Assessing the effect of zooprophylaxis on zoonotic cutaneous leishmaniasis transmission: a system dynamics approach.
Capturing or diverting the disease carrying vector from humans can reduce the transmission of vector borne diseases such as leishmaniasis. The use of animals that act as dead-end hosts to relieve the vector (sandfly) bites on humans is called zooprophylaxis. However, as the number of blood meal providers especially domestic animals increases, the sandflies enhanced availability of blood meals will improve its number and survival, thereby countering the impact of diverting bites from humans. Thus, the transmission model exhibits the structure of a feedback loop characterizing complex dynamic systems. In order to rigorously assess the effect of zooprophylaxis, we propose a system dynamic model for zoonotic cutaneous leishmaniasis transmission with 3 blood-meal hosts: domestic animals, humans, and a reservoir (rodents). In this context, a simulation study of the proposed model with a follow-up period of 1000 days was performed. We explored how perturbations in the parameters characterizing the transmission, essentially the vector biting rates and the size of the domestic animal population, affect the zooprophylaxis outcome. The results show that the basic reproductive number R0 and the disease incidence in humans are decreasing function of the relative size of the domestic animal population. The speed of this decrease depends also on the vector biting rates of the different mammal species. The key factors influencing the magnitude of zooprophylaxis are: the sizes of the vector, rodent, and domestic animal populations, as well as, the biting rates which incorporate relative attraction and accessibility of the vectors to the mammalian populations.


Coagulation-fibrinolysis changes during off-pump bypass: effect of two heparin doses.
To date, no study has tested the effect of different heparin dosages on the hemostatic changes during off-pump coronary artery bypass graft (OPCABG) surgery, and a wide variety of empirical anticoagulation protocols are being applied. We tested the effect of two different heparin dosages on the activation of the hemostatic system in patients undergoing OPCABG procedures. Forty-two patients eligible for OPCABG procedures were assigned in a randomized fashion to low-dose heparin (150 IU/kg) or high-dose heparin (300 IU/kg). Prothrombin fragment 1+2, plasmin/alpha(2)-plasmin inhibitor complex, D-dimer, soluble tissue factor, tissue factor pathway inhibitor, total thrombin activatable fibrinolysis inhibitor (TAFI), and activated TAFIa were assayed by specific enzyme-linked immunosorbent assays at six different timepoints, before, during, and after surgery. Platelet function was evaluated by means of an in vitro bleeding time test, platelet function analyzer-100. The OPCABG surgery was accompanied by significant changes of all plasma biomarkers, indicative of systemic activation of coagulation and fibrinolysis. A significant increase in circulating TAFIa was detected perioperatively and postoperatively, and multiple regression analysis indicated that prothrombin F1+2 but not plasmin/alpha(2)-antiplasmin complex was independently associated with TAFIa level. Platelet function analyzer-100 values did not change significantly after OPCABG. All hemostatic changes were similar in the two heparin groups, even perioperatively, when the difference in anticoagulation was maximal. Both early and late hemostatic changes, including TAFI activation, are similarly affected in the low-dose and high-dose heparin groups, suggesting that the increase in heparin dosage is not accompanied by a better control of clotting activation during OPCABG surgery.


Comparative study of atherosclerotic parameters in Mongolian and Japanese patients with hypertension and diabetes mellitus.
Cardiovascular disease is becoming increasingly more problematic in Mongolia. The cardioankle vascular index (CAVI) and circulating C-reactive protein (CRP) are new atherosclerosis-related parameters, but no comparative studies of atherosclerotic parameters including CAVI and CRP are available between Mongolian and Japanese populations, such as disease populations of hypertension (HT) and diabetes mellitus (DM). Our study objective was to examine atherosclerotic profiles in HT and DM patients in both countries. From a hospital-based population, 156 Mongolian outpatients with HT and DM (men: 46%, mean age: 57.1 years) and 156 age- and sex-matched Japanese outpatients with HT and DM (men: 46%, age: 57.7) were recruited. Body mass index (BMI), heart rate (HR), blood pressure (BP), pulse pressure (PP), ankle-brachial index (ABI), ultrasonographic carotid intima-media thickness (IMT), blood total cholesterol (T-Cho), glucose, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were measured, in addition to CAVI and CRP. The levels of BMI, HR, BP, PP, insulin and IMT were significantly higher and T-Cho and glucose were significantly lower in the Mongolian patients in comparison to the Japanese patients. Particularly, the levels of CAVI (mean+/-SD) (8.1+/-1.1 vs. 8.8+/-1.2) and CRP(median[interquartile range])(0.05[0.03-0.12]vs. 0.19[0.09-0.42]mg/dL)were significantly higher in Mongolian than Japanese patients. These significant differences remained unchanged, even after taking into account multiple variables, including BP and HOMA-IR. In addition, except for CAVI in the subgroup of DM, generally similar trends regarding atherosclerotic parameters were seen in the subgroup by sex and disease (HT, DM and HT plus DM). These findings suggest that Mongolian patients with HT and DM may be at higher risk for cardiovascular disease than Japanese patients.


[The influence of clinical presentation and metabolic control of insulin dependent diabetes in the evolution of residual insulin secretion. A prospective study at five years].
To study the influence of clinical, metabolic and immunological parameters during the first years of the evolution of insulin-dependent diabetes mellitus (IDDM) on the long-term residual insulin secretion (IS). 186 IDDM subjects diagnosed from 1986 to 1993 were included; 135 subjects have completed a two year follow-up, and 57 have completed a five year follow-up. The influence of individual characteristics at diagnosis (age, sex, clinical presentation, islet-cell antibodies) and during the first two years of follow-up (IS, metabolic control) on IS at five years was evaluated by multiple linear regression. Differences between groups were evaluated by non-parametric tests. 18 patients had a significant insulin secretion at five years (post-glucagon C-peptide > or = 0.15 nmol/l). They showed minor significant differences in sex (77.7 vs 48.7% of males, p = 0.03), duration of symptoms (12.9 vs 7.2 weeks, p = 0.01), ketoacidosis at diagnosis (23.3 vs 46.1%, p = 0.07) and ICA positivity at diagnosis (41.1 vs 69.4%, p = 0.05). They also had a better metabolic control (8.8 vs 10.8% of HbA1, p < 0.001) with lss insulin (0.48 vs 0.71 Ul/kg, p < 0.001) during the first two years of evolution. Initial IS was similar, but differences became significant at 6 months. In the multivariate analysis, only metabolic control during the second year of evolution (p = 0.008), ketoacidosis at diagnosis (p = 0.026) and sex (p = 0.026) had an independent influence on IS at five years. A more intensified therapeutic approach introduced in 1990 induced a better metabolic control and higher IS during the first years of follow-up. The absence of ketoacidosis at diagnosis and a good metabolic control during the first two years can have a positive influence in the long-term preservation of IS in IDDM patients.


