In a significant number of papillomas atypia can be identified which have to be classified as atypical proliferates of the ductal type. These lesions must be distinguished from the papillary type of ductal carcinoma in situ. Some 17% of all papilloma are associated with (synchronous) intraductal or invasive carcinoma, but these also act as an indicator for subsequent (metachronous) carcinoma. As a consequence, in minimally invasive biopsy papilloma has to be classified as B3 and usually has to be followed by surgical excision.


Quantifying factors limiting aerobic degradation during aerobic bioreactor landfilling.
A bioreactor landfill cell at Yolo County, California was operated aerobically for six months to quantify the extent of aerobic degradation and mechanisms limiting aerobic activity during air injection and liquid addition. The portion of the solid waste degraded anaerobically was estimated and tracked through time. From an analysis of in situ aerobic respiration and gas tracer data, it was found that a large fraction of the gas-filled pore space was in immobile zones where it was difficult to maintain aerobic conditions, even at relatively moderate landfill cell-average moisture contents of 33-36%. Even with the intentional injection of air, anaerobic activity was never less than 13%, and sometimes exceeded 65%. Analyses of gas tracer and respiration data were used to quantify rates of respiration and rates of mass transfer to immobile gas zones. The similarity of these rates indicated that waste degradation was influenced significantly by rates of oxygen transfer to immobile gas zones, which comprised 32-92% of the gas-filled pore space. Gas tracer tests might be useful for estimating the size of the mobile/immobile gas zones, rates of mass transfer between these regions, and the difficulty of degrading waste aerobically in particular waste bodies.


Improved Stable Drag Reduction of Controllable Laser-Patterned Superwetting Surfaces Containing Bioinspired Micro/Nanostructured Arrays.
Superwetting surfaces are widely used in many engineering fields for reducing energy and resistance loss. A facile and efficient method using laser etching has been used to fabricate and control superwettable drag reduction surfaces. Inspired by the self-cleaning theory of lotus leaves, we propose controllable patterned bionic superhydrophobic surfaces (BSSs) simulating the uneven micro/nanostructures of lotus leaves. The superhydrophobicity and drag reduction ratios at low velocities are highly improved using a laser ablation method on metal substrates. However, unstable air layers trapped on superhydrophobic surfaces are usually cut away by a high-velocity flow, which greatly reduces the drag reduction performance. The fabricated bionic superhydrophobic/hydrophilic surfaces (BSHSs) with alternated hydrophilic strips can build a large surface energy barrier to bind the three-phase contact line. It maintains the stable drag reduction by capturing the air bubbles attached to the hydrophilic strips at a high velocity. Three-dimensional simulation analysis and equipment to measure the weak friction of a self-assembled solid-liquid interface are used to explain the drag reduction mechanism and measure the drag reduction ratios at different flow speeds. BSSs achieve an improved drag reduction effect (maximum 52.76%) at a low velocity (maximum 1.5568 m/s). BSHSs maintain an improved and steady drag reduction effect at high speed. The drag reduction ratios can be maintained at about 30% at high speed, with a maximum value of 4.448 m/s. This research has broad application prospects in energy saving, liquid directional transportation, and shipping due to their robust superhydrophobic properties and stable drag reduction effect.


I heard that coming: event-related potential evidence for stimulus-driven prediction in the auditory system.
The auditory system has been shown to detect predictability in a tone sequence, but does it use the extracted regularities for actually predicting the continuation of the sequence? The present study sought to find evidence for the generation of such predictions. Predictability was manipulated in an isochronous series of tones in which every other tone was a repetition of its predecessor. The existence of predictions was probed by occasionally omitting either the first (unpredictable) or the second (predictable) tone of a same-frequency tone pair. Event-related electrical brain activity elicited by the omission of an unpredictable tone differed from the response to the actual tone right from the tone onset. In contrast, early electrical brain activity elicited by the omission of a predictable tone was quite similar to the response to the actual tone. This suggests that the auditory system preactivates the neural circuits for expected input, using sequential predictions to specifically prepare for future acoustic events.