NanoBRET: The Bright Future of Proximity-Based Assays.
Bioluminescence resonance energy transfer (BRET) is a biophysical technique used to monitor proximity within live cells. BRET exploits the naturally occurring phenomenon of dipole-dipole energy transfer from a donor enzyme (luciferase) to an acceptor fluorophore following enzyme-mediated oxidation of a substrate. This results in production of a quantifiable signal that denotes proximity between proteins and/or molecules tagged with complementary luciferase and fluorophore partners. BRET assays have been used to observe an array of biological functions including ligand binding, intracellular signaling, receptor-receptor proximity, and receptor trafficking, however, BRET assays can theoretically be used to monitor the proximity of any protein or molecule for which appropriate fusion constructs and/or fluorophore conjugates can be produced. Over the years, new luciferases and approaches have been developed that have increased the potential applications for BRET assays. In particular, the development of the small, bright and stable Nanoluciferase (NanoLuc; Nluc) and its use in NanoBRET has vastly broadened the potential applications of BRET assays. These advances have exciting potential to produce new experimental methods to monitor protein-protein interactions (PPIs), protein-ligand interactions, and/or molecular proximity. In addition to NanoBRET, Nluc has also been exploited to produce NanoBiT technology, which further broadens the scope of BRET to monitor biological function when NanoBiT is combined with an acceptor. BRET has proved to be a powerful tool for monitoring proximity and interaction, and these recent advances further strengthen its utility for a range of applications.


Fabrication of syntactic foam fillers via integrated on/off-chip microfluidic methods for optimized geopolymer composites.
To meet the evolving requirements of material designability, sustainability, and eco-friendliness, the development of syntactic foams puts great emphasis on filler optimization and matrix selection. Here, we present a novel microfluidic expansion coupled with the thermal contraction method to improve the fabrication of syntactic foam fillers (SFFs), highlighted by the independently regulated parameters in contrast to the hydrodynamic regulation approach. The eccentricity of droplets can be reduced via osmotic swelling under a hypotonic circumstance and further preserved through real-time UV polymerization. The eccentricity of shrunken SFFs after heat treatment is found to inherit the regulated configurations of droplets and this homogeneity difference of shell thickness can result in the mechanical performance deviation. Then, we choose greener material, geopolymer, as the binder matrix and prepare geopolymer syntactic foams (GSFs) by mold casting. The inclusion of SFFs has increased the atomic volume ratio of Si : Al in the matrix, thereby forming a strong interfacial bonding. The compressive yield strength of GSFs is inversely proportional to the volume fraction of SFFs, and the specimens after thermal exposure can still maintain their shape integrity and exhibit similar mechanical performance even with the formation of cracks. Moreover, the fire-resistant performance of GSFs has been visually validated by the combustion comparison experiment, characterized as flame retardancy, smoke-free, and basically intact morphology, which should give insights into the design and fabrication of functional composites.


Risk assessment and genetic testing for ovarian cancer.
Prevention of ovarian cancer starts with identifying women at high risk for this deadly disease. Once identified, these women can be offered risk-reducing options such as oral contraceptives and bilateral salpingo-oophorectomy. In this review, strategies for identifying high-risk individuals and the clinical utility of genetic testing for BRCA1 and BRCA2 will be discussed. To offer potentially life-saving interventions for at-risk family members, we propose that every woman newly diagnosed with ovarian cancer be offered genetic testing for BRCA1 and BRCA2 genes because mutations in these genes are the strongest known predictors of ovarian cancer risk.


Mechanical properties of spider dragline silk: humidity, hysteresis, and relaxation.
Spider silk is well-known for its outstanding mechanical properties. However, there is a significant variation of these properties in literature and studies analyzing large numbers of silk samples to explain these variations are still lacking. To fill this gap, the following work examines the mechanical properties of major ampullate silk based on a large ensemble of threads from Nephila clavipes and Nephila senegalensis. In addition, the effect of relative humidity (RH) on the mechanical properties was quantified. The large effect of RH on the mechanical properties makes it plausible that the variation in the literature values can to a large extent be attributed to changes in RH. Spider silk's most remarkable property-its high tenacity-remains unchanged. In addition, this work also includes hysteresis as well as relaxation measurements. It is found that the relaxation process is well described by a stretched exponential decay.


GLCCI1 and STIP1 variants are associated with asthma susceptibility and inhaled corticosteroid response in a Tunisian population.
Objective: Pharmacogenetic studies have recognized specific genes that highly correlate with response to inhaled corticosteroids (ICS) treatment in asthma patients. Among the genes identified, we selected glucocorticoid-induced transcript 1 (GLCCI1) and stress-induced phosphoprotein 1 (STIP1) to evaluate the impact of these gene polymorphisms on ICS treatment response in Tunisian asthmatics.Methods: We analyzed four single nucleotide polymorphisms (SNPs): two in GLCCI1 (rs37972 and rs37973), and two in STIP1 (rs2236647 and rs2236648), which are genes associated with susceptibility to asthma and response to ICS in a Tunisian cohort. The SNPs were genotyped using reverse transcriptase polymerase chain reaction (RT-PCR) techniques.Results: This case-control study consisted of 230 adult asthmatic patients and 236 healthy subjects. Seventy-five asthmatics were selected and followed through 12 weeks of routine treatment. The T allele rs2236648 in STIP1 was associated with allergic asthma (OR = 0.38, 95%CI = 0.20-0.69, p = 0.001). The rs37972 and rs37973 of GLCCI1 were associated with a higher risk of asthma (p < 0.001). The T allele rs37972 and G allele rs37973 were correlated with a strong risk for developing severe asthma (p < 0.001). Asthma patients carrying the rs37973 GG genotype had less improvement in the forced expiratory volume in one second (FEV1) than those with the AA or AG genotypes after 12 weeks of treatment (p < 0.001). Also, the G allele of rs37973 was associated with worse response to ICS after 12 weeks of treatment (p < 0.001).Conclusion: The rs37972 and rs37973 polymorphisms can serve as potential asthma risk biomarkers in a Tunisian population.