Metapopulation dynamics and spatial heterogeneity in cancer.
With the advent of drugs targeting specific molecular defects in cancerous cells [Gorre, M. E., et al. (2001) Science 293, 876-880], it is important to understand the degree of genetic heterogeneity present in tumor cell populations and the rules that govern microdiversity in human cancer. Here, we first show that populations with different genotypes in genes influencing cell growth and programmed cell death coexist in advanced malignant tumors of the colon, exhibiting microsatellite instability. Detailed, physical mapping of the diverse populations shows them to be arranged in small, intermingling areas, resulting in a variegated pattern of diversity. Using computational modeling of the experimental data, we find that the coexistence between similar competitors is enhanced, instead of deterred, by spatial dynamics [Hanski, I. (1999) Metapopulation Dynamics (Oxford Univ. Press, New York)]. The model suggests a simple and plausible scenario for the generation of spatial heterogeneity during tumor progression. The emergence and persistence of the patterns of diversity encountered in the tumors can be generated without a need to invoke differences in mutation rates, neutrality of interactions, or separated time scales. We posit that the rules that apply to spatial ecology and explain the maintenance of diversity are also at work in tumors and may underlie tumor microheterogeneity.


Platelet-mediated alterations in cardiac cellular electrophysiology.
Recent clinical and experimental evidence indicates that platelet activation contributes to the arrhythmogenic effects of myocardial ischaemia, but little is known about the electrophysiological effects produced by controlled platelet activation under conditions of normal perfusion and how these might relate to effects during ischaemia. To investigate this, we studied changes in cardiac cellular electrophysiology and arrhythmogenesis during infusion of platelets [10(8)/ml] in isolated, perfused guinea-pig hearts during normal perfusion and global myocardial ischaemia. Hearts were studied in four groups: group A (n = 4) receiving frozen/thawed (activated) platelets; group B (n = 4) receiving normal platelets in the presence of 10(-9) M platelet activating factor (PAF); group C (n = 9) receiving buffer only during normal perfusion and myocardial ischaemia; group D (n = 9) receiving platelets during normal perfusion and myocardial ischaemia. Infusion of platelets (group D) had no effects during normal perfusion, but activated platelets (group A) decreased action potential duration (APD) from 165 +/- 1 ms to 138 +/- 5 ms (mean +/- SE) at 15 min of normal perfusion (P less than 0.02) and produced ventricular fibrillation (VF) in 3/4 at 21 +/- 1 min. Infusion of platelets in the presence of PAF (group B) produced similar reductions of APD during normal perfusion and VF in 2/4. During ischaemia, platelets (group D) increased the incidence of VF (100% vs 56% group C, P less than 0.05) and enhanced the ischaemia-induced reductions in APD (107 +/- 3 ms vs 121 +/- 5 ms (group C) P less than 0.05 at 15 min).(ABSTRACT TRUNCATED AT 250 WORDS)


Methamphetamine enhances cell-associated feline immunodeficiency virus replication in astrocytes.
Human immunodeficiency virus (HIV) infection among substance abusers is on the rise worldwide. Psychostimulants, and in particular methamphetamine (METH), have detrimental effects on the immune system as well as causing a progressive neurodegeneration, similar to HIV infection. Many Lentivirinae, including feline immunodeficiency virus (FIV), penetrate into the central nervous system early in the course of infection with astrocytes serving as a reservoir of chronic brain infection. We demonstrate that the FIV-Maryland isolate infects feline primary and cell line (G355-5)-cultured astrocytes only under cell-associated conditions. Infected astrocytes yielded a new astrocytotropic isolate, capable of cell-free infection (termed FIV-MD-A). This isolate contained four amino acid substitutions in the envelope polyprotein resulting in a change in net charge as compared to FIV-MD. Infection for both isolates was dependent upon a functional astrocyte CXCR4 receptor. Methamphetamine increased significantly FIV replication in feline astrocytes for cell-associated infection only, with no effect on peripheral blood mononuclear cells or astrocytes infected with FIV-MD-A. This viral replication was related to proviral copy number, suggesting the effect of METH is at the viral entry or integration into host genome levels, but not at the translational level. Thus, lentiviral infection of the brain in the presence of the psychostimulant METH may result in enhanced astrocyte viral replication, producing a more rapid and increased brain viral load.