Association between Elemental Content and Fruit Ripening in rin and Normal Tomatoes.
Analysis of Ca and other inorganic ions in the pericarp of rin, a nonripening mutant, and normal tomato (Lycopersicon esculentum Mill) fruits revealed significant differences in their accumulations at advanced stages of fruit development. During early stages of fruit development, soluble Ca was higher in Rutgers and there were no detectable changes in the accumulation patterns of the other inorganic ions. In the mutant rin, bound Ca continued to increase with age and it was twice as high as compared to earlier stages. In the normal tomato, bound Ca decreased about 3-fold at later stages of development. Mg and Mn also showed some changes similar to Ca. K continued to increase with age and the mutant rin had lower levels than Rutgers throughout development. Other ions such as P, Zn, Cu, and Co were similar in the mutant and normal fruits. These results are interpreted as indicating that high levels of bound divalent cations in the mutant rin may be associated with an altered membrane and cell wall and play a role in fruit ripening.


Autoimmunity in narcolepsy.
Summarize the recent findings in narcolepsy focusing on the environmental and genetic risk factors in disease development. Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Recent studies suggest both humoral and cellular immune responses in the disease development. Narcolepsy is a severe sleep disorder, in which neurons producing orexin/hypocretin in the hypothalamus are destroyed. The core symptoms of narcolepsy are debilitating, extreme sleepiness, cataplexy, and abnormalities in the structure of sleep. Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Importantly, the highest environmental risk is seen with influenza-A infection and immunization. However, how the cells are destroyed is currently unknown. In this review we summarize the disease symptoms, and focus on the immunological findings in narcolepsy. We also discuss the environmental and genetic risk factors as well as propose a model for disease development.


Teacher training and HIV/AIDS prevention in West Africa: regression discontinuity design evidence from the Cameroon.
We assess the impact on teenage childbearing as well as student knowledge, attitudes, and behavior of a typical HIV/AIDS teacher training program in the Cameroon. Applying a regression discontinuity design identification strategy based on the key administrative criterion that determined program deployment, we find that 15-17 year old girls in teacher training schools are between 7 and 10 percentage points less likely to have started childbearing, an objective proxy for the incidence of unprotected sex. They are also significantly more likely to have used a condom during their last sexual intercourse. For 12-13 year old girls, the likelihood of self-reported abstinence and condom use is also significantly higher in treated schools, while the likelihood of having multiple partners is significantly lower.


Public health on the railroad: William Freeman Snow and the California Sanitation Exhibit.
This paper describes the California Sanitation Exhibit, a railroad car outfitted for instruction in public health that toured California in 1909 and 1910. The sanitation exhibit used display models, photographs, and lectures to educate the public about tuberculosis and other infectious diseases, waste contamination, and the dangers of bad milk. The success of the exhibit, which reached 5% of the state's population, resulted in the appointment of its creator, William Freeman Snow, as secretary of the California State Board of Health.


Straight and curved conformations of FtsZ are regulated by GTP hydrolysis.
FtsZ assembles in vitro into protofilaments that can adopt two conformations-the straight conformation, which can assemble further into two-dimensional protofilament sheets, and the curved conformation, which forms minirings about 23 nm in diameter. Here, we describe the structure of FtsZ tubes, which are a variation of the curved conformation. In the tube the curved protofilament forms a shallow helix with a diameter of 23 nm and a pitch of 18 or 24 degrees. We suggest that this shallow helix is the relaxed structure of the curved protofilament in solution. We provide evidence that GTP favors the straight conformation while GDP favors the curved conformation. In particular, exclusively straight protofilaments and protofilament sheets are assembled in GMPCPP, a nonhydrolyzable GTP analog, or in GTP following chelation of Mg, which blocks GTP hydrolysis. Assembly in GDP produces exclusively tubes. The transition from straight protofilaments to the curved conformation may provide a mechanism whereby the energy of GTP hydrolysis is used to generate force for the constriction of the FtsZ ring in cell division.


Fate of silica nanoparticles in simulated primary wastewater treatment.
Through novel application of small-angle neutron scattering, we examined the fate of silica nanoparticles (SiO(2)NPs) during simulated primary wastewater treatment, by measuring, in real time, the colloidal behavior of SiO(2)NPs in wastewater (sewage). We examined the effects of surface functionality on SiO(2)NP fate in wastewater, by comparing both unfunctionalized (uncoated or "bare") SiO(2)NPs and SiO(2)NPs functionalized with a thin coating of a nonionic surfactant (Tween 20), which is widely used in personal care and household product formulations containing engineered oxide nanoparticles. Our results show new evidence that the surface functionality of SiO(2)NPs plays a crucial role in their flocculation and sedimentation behavior in wastewater, and thus the likely efficacy of their removal from the effluent stream during primary wastewater treatment. Uncoated SiO(2)NPs did not flocculate in wastewater over typical residence times for primary treatment. Conversely, surface-functionalized (Tween-coated) SiO(2)NPs underwent rapid flocculation in wastewater. Our results show that the surface-functionalized SiO(2)NPs are likely to be removed by sedimentation to sewage sludge (typically recycled to land), whereas uncoated SiO(2)NPs will continue through the effluent stream. While nanoparticle design is driven by use purpose, this study shows new potential for exploiting surface functionalization of nanoparticles to modify their environmental pathways.


The impact of heat islands on mortality in Paris during the August 2003 heat wave.
Heat waves have a drastic impact on urban populations, which could increase with climate change. We evaluated new indicators of elderly people's exposure to heat in Paris, from a public health prevention perspective, using satellite thermal images. We used a time series of 61 images from the satellites of the National Oceanic and Atmospheric Administration's (NOAA) Advanced Very High Resolution Radiometer (AVHRR) taken from 1 to 13 August 2003 to produce thermal indicators of minimum, maximum, and mean surface temperatures and diurnal temperature amplitude, with different lags between the meteorological data and the health impact. Health data came from a case-control study involving 241 people ≥ 65 years of age who died in the city of Paris or the nearby suburban area of Val-de-Marne during the August 2003 heat wave, and 241 controls who were matched to cases on age, sex, and residential zone. For each person, we integrated the thermal indicators in a conditional logistic regression model, adjusted for age and other potential confounders. We computed odds ratios (ORs) comparing the 90th and 50th percentiles of the temperature differences between cases and controls for various indicators. Mortality risk was significantly associated with exposure for two indicators: minimum temperatures averaged for 1-13 August [for a 0.41°C increase, OR = 2.17; 95% confidence interval (CI): 1.14, 4.16] and minimum temperature averaged on the day of death and the 6 preceding days (for a 0.51°C increase: OR = 2.24; 95% CI: 1.03, 4.87). Our results support the influence of night temperatures on the health impact of heat waves in urban areas. Urban heat exposure indicators based on satellite imagery have the potential to identify areas with higher risk of death, which could inform intervention decisions by key stakeholders.