Evidence for Somatic Hypersensitivity in Veterans With Gulf War Illness and Gastrointestinal Symptoms.
Over 25% of Persian Gulf War (PGW) veterans with Gulf War Illness (GWI) (chronic health symptoms of undetermined etiology) developed gastrointestinal (GI) (diarrhea and abdominal pain) and other somatic symptoms. Our study objective was to determine if veterans with GWI and GI symptoms exhibit heightened patterns of somatic pain perception (hypersensitivity) across nociceptive stimuli modalities. Participants were previously deployed GW Veterans with GWI and GI symptoms (n=53); veterans with GWI without GI symptom (n=47); and veteran controls (n=38). We determined pain thresholds for contact thermal, cold pressor, and ischemic stimuli. Veterans with GWI and GI symptoms showed lower pain thresholds (P<0.001) for each stimulus. There was also overlap of somatic hypersensitivities among veterans with GI symptoms with 20% having hypersensitivity to all 3 somatic stimuli. Veterans with GWI and GI symptoms also showed a significant correlation between mechanical visual analog scale abdominal pain ratings and heat pain threshold, cold pressor threshold, and ischemic pain threshold/tolerance. Our findings show that there is widespread somatic hypersensitivity in veterans with GWI/GI symptoms that is positively correlated with abdominal pain ratings. In addition, veterans with somatic hypersensitivity that overlap have the greatest number of extraintestinal symptoms. These findings may have a translational benefit: strategies for developing more effective therapeutic agents that can reduce and/or prevent somatic and GI symptoms in veterans deployed to future military conflicts.


Circulating antineuronal antibodies in small cell lung cancer.
Antibodies directed against neuronal cells were found in the serum of 10 out of 27 patients with small cell lung cancer (SCLC) by means of an indirect immunofluorescent test. Positive staining was found either in nuclei of neurons with sparing of nucleoli or in the cytoplasm only. Antibodies belonged to IgG or IgM. A comparison with a control group of 60 patients yielded a high specificity of the circulating antibodies for SCLC. Contrary to recent reports, we were not able to confirm an association between the existence of circulating antibodies against neurons and the incidence of neurologic paraneoplastic disorders.


Telecommunications with muon beams.
The properties of well-collimated beams of muons with energies in the range of 10(9) electron volts may be suited to some specialized needs in telecommunications. has been carried out at Argonne National Laboratory.


Intermittent facial swelling.
Intermittent facial swelling is an unusual presentation in the emergency department. The differential diagnosis may range from a variety of causes. Most common differential diagnosis is angio-oedema. However, more serious presentations such as superior venacaval obstruction must not be ignored. This case report presents a patient who was investigated in the hospital for 2 weeks (2 admissions) with intermittent facial swelling. He presented to the emergency department (3rd admission) and was diagnosed to have superior venacaval obstruction secondary to metastatic bronchogenic carcinoma. He underwent emergency endovascular stenting; however, he died within a few weeks.


Water treadmill exercise reduces equine limb segmental accelerations and increases shock attenuation.
Equine water treadmills (WTs) are growing in popularity because they are believed to allow for high resistance, low impact exercise. However, little is known about the effect of water height on limb loading. The aim of this study was to evaluate the effect of water height and speed on segmental acceleration and impact attenuation during WT exercise in horses. Three uniaxial accelerometers (sampling rate: 2500 Hz) were secured on the left forelimb (hoof, mid-cannon, mid-radius). Horses walked at two speeds (S1: 0.83 m/s, S2: 1.39 m/s) and three water heights (mid-cannon, carpus, stifle), with a dry WT control. Peak acceleration of each segment was averaged over five strides, attenuation was calculated, and stride frequency was estimated by the time between successive hoof contacts. Linear mixed effects models were used to examine the effects of water height, speed, and accelerometer location on peak acceleration, attenuation and stride frequency (p < 0.05). Peak acceleration at all locations was lower with water of any height compared to the dry control (p < 0.0001). Acceleration was reduced with water at the height of the stifle compared to mid-cannon water height (p = 0.02). Water at the height of the stifle attenuated more impact than water at the height of the cannon (p = 0.0001). Water immersion during treadmill exercise reduced segmental accelerations and increased attenuation in horses. WT exercise may be beneficial in the rehabilitation of lower limb injuries in horses.


Venous shear stress enhances platelet mediated staphylococcal adhesion to artificial and damaged biological surfaces.
We investigated the role of blood components in the adhesion of staphylococci to biological and artificial surfaces under well-defined flow conditions by using the Cone and Plate(let) Analyzer. An enzyme-linked immunosorbent assay-like binding assay with biotinylated bacteria determined the extent of bacterial adhesion to subendothelial extracellular matrix (ECM), polystyrene (PS) and adult bovine aortic endothelial (ABAE) cell monolayer. The presence of adsorbed plasma proteins on PS and ECM did not increase and in some cases reduced staphylococcal adhesion under flow conditions (200s(-1)). However, their presence on ABAE cells increased bacterial adhesion but to a level still lower than the adhesion to PS and ECM. In contrast, adhered platelets significantly increased staphylococcal adhesion to both PS and ECM, but did not affect the adhesion to ABAE cells. Furthermore, bacterial adhesion to the platelets coated ECM and PS under flow conditions (200s(-1)) was increased by 1.4 to 2.6-fold compare to static conditions. The platelet-enhanced bacterial adhesion was markedly inhibited by blockade of the platelet GPIb receptor. In conclusion, staphylococcal extensive adhesion to ECM and PS surfaces is increased by venous flow and mediated by surface adhered activated platelets via a GPIb dependent mechanism. On the other hand, ABAE cells demonstrated limited bacterial adhesion that is mediated by adsorbed plasma proteins. Our results suggest that under physiological venous flow conditions the intact vessel wall is less prone for bacterial adhesion than damaged vessel wall.


Candidate SNP Markers of Gender-Biased Autoimmune Complications of Monogenic Diseases Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters.
Some variations of human genome [for example, single nucleotide polymorphisms (SNPs)] are markers of hereditary diseases and drug responses. Analysis of them can help to improve treatment. Computer-based analysis of millions of SNPs in the 1000 Genomes project makes a search for SNP markers more targeted. Here, we combined two computer-based approaches: DNA sequence analysis and keyword search in databases. In the binding sites for TATA-binding protein (TBP) in human gene promoters, we found candidate SNP markers of gender-biased autoimmune diseases, including rs1143627 [cachexia in rheumatoid arthritis (double prevalence among women)]; rs11557611 [demyelinating diseases (thrice more prevalent among young white women than among non-white individuals)]; rs17231520 and rs569033466 [both: atherosclerosis comorbid with related diseases (double prevalence among women)]; rs563763767 [Hughes syndrome-related thrombosis (lethal during pregnancy)]; rs2814778 [autoimmune diseases (excluding multiple sclerosis and rheumatoid arthritis) underlying hypergammaglobulinemia in women]; rs72661131 and rs562962093 (both: preterm delivery in pregnant diabetic women); and rs35518301, rs34166473, rs34500389, rs33981098, rs33980857, rs397509430, rs34598529, rs33931746, rs281864525, and rs63750953 (all: autoimmune diseases underlying hypergammaglobulinemia in women). Validation of these predicted candidate SNP markers using the clinical standards may advance personalized medicine.


Screening and expression of genes from metagenomes.
Microorganisms are the most abundant and widely spread organisms on earth. They colonize a huge variety of natural and anthropogenic environments, including very specialized ecological niches and even extreme habitats, which are made possible by the immense metabolic diversity and genetic adaptability of microbes. As most of the organisms from environmental samples defy cultivation, cultivation-independent metagenomics approaches have been applied since more than one decade to access and characterize the phylogenetic diversity in microbial communities as well as their metabolic potential and ecological functions. Thereby, metagenomics has fully emerged as an own scientific field for mining new biocatalysts for many industrially relevant processes in biotechnology and pharmaceutics. This review summarizes common metagenomic approaches ranging from sampling, isolation of nucleic acids, construction of metagenomic libraries and their evaluation. Sequence-based screenings implement next-generation sequencing platforms, microarrays or PCR-based methods, while function-based analysis covers heterologous expression of metagenomic libraries in diverse screening setups. Major constraints and advantages of each strategy are described. The importance of alternative host-vector systems is discussed, and in order to underline the role of phylogenetic and physiological distance from the gene donor and the expression host employed, a case study is presented that describes the screening of a genomic library from an extreme thermophilic bacterium in both Escherichia coli and Thermus thermophilus. Metatranscriptomics, metaproteomics and single-cell-based methods are expected to complement metagenomic screening efforts to identify novel biocatalysts from environmental samples.