Amphipathic Peptides Impede Lipid Domain Fusion in Phase-Separated Membranes.
Cell membranes are heterogeneous in lipid composition which leads to the phase separation with the formation of nanoscopic liquid-ordered domains, also called rafts. There are multiple cell processes whereby the clustering of these domains into a larger one might be involved, which is responsible for such important processes as signal transduction, polarized sorting, or immune response. Currently, antimicrobial amphipathic peptides are considered promising antimicrobial, antiviral, and anticancer therapeutic agents. Here, within the framework of the classical theory of elasticity adapted for lipid membranes, we investigate how the presence of the peptides in a phase-separated membrane influences the fusion of the domains. We show that the peptides tend to occupy the boundaries of liquid-ordered domains and significantly increase the energy barrier of the domain-domain fusion, which might lead to misregulation of raft clustering and adverse consequences for normal cell processes.


The study of the influence of pH on the structural and spectroscopic properties of nanocrystalline Eu3+ ion-doped yttrium orthovanadate.
In this study, it has been presented the influence of pH conditions on the evolution of the size, morphology and spectroscopic properties of yttrium orthovanadate during synthesis. A thorough research on the spectroscopic properties was performed. A series of highly crystalline 1 mol% Eu3+:YVO4 has been synthesized via the co-precipitation method. In addition, to improve the crystallinity, the materials were heat-treated at 800 °C, and the structural and morphological properties of the particles were studied using XRD (X-ray powder diffraction) and SEM (Scanning Electron Microscopy) techniques. In order to investigate the spectroscopic properties of 1 mol% Eu3+:YVO4, emission spectra and luminescence kinetics were measured. It was found that alkaline pH manifests in smaller particles compared to acidic pH conditions. In addition, superior spectroscopic properties were observed in materials obtained in alkaline pH.


Conformational determinants of the activity of antiproliferative factor glycopeptide.
The antiproliferative factor (APF) involved in interstitial cystitis is a glycosylated nonapeptide (TVPAAVVVA) containing a sialylated core 1 α-O-disaccharide linked to the N-terminal threonine. The chemical structure of APF was deduced using spectroscopic techniques and confirmed using total synthesis. The synthetic APF provided a platform to study amino acid modifications and their effect on APF activity, based on which a structure-activity relationship (SAR) for APF activity was previously proposed. However, this SAR model could not explain the change in activity associated with minor alterations in the peptide sequence. Presented is computational analysis of 14 APF derivatives to identify structural trends from which a more detailed SAR is obtained. The APF activity is found to be dictated by the close interplay between carbohydrate-peptide and peptide-peptide interactions. The former involves hydrogen bond and hydrophobic interactions, and the latter is dominated by hydrophobic interactions. The highly flexible hydrophobic peptide adopts collapsed conformations separated by low energy barriers. APF activity correlates with hydrophobic clustering associated with amino acids 4A, 6V, and 8V. Peptide conformations are highly sensitive to single point mutations, which explain the experimental trends. The presented SAR will act as a guide for lead optimization of more potent APF analogues of potential therapeutic utility.


Management of acute pediatric asthma.
Pediatric asthma prevalence, morbidity, and severity are increasing. Direct costs associated with providing emergency department and inpatient care account for more than 40% of overall dollars spent for this disease in the United States. Physicians in many health care settings may be required to treat a child in severe respiratory distress caused by acute asthma. This article reviews the pathophysiology, evaluation, and treatment of severe asthma exacerbations, or status asthmaticus.


Indonesian midwives' perspectives on changes in the provision of maternity care during the COVID-19 pandemic: A qualitative study.
To explore how COVID-19 influenced the provision of high-quality maternity care in Indonesia. A qualitative descriptive study using in-depth interviews was undertaken. Thematic analysis was used to analyse data, and behaviour change frameworks (Theoretical Domain Framework (TDF) and Capability, Opportunity, and Motivation (COM-B)) were used to identify and map facilitators and barriers influencing maternity care provision during the COVID-19 pandemic. Fifteen midwives working in community maternity care facilities in Surabaya and Mataram, Indonesia were included. Surabaya is in western Indonesia, with around 56,000 births per year and a population of around 3 million. Mataram is in eastern Indonesia, with around 7,000 births per year and a population of around 500,000. The main changes to maternity care provision during the COVID-19 pandemic were reduced frequency of antenatal and postpartum care visits, reduced support for women, including unavailability of maternity care and reduced number of antenatal care and labour companions, changes in location of provision of care, and public health changes related to COVID-19. The main factors influencing the provision of high-quality maternity care during the COVID-19 pandemic were behavioural regulation, professional role and identity, and environmental context and resources. Maternity care provision underwent substantial changes during the COVID-19 pandemic in Indonesia. Findings from this study can contribute to better understanding of how maternity care provision changed during the pandemic, and how positive changes can be reinforced, and negative changes can be addressed.


The effects of large negative intrathoracic pressure on left ventricular function in patients with coronary artery disease.
Using first-pass radionuclide ventriculography, we evaluated the effects of decreases in intrathoracic pressure (Mueller maneuver [M] to -20 to -30 cm H2O) in 14 patients with five patients without coronary artery disease (CAD) and in 12 normal control subjects. In the patients with CAD, control ejection fraction was 0.53 +/- 0.06 (SEM) and control heart rate was 83 +/- 6 beats/min. These did not change during M. In the patients with CAD, control ejection fraction was 0.37 +/- 0.03 and heart rate was 82 +/- 7 beats/min. During M, heart rate did not change, but ejection fraction decreased to 0.33 +/- 0.33 (p less than 0.01). Examination of regional wall motion abnormalities showed akinesis of at least one myocardial segment in nine of 14 patients with CAD, but in none of the patients without CAD, nor in any of the 12 previously studied normal subjects (retrospectively analyzed). These data are consistent with the hypothesis that the Mueller maneuver acts to increase afterload placed on the left ventricle. Furthermore, in patients with CAD, the Mueller maneuver may have induced localized myocardial ischemia or unmasked areas of preexisting marginal function.