Outcome of latissimus dorsi transfer for irreparable rotator cuff tears.
The aim of this retrospective study was to assess the mid- and long-term functional and radiological results following latissimus dorsi transfer for symptomatic irreparable tears of the supra- and infraspinatus tendons (postero-superior cuff tears). Twenty-six shoulders with an irreparable posterosuperior rotator cuff tear were assessed preoperatively and after latissimus dorsi transfer, using the Constant score and standard radiographs to determine the degree of osteoarthritis and to measure the acromio-humeral distance. After a minimal follow-up of one year (range: 13 to 124 months) we observed a significant increase in Constant score from 39 to 60 points at the time of the last follow-up (p < 0.00001). Eighty-five percent of the patients were satisfied or very satisfied with the result and would undergo the same surgery again. An increase in the grade of gleno-humeral osteoarthritis was noted in 38.5% of the operated shoulders, and this was associated with a lower Constant score. We noted a decrease in acromio-humeral distance, indicating further proximalisation of the humeral head, but this was not significant (p = 0.049).


In vivo estimation of the flow-driven adiabatic inversion efficiency for continuous arterial spin labeling: a method using phase contrast magnetic resonance angiography.
The accurate quantification of perfusion with arterial spin labeling (ASL) requires consideration of a number of factors, including the efficiency of the inversion and control pulses used for spin labeling. In this study the effects of spin velocity on continuous ASL efficiency when using the amplitude modulated control strategy were investigated using simulations of the Bloch equations. The inversion efficiency was determined in vivo by combining the simulations with phase-contrast velocity mapping data acquired at the level of the tagging plane. Using this novel method, an average inversion efficiency of 69% was calculated for a group of 28 subjects, in good agreement with experimental data reported previously. There was, however, a large range in inversion efficiency measured across the subject group (50-76%), indicating that the velocity dependence of the amplitude modulated control efficiency may introduce additional variability into the perfusion calculations if not properly taken into account.


Characteristics of human T-lymphotropic virus type-1 (HTLV-1)-infected cell line MT-2, which is not killed by a natural killer cell line NK-92 but is killed by lymphokine-activated killer cells.
Natural killer (NK) cell-mediated cytolysis (NK-lysis) is triggered by costimulatory signals of adhesion molecules and is downregulated by negative signals of killer cell inhibitory receptors (KIRs). Recently, a NK cell line, NK-92, was established. This cell line can kill several tumor cells, which possess adhesion molecules CD54 and CD102. However, the NK-92 cannot kill a human T-lymphotropic virus type 1 (HTLV-1)-infected cell line, MT-2, although lymphokine-activated killer (LAK) cells can kill MT-2. In this report we investigated the reason for LAK sensitivity but NK-92 resistance of the MT-2. The MT-2 highly expressed CD54 and CD102, suggesting that the costimulatory signals may be intact. Then we tested the responsibility of the negative signals by determining HLA type of the MT-2 and KIRs of the effector cells. The MT-2 expressed HLA-A24, B40, B51, Cw3, and HLA-G. The NK-92 did not express KIR2DL1, KIR2DL2,3, nor KIR3DL1, but 24% of the cells weakly expressed CD94. The blocking tests against these HLA class I molecules and KIRs did not restore the NK-92 resistance, although blocking against HLA-G slightly increased its lysis. Finally, in order to eliminate the class I molecules from the cell surface, we treated the MT-2 using a buffered citric acid solution (pH 3.8). By using this treatment, the expression of class I molecules and HTLV-1 antigen decreased, and then the MT-2 was killed by the NK-92. These findings suggest that an aberrant class I molecule of the MT-2 transferred a negative signal to the NK-92 and induced the NK-92 resistance. It remains to be elucidated whether or not the HTLV-1 infection contributed to the alteration of the class I molecule.


Optimising testing strategies for classification of human health and environmental hazards - A proof-of-concept study.
This paper outlines a new concept to optimise testing strategies for improving the efficiency of chemical testing for hazard-based risk management. While chemical classification based on standard checklists of information triggers risk management measures, the link is not one-to-one. Toxicity testing may be performed with no impact on the safe use of chemicals . Each hazard class and category is not assigned a unique pictogram and for the purpose of this proof-of-concept study, the level of concern for a chemical for the population and the environment is simplistically considered to be reflected by the hazard pictograms. Using active substances in biocides and plant protection products as a dataset, three testing strategies were built with the boundary condition that an optimal approach must indicate a given level of concern while requiring less testing (strategy B), prioritising new approach methodologies (strategy C) or combining the two considerations (strategy D). The implementation of the strategies B and D reduced the number of tests performed by 6.0% and 8.8%, respectively, while strategy C relied the least on in vivo methods. The intentionally simplistic approach to optimised testing strategies presented here could be used beyond the assessment of biocides and plant protection products to gain efficiencies in the safety assessment of other chemical groups, saving animals and making regulatory testing more time- and cost-efficient.