MicroRNA expression profiles in the management of papillary thyroid cancer.
Papillary thyroid cancer (PTC) is the major contributor to the dramatically increasing incidence of thyroid cancer. Low-risk PTC shows the most rapid rate of increase because of changing trends in neck imaging and the use of fine needle aspiration to investigate thyroid nodules. The need for a paradigm shift in the management of these patients, to provide personalized treatment and surveillance plans, has led to the focus on molecular biomarker research. MicroRNAs (miRNAs) compose a class of molecules with promising applications for every stage of PTC management, including diagnosis, prognosis, treatment, and surveillance. Although most of the miRNA studies are currently preclinical, given the rapid progress of scientific discovery, clinical trials will not be far away. Thyroid clinicians will be expected to have good insights into the current status of PTC-related molecular translational research. This article focuses on the potential roles of miRNA in PTC management in the context of contemporary recommended clinical practice.


Polymerase gamma disease through the ages.
The most common group of mitochondrial disease is due to mutations within the mitochondrial DNA polymerase, polymerase gamma 1 (POLG). This gene product is responsible for replication and repair of the small mitochondrial DNA genome. The structure-function relationship of this gene product produces a wide variety of diseases that at times, seems to defy the common perceptions of genetics. The unique features of mitochondrial physiology are in part responsible, but POLG structure and function add to the conundrum of how one gene product can demonstrate autosomal recessive and autosomal dominant transmission, while also being responsible for pharmacogenetic disease, and exhibiting strong gene-environment interactions. The wide spectrum of clinical manifestations of POLG disease can arise from infancy to old age. The modulation of clinical findings relate in part to the molecular architecture of the POLG protein. POLG has three distinct molecular domains: exonuclease, linker, and polymerase domains. Most of the mutations leading to dominant forms of POLG disease are located in the Polymerase domain. Mutations leading to recessive inheritance are distributed in all three domains of the gene. Environmental factors like valproic acid and infection can unmask POLG disease, causing it to occur earlier in life than when not exposed to these factors. Other drugs like nucleoside reverse transcriptase inhibitors can produce genotype-specific POLG pharmacogenetic disease. Our current state of POLG understanding cannot account for many features of POLG disease. There is no answer for why the same mutation can give rise to varying diseases, disease severity, and age of onset. We introduce the term Ecogenetics in the context these features of POLG disease, to emphasize the important interactions between genes and environment in determining the expression of mitochondrial disease. In this article, we identify some of the key features that will help the reader understand POLG pathophysiology. When possible, we also identify genotype-phenotype relationships, give clues for diagnosis, and summarize the major clinical phenotypes in the spectrum of POLG disease presenting from birth to old age.


Analyzing recent coronary heart disease mortality trends in Tunisia between 1997 and 2009.
In Tunisia, Cardiovascular Diseases are the leading causes of death (30%), 70% of those are coronary heart disease (CHD) deaths and population studies have demonstrated that major risk factor levels are increasing. To explain recent CHD trends in Tunisia between 1997 and 2009. Published and unpublished data were identified by extensive searches, complemented with specifically designed surveys. Data were integrated and analyzed using the previously validated IMPACT CHD policy model. Data items included: (i)number of CHD patients in specific groups (including acute coronary syndromes, congestive heart failure and chronic angina)(ii) uptake of specific medical and surgical treatments, and(iii) population trends in major cardiovascular risk factors (smoking, total cholesterol, systolic blood pressure (SBP), body mass index (BMI), diabetes and physical inactivity). CHD mortality rates increased by 11.8% for men and 23.8% for women, resulting in 680 additional CHD deaths in 2009 compared with the 1997 baseline, after adjusting for population change. Almost all (98%) of this rise was explained by risk factor increases, though men and women differed. A large rise in total cholesterol level in men (0.73 mmol/L) generated 440 additional deaths. In women, a fall (-0.43 mmol/L), apparently avoided about 95 deaths. For SBP a rise in men (4 mmHg) generated 270 additional deaths. In women, a 2 mmHg fall avoided 65 deaths. BMI and diabetes increased substantially resulting respectively in 105 and 75 additional deaths. Increased treatment uptake prevented about 450 deaths in 2009. The most important contributions came from secondary prevention following Acute Myocardial Infarction (AMI) (95 fewer deaths), initial AMI treatments (90), antihypertensive medications (80) and unstable angina (75). Recent trends in CHD mortality mainly reflected increases in major modifiable risk factors, notably SBP and cholesterol, BMI and diabetes. Current prevention strategies are mainly focused on treatments but should become more comprehensive.


Occult pneumonia: an unusual but perilous entity presenting with severe malnutrition and dehydrating diarrhoea.
A three-month old boy was admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh, with the problems of acute watery diarrhoea with some dehydration and suspected dyseletrolytaemia, severe malnutrition, and reduced activity. Occult pneumonia was added to the problem list after demonstration of radiologic consolidation in right upper lung, despite the lack of clinical signs, both on admission and after correction of dehydration. The problem list was further expanded to include bacteraemia due to Staphylococcus aureus when the blood culture report was available. Severely-malnourished children may not exhibit typical clinical signs of pneumonia, and the possibility of existence of such problems should be remembered in the assessment and provision of care to hospitalized young children with severe malnutrition.


[Idiopathic generalized epileptic syndromes of children].
The idiopathic generalized epilepsies of children form a neurobiological continuum which starts during the first years of life, until adolescence. In this group, infantile absence epilepsy may be considered to be the maximum expression of the idiopathic generalized epilepsies in this age group. Infantile absences have seen studied in animal models, in humans and genetically. We analyze the clinical and encephalographic characteristics of infantile absence epilepsies together with their prognosis and epidemiology. We also consider the palpebral myoclonias with absences and absences with perioral myoclonias. The generalized tonic-clonic seizures of childhood form an ill-defined epileptic syndrome, with very heterogeneous clinical and electroencephalographic characteristics. It seem important to be able to establish the precise diagnosis in these syndromes, since correct treatment depends on it.


Small-Angle X-ray Scattering Analysis of Colloidal Crystals and Replica Materials Made from l-Arginine-Stabilized Silica Nanoparticles.
Colloidal crystals made from sub-100 nm silica nanoparticles have provided a versatile platform for the template-assisted synthesis of three-dimensionally interconnected semiconducting, metallic, and magnetic replicas. However, the detailed structure of these materials has not yet been characterized. In this study, we investigated the structures of colloidal crystalline films and germanium replicas by scanning electron microscopy and small angle X-ray scattering. The structures of colloidal crystals made by evaporative assembly depends on the size of l-arginine-capped silica nanoparticles. Particles smaller than ∼31 nm diameter assemble into non-close-packed arrangements (bcc) whereas particles larger than 31 nm assemble into random close-packed structures with disordered hexagonal phase. Polycrystalline films of these materials retain their structures and long-range order upon infiltration at high temperature and pressure, and the structure is preserved in Ge replicas. The shear force during deposition and dispersity of silica nanoparticles contributes to the size-based variation in the structure and to the size of crystal domains in the colloidal crystal films.


New sternal puncture needle.
The needles most commonly used for obtaining bone marrow aspirates from the sternum are the Salah and Klima needles. They were designed in the 1930s, and except for the introduction of different kinds of stops and guards there has been no change in their basic structure and design. These instruments are small, do not fit properly in the operator's hand, and the lack of a T-bar handle often makes them difficult to manoeuvre; their introduction into the sternum by twisting or rotary movement of the hand can be cumbersome. To overcome all of these disadvantages an instrument was designed which is larger, provides better grip, and offers improved maneuverability. The stilette of this aspiration needle has a domed handle which rests snugly in the operator's hand and affords operator comfort, while the specially shaped large T-bar handle at the proximal end of the needle provides adequate and firm grip and also ensures precise control during the sternal puncture procedure.


Comparing the influences of age and disease on distortion in the clock drawing test in Japanese patients with schizophrenia.
The Clock Drawing Test (CDT) is commonly used for cognitive screening, but there are few studies that compare performance on the CDT among schizophrenic patients of different ages. The objective of this study was to investigate the influence of schizophrenia and aging on performance in the CDT. Schizophrenic patients (N = 244) and a comparison group (N = 875) were recruited as subjects. Freedman's CDT was completed by all subjects, and the influences of disease and aging on performance in the CDT were examined. Multiple comparisons of the CDT scores between patients and the comparison group and within three age subgroups (young: less than 40 years, middle aged: 40-59 years, elderly: more than 60 years) were performed. There was a significant interaction of diagnosis and age, and the education significantly influenced the total score for all CDT conditions. For almost all age subgroups of patients, individuals with schizophrenia had significantly lower scores on all the CDT conditions than did the comparison group subjects. For patients and the comparison group, the elderly subgroup performed significantly worse than the young and middle-aged subgroups on almost all conditions of the CDT. Qualitative analysis of the clocks drawn revealed that the number of CDT categories in which schizophrenic patients scored significantly lower than the comparison group tended to increase with aging across both groups. This study suggests that performance on the CDT was impaired not only by disease but also by aging. The study confirms that the CDT is sensitive enough to screen for cognitive impairments in schizophrenia.


Distinct association of the nuclear pore protein Nup153 with A- and B-type lamins.
The nuclear envelope (NE) is a double membrane physical barrier, which separates the nucleus from the cytoplasm. Underlying the NE are the nuclear lamins, which in combination with inner nuclear membrane proteins form the lamina. The lamina is crucial for maintaining the structural integrity of the nucleus and for positioning of nuclear pore complexes (NPCs) within the NE. The nucleoporin Nup153 has previously been reported to bind to B-type lamins. However, the specificity of this interaction is not well established. Here we show that Nup153 exhibits multiple binding sites for A- and B-type lamins. Using GST-pull down assays, we found that both the N-terminal domain of Nup153 and its C terminus associate with the Ig-fold domain of A- and B-type lamins. By employing purified Nup153 and lamin proteins in blot overlay assays we revealed that both the N-terminal and the C-terminal domain of Nup153 are directly interacting with the lamins. Moreover, we provide evidence that mutations in the lamin A Ig-fold domain selectively affect Nup153-binding, suggesting that Nup153 may play a role in lamin-associated diseases, known as laminopathies. Together our results indicate a far more intricate interplay between Nup153 and nuclear lamins than previously accepted.


Perioperative use of antibiotics in intra-abdominal surgical infections.
We created a questionnaire with the aim of evaluating surgeon compliance with the guidelines for antibiotic use in the perioperative period in intra-abdominal surgical infections. We discuss the problems emerging from non-adherence to these guidelines. In the questionnaire, we tried to correlate the type of intra-abdominal infection with: (1) Time of antibiotic administration commencement; (2) type of antibiotic(s) administered; (c) duration of antibiotic administration; and (4) modification of antibiotic type/duration of administration in the presence of factors increasing the risk of treatment failure. In order to collect and process the data more easily, the patients were divided into four groups-Group A: Community patients with intra-abdominal surgical infections and simple contamination of the peritoneal cavity according to the Surgical Infection Society (SIS) guidelines; Group B: Community patients with an intra-abdominal surgical infection evolving to secondary peritonitis per SIS guidelines; Group C: Community patients with an intra-abdominal surgical infection with a high risk of surgical site infection; and Group D: Patients with recent hospitalization or nosocomial or postoperative intra-abdominal infection. The questionnaire was sent to the directors of 43 surgical clinics in northern Greece, and 27 answered (63%). In 81.5% of the clinics (median 22; range 15-24), depending on the type of infection, empirical antibiotic treatment commenced preoperatively. In Group A, on average, 29.6% of the clinics (median 8; range 5-16) administer antibiotics for as long as 24 h, and 11.1% (median 3; range 1-10) use antibiotics not recommended in the SIS guidelines (e.g., third- and fourth-generation cephalosporins, ciprofloxacin, imipenem-cilastatin, meropenem, or piperacillin/tazobactam). In Group B, 22.2% of clinics (median 6; range 2-15) administer antibiotics for three to five days, and 14.8% (median 4; range 1-11) use antibiotics outside SIS guidelines. In Group C, 40.7% of clinics (median 11; range 1-14) administer antibiotics for more than five days, and 14.8% (median 4; range 1-14) use antibiotics that are outside the SIS guidelines. In Group D, 11.1% of clinics (median 3; range 2-5) do not cover Enterococcus with the antibiotics administered. There seems to be confusion in determining the situations with simple contamination of the peritoneal cavity, whose treatment requires short-duration antibiotic administration, and in the type of antibiotics administered to various patient groups, elements that lead to prolonged or erroneous administration of antibiotic drugs. Continuous discussion and surgeon training is imperative and may be the best choice to ensure familiarity with antibiotics and their proper use and thus to minimize serious adverse events and treatment failure.