Understanding the standard of care in the treatment of type 2 diabetes in China: results from a national survey.
Given the pace with which standards of care have changed, timely assessment of their impact on routine clinical practice and patient outcomes is needed. In coordination with the Chinese Diabetes Society (CDS), we developed a quantitative survey to explore the implementation of standards of care for type 2 diabetes (T2D) in China. A national online survey of physicians involved in the management of T2D in China was conducted over a 4-week period in 2012. Completed responses were obtained from 1 028 physicians. Participants responded to 52 questions designed to capture information relating to their demographic and clinical practice profiles. The questionnaire was divided into three sections: basic information, diagnosis practices and screening methods on main complications, and treatment and control practices. The questionnaire was developed in conjunction with the CDS. Overall, 83% of surveyed physicians were at least "aware" of the CDS guidelines on standards of care for T2D. Level of awareness was directly related to hospital grade, specialty, geographic location, professional rank and participation in CDS training. The 2-hour oral glucose tolerance test was reported as the most ever-used approach across all three hospital grades and physician specialties, with a usage rate of 97%. Respondents selected their choice of primary treatment for newly diagnosed T2D patients. Just over half (52%) indicated the use of oral anti-diabetic drugs (OAD) monotherapy, in line with CDS recommendations. However, OAD use varied considerably between different regions and city tiers. Despite hemoglobin A1c being defined as the gold standard for glucose control, it was not universally measured, with more physicians indicating routine use of glucose before fasting and glucose non-fasting. The standards-of-care analysis has provided important insights into the current management of T2D among physicians in China across different geographical regions, hospital grades, specialties, professional statuses, and levels of CDS guideline awareness and training.


Epidemiology of tobacco use among Lumbee Indians in North Carolina.
Little is known regarding tobacco use among the Lumbee Indians in southeastern North Carolina, despite high prevalence of use and ties to tobacco-related agriculture. This report describes current and early childhood tobacco use in this population. A cross-sectional telephone survey of 400 adult Lumbee Indians was done in Pembroke, Robeson County, NC. Information was collected on demographics, tobacco use, knowledge and practices related to tobacco agriculture, and ceremonial tobacco use. 17.8% and 18.2% of the sample reported current and former smokeless tobacco (ST) use, and 26% and 19.5% reported current and former cigarette (CG) use, respectively. 17.3% reported ever use of both CG and ST. Current ST use was associated with older age, childhood involvement in tobacco-related agriculture, and less education. Current CG use was associated with younger age, male sex, less education, having never been married, infrequent church attendance, and fewer close friends or relatives. Early initiation of ST and CG use was more common among women, while early initiation of CG use was more common among persons who were younger and had lower levels of education. Current ST use is unusually common among Lumbee adults, while CG use reflects rates found in other populations. These data show different patterns of CG use and ST use, and suggest that strategies for tobacco use cessation must target each specific product.


Determination of atenolol by the micelle-stabilized room-temperature phosphorescence methodology.
A micellar-stabilized room-temperature phosphorescence (MS-RTP) method for the determination of atenolol has been developed in micellar solutions of sodium dodecylsulphate (SDS) in the presence of thallium(I) as a heavy atom and sodium sulphite as an oxygen scavenger. The effects of thallium(I) nitrate, SDS and sodium sulphite concentrations on atenolol MS-RTP intensity were studied. Optimized conditions to obtain maximum sensitivity were 0.015 mol/L thallium(I) nitrate, 0.1 mol/L SDS and 0.0075 mol/L sodium sulphite. The maximum phosphorescence signal was completely developed in 10 min and the intensity was measured at lambda(ex) = 272 nm and lambda(em) = 412 nm. The linear range of application obtained was 2.01-16.00 microg/mL. The detection limit estimated from the least-squares regression analysis was 0.86 microg/mL and the relative standard deviation of 10 replicates was 1.7%. The proposed method was applied to the determination of atenolol in a pharmaceutical formulation. The quantitation was carried out by means of standard calibration, standard-additions calibration and Youden calibration. These three experiments were necessary to evaluate the presence of constant and proportional errors due to the matrix.