Physical activity, sleep pattern and energy expenditure in double-handed offshore sailing.
The aim of the present study was to quantify total energy expenditure, activity energy expenditure and time spent at three levels of physical activity (low, moderate, high intensity) in four two-person crews during a 500-mile double-handed sailing regatta. Physical activity intensity and energy expenditure were assessed during a 500-nautical-mile double-handed offshore competition in eight male sailors (46.3±3.4 years; 180±13 cm; 85.4±12.5 kg). During the whole regatta, they wore an activity monitor that estimated energy expenditure and minutes spent at each level of intensity (sedentary, <1.5 METs; light physical activity, 1.5-2.9 METs; moderate physical activity, 3.0-6.0 METs; vigorous physical activity, >6.0 METs). The sailors spent longer periods (P<0.0001) of time in sedentary (823±193 min/day) and light physical activities (516±177 min/day) than in moderate (95±34 min/day) or vigorous (6±4 min/day) physical activities. They slept 5 times per day (±1.4) for 36 min (±9) in each sleeping period. The total energy expenditure was 14.26±1.89 MJ/day and the activity energy expenditure was 5.06±1.42 MJ/day. Activity energy expenditure was significantly correlated with total sleep time, boat speed, and distance covered each day (P<0.05). CONCLUSION;:The high total energy expenditure was more likely a consequence of the short and rare periods of sleep during the competition rather than of the bouts of moderate and vigorous physical activities.


Protease nexin-2/amyloid beta-protein precursor limits cerebral thrombosis.
The amyloid beta-protein precursor (AbetaPP) is best known as the parent molecule to the amyloid beta-peptide that accumulates in the brains of patients with Alzheimer's disease. Secreted isoforms of AbetaPP that contain the Kunitz proteinase inhibitor domain are analogous to the previously identified cell-secreted proteinase inhibitor known as protease nexin-2 (PN2). Although PN2/AbetaPP is enriched in brain and in circulating blood platelets, little is understood of its physiological function and potential role in disease processes outside of amyloid beta-peptide generation. We hypothesized that the potent inhibition of certain procoagulant proteinases by PN2/AbetaPP, coupled with its abundance in platelets and brain, indicate that it may function to regulate cerebral thrombosis. Here we show that specific and modest 2-fold overexpression of PN2/AbetaPP in circulating platelets of transgenic mice caused a marked inhibition of thrombosis in vivo. In contrast, deletion of PN2/AbetaPP in AbetaPP gene knockout mice resulted in a significant increase in thrombosis. Similarly, platelet PN2/AbetaPP transgenic mice developed larger hematomas in experimental intracerebral hemorrhage, whereas AbetaPP gene knockout mice exhibited reduced hemorrhage size. These findings indicate that PN2/AbetaPP plays a significant role in regulating cerebral thrombosis and that modest increases in this protein can profoundly enhance cerebral hemorrhage.


Organocatalytic Atroposelective Synthesis of Isoquinolines via Dynamic Kinetic Resolution.
Herein, a highly enantioselective Pictet-Spengler reaction for the synthesis of axially chiral tetrahydroisoquinolines via dynamic kinetic resolution is described. Chiral phosphoric acids catalyze cyclization to yield single regioisomeric isoquinolines with excellent enantioselectivities around the C-C bond up to 99% ee. The current protocol is effective for a wide range of substrates, and the observed enantiodivergence depends on the substituents on the catalysts.


Hydrogen sulfide improves vascular repair by promoting endothelial nitric oxide synthase-dependent mobilization of endothelial progenitor cells.
Endothelial progenitor cells (EPCs) play a crucial role in endothelial repair after arterial injury. Hydrogen sulfide (H2S) is a novel gasotransmitter that regulates vascular homeostasis. We investigated whether exogenous H2S could facilitate EPCs in repairing arterial injury. Sodium hydrosulfide (NaHS), a precursor of H2S, promoted re-endothelialization and inhibited neointima formation in a rodent carotid artery injury model. Flow cytometric analysis revealed that NaHS treatment significantly increased the yield of EPCs after vascular injury. Furthermore, NaHS enhanced the capacity of EPCs to the luminal surface of injured arteries in wild-type mice, which had received a bone marrow transplantation from tie2-GFP donor mice. However, this enhancing effect was greatly attenuated in endothelial nitric oxide synthase knockout mice (eNOS). In-vitro incubation of human EPCs with NaHS not only increased the yield of EPCs, but also enhanced their adhesion and colony formation capacities. Treatment with an eNOS inhibitor (L-NAME) blocked the effects of NaHS on EPCs functions. H2S enhances eNOS-dependent mobilization of bone marrow-derived EPCs and facilitates re-endothelialization following vascular injury.


Microtubule destabilising agents: far more than just antimitotic anticancer drugs.
Vinca alkaloids have been approved as anticancer drugs for more than 50 years. They have been classified as cytotoxic chemotherapy drugs that act during cellular mitosis, enabling them to target fast growing cancer cells. With the evolution of cancer drug development there has been a shift towards new "targeted" therapies to avoid the side effects and general toxicities of "cytotoxic chemotherapies" such as the vinca alkaloids. Due to their original classification, many have overlooked the fact that vinca alkaloids, taxanes and related drugs do have a specific molecular target: tubulin. They continue to be some of the most effective anticancer drugs, perhaps because their actions upon the microtubule network extend far beyond the ability to halt cells in mitosis, and include the induction of apoptosis at all phases of the cell cycle. In this review, we highlight the numerous cellular consequences of disrupting microtubule dynamics, expanding the textbook knowledge of microtubule destabilising agents and providing novel opportunities for their use in cancer therapy.


Determination of rutin and quercetin in Chinese herbal medicine by ionic liquid-based pressurized liquid extraction-liquid chromatography-chemiluminescence detection.
A novel ionic liquid-based pressurized liquid extraction (IL-PLE) procedure coupled with high performance liquid chromatography (HPLC) tandem chemiluminescence (CL) detection capable of quantifying trace amounts of rutin and quercetin in four Chinese medicine plants including Flos sophorae Immaturus, Crateagus pinnatifida Bunge, Hypericum japonicum Thunb and Folium Mori was described in this paper. To avoid environmental pollution and toxicity to the operators, ionic liquids (ILs), 1-alkyl-3-methylimidazolium chloride ([C(n)mim][Cl]) aqueous solutions were used in the PLE procedure as extractants replacing traditional organic solvents. In addition, chemiluminescence detection was utilized for its minimal interference from endogenous components of complex matrix. Parameters affecting extraction and analysis were carefully optimized. Compared with the conventional ultrasonic-assisted extraction (UAE) and heat-reflux extraction (HRE), the optimized method achieved the highest extraction efficiency in the shortest extraction time with the least solvent consumption. The applicability of the proposed method to real sample was confirmed. Under the optimized conditions, good reproducibility of extraction performance was obtained and good linearity was observed with correlation coefficients (r) between 0.9997 and 0.9999. The detection limits of rutin and quercetin (LOD, S/N=3) were 1.1×10(-2)mg/L and 3.8×10(-3)mg/L, respectively. The average recoveries of rutin and quercetin for real samples were 93.7-105% with relative standard deviation (RSD) lower than 5.7%. To the best of our knowledge, this paper is the first contribution to utilize a combination of IL-PLE with chemiluminescence detection. And the experimental results indicated that the proposed method shows a promising prospect in extraction and determination of rutin and quercetin in medicinal plants.