An investigation of the benefits of Aquacel Hydrofibre wound dressing.
Aquacel wound dressing, produced by ConvaTec, uses the main ingredient of the hydrocolloid dressing in a new way to produce a hydrofibre dressing. Aquacel is designed for use in moderate to heavily exuding wounds as it absorbs exudate directly into its fibres. It has been shown to be effective in pressure sores, leg ulcers and surgical wounds, producing warm, moist, local wound conditions for optimum wound healing. Aquacel can lock exudate away thus protecting the surrounding skin.


Expression of miR-29 and STAT3 in osteosarcoma and its effect on proliferation regulation of osteosarcoma cells.
STAT3 has been shown to be involved in the occurrence, progression, and resistance of various tumors. The abnormal expression of miR-29 is associated with the pathogenesis of osteosarcoma. The bioinformatics analysis showed a targeting relationship between miR-29 and STAT3 3'-UTR. This study investigated whether miR-29 regulates the STAT3 expression and affects the proliferation and apoptosis of osteosarcoma cells. The tumor tissues of osteosarcoma patients were collected, and the adjacent tissues were used as controls to detect the expression of miR-29 and STAT3. The Dual-Luciferase Gene Reporter Assay validated the regulatory relationship between miR-29 and STAT3. The expression of miR-29 and STAT3 in normal osteoblasts hFOB1.19, osteosarcoma SJSA-1, and MG-63 was measured. SJSA-1 cells were divided into miR-NC group and miR-29 mimic group. Cell apoptosis and proliferation were detected by flow cytometry. Compared with adjacent tissues, miR-29 expression was decreased, and STAT3 expression was increased in osteosarcoma. There was a targeted regulation relationship between miR-29 and STAT3. Compared with hFOB1.19 cells, miR-29 expression in osteosarcoma SJSA-1 and MG-63 cells was decreased, with increased STAT3 expression. The transfection of miR-29 mimic significantly decreased the expression of STAT3 and p-STAT3 in SJSA-1 cells, inhibited cell proliferation, and increased cell apoptosis. Decreased miR-29 expression plays a role in the increase of the STAT3 expression and in the promotion of the pathogenesis of osteosarcoma. Increasing the expression of miR-29 can inhibit the proliferation of osteosarcoma cells and promote apoptosis by decreasing STAT3 expression.


Gene panel screening for insight towards breast cancer susceptibility in different ethnicities.
African American breast cancer genetics is less understood compared to European American breast cancer susceptibility. Despite the many advantages of gene panel screening, studies investigating African American inherited breast cancer risk and comparing variant contributions between ethnicities are infrequent. Thus, 97 breast cancer-affected individuals of African and European descent from the Alabama Hereditary Cancer Cohort were screened using the research-based gene-panel, B.O.P. (Breast, Ovarian, and Prostate cancer). Upon sequencing and bioinformatic processing, rare coding variants in 14 cancer susceptibility genes were categorized according to the American College of Medical Genetics guidelines and compared between ethnicities. Overall, 107 different variants were identified, the majority of which were benign/likely benign. A pathogenic/likely pathogenic variant was detected in 8.6% and 6.5% of African American and European American cases, respectively, which was not statistically significant. However, African Americans were more likely to have at least one variant of uncertain significance (VUS; p-value 0.006); they also had significantly more VUSs in BRCA1/2 compared to European Americans (p-value 0.015). Additionally, 51.4% of African Americans and 32.3% of European Americans harbored multiple rare variants, and African Americans were more likely to have at least one VUS and one benign/likely benign variant (p-value 0.032), as well as multiple benign/likely benign variants (p-value 0.089). Moreover, of the 15 variants detected in multiple breast cancer cases, ATM c.2289T>C (p.F763L), a VUS, along with two likely benign variants, BRCA2 c.2926_2927delinsAT (p.S976I) and RAD51D c.251T>A (p.L84H), were determined to be associated with African American breast cancer risk when compared to ethnic-specific controls. Ultimately, B.O.P. screening provides essential insight towards the variant contributions in clinically relevant cancer susceptibility genes and differences between ethnicities, stressing the need for future research to elucidate inherited breast cancer risk.