Compatibility of olfactory ensheathing cells with functionalized self-assembling peptide scaffold in vitro.
Olfactory ensheathing cell (OEC) transplantation is a promising or potential therapy for spinal cord injury (SCI). However, the effects of injecting OECs directly into SCI site have been limited and unsatisfied due to the complexity of SCI. To improve the outcome, proper biomaterials are thought to be helpful since these materials would allow the cells to grow three-dimensionally and guide cell migration. In this study, we made a new peptide hydrogel scaffold named GRGDSPmx by mixing the pure RADA16 and designer peptide RADA16-GRGDSP solution, and we examined the molecular integration of the mixed nanofiber scaffolds using atomic force microscopy. In addition, we have studied the behavior of OECs in GRGDSPmx condition as well as on RADA16 scaffold by analyzing their phenotypes including cell proliferation, apoptosis, survival, and morphology. The experimental results showed that GRGDSPmx could be self-assembled to form a hydrogel. Inverted optical microscopic and scanning electron microscopic analyses showed that OECs are viable and they proliferate within the nanostructured environment of the scaffold. Thiazolyl blue (MTT) assay demonstrated that OEC proliferation rate was increased on GRGDSPmx scaffold compared with the pure RADA16 scaffold. In addition, OECs on GRGDSPmx scaffolds also showed less apoptosis and maintained the original spindle-shaped morphology. Calcein-AM/PI fluorescence staining revealed that OECs cultured on GRGDSPmx grew well and the viable cell count was 95%. These results suggested that this new hydrogel scaffold provided an ideal substrate for OEC three-dimensional culture and suggested its further application for SCI repair.


Epithelial cell proliferation in duodenal ulcer.
Epithelial cell proliferation in the duodenum was investigated in 50 patients by incubating mucosal biopsy samples with tritiated thymidine, followed by autoradiography. Fifteen patients had a normal duodenum, 15 duodenal ulcer undergoing elective surgery, 10 perforated duodenal ulcer, and 5 severe non-ulcer-associated duodenitis. The mean crypt cell labelling index in the duodenal bulb of controls was 8.8 +/- 0.4% (mean +/- SEM), at the edge of perforated ulcers 19.1 +/- 2.0%, at the edge of elective ulcers 18.6 +/- 1.4%, and in biopsy specimens from non-ulcer-associated duodenitis 14.0 +/- 1.2%. The mean labelling index in the distal first part of duodenum of control patients was 9.1 +/- 0.8 similar to the values found in histologically normal specimens distal to ulcer or duodenitis. The results indicate active epithelial cell proliferation in both duodenal ulcer and duodenitis. There was no evidence of impairment of epithelial cell proliferation in duodenal ulcer patients.


How reliable are pseudocontact shifts induced in proteins and ligands by mobile paramagnetic metal tags? A modelling study.
The anisotropic component of the magnetic susceptibility tensor (Δχ tensor) associated with various paramagnetic metal ions can induce pseudocontact shifts (PCSs) and residual dipolar couplings (RDCs) in proteins, yielding valuable restraints in structural studies. In particular, PCSs have successfully been used to study ligands that bind to proteins tagged with a paramagnetic metal ion, which is of great interest in fragment-based drug design. To create easy-to-interpret PCSs, the metal ion must be attached to the protein in a rigid manner. Most of the existing methods for site-specific attachment of a metal tag, however, result in tethers with residual flexibility. Here we present model calculations to quantify the extent, to which mobility of the metal-binding tag can compromise the quality of the Δχ tensor that can be determined from the PCSs observed in the protein. Assuming that the protein can be approximated by a sphere and the tag is attached by a single tether, the results show that a single effective ∆χ tensor can describe the PCSs and RDCs of the protein spins very well even in the presence of substantial tag mobility, implying that PCSs of ligands in binding pockets of the protein can be predicted with similar accuracy. In contrast, the quality of the PCS prediction for nuclear spins positioned above the surface of the protein is significantly poorer, with implications for studies of protein-protein complexes. The simulations probed the sensitivity of the effective Δχ tensor to different parameters, including length of the tether between protein and metal ion, protein size, type and amplitude of tag motion, tensor orientation relative to the protein and direction of tag motion. Tether length and amplitude of motion were identified as two key parameters. It is shown that the amplitude of tag motions cannot be quantified by simple comparisons of the effective Δχ tensor with the alignment tensor determined from RDCs.


Insulin mimetic peptide S371 folds into a helical structure.
Insulin plays a crucial physiological role in glucose control by initiating a number of signaling events on binding and activating its cell surface receptor. Insulin mimics have, therefore, become promising agents for treating diabetes and to probe the mechanism of interaction of insulin with its receptor. Specifically, many insulin-mimetic peptide sequences have been discovered and found to selectively function as agonists and antagonists, but their structures and the mechanistic details of their interactions with the receptor remain challenging to characterize. In this work, we have studied the folding properties and structure of a Site 1 insulin mimetic peptide S371 that has sequence similarities with the insulin B-chain as well as with a critical hormone-binding element of the receptor known as the C-terminal (CT) peptide. We first validated our simulation approaches by predicting the known solution structure of the insulin B-chain helix and then applied them to study the folding of the mimetic peptide S371. Our data predict a helical fold for the first 16 residues of S371 that has a resemblance to the helical motifs in the insulin B-chain and CT. We also propose receptor-bound models of S371 that provide mechanistic explanations for competing binding properties of S371 and CT to the Site 1 of IR. © 2017 Wiley Periodicals, Inc.


[Pharmacological justification for the use of new antidepressant drugs].
This review compares a new generation of antidepressants with standard tricyclic antidepressants. It is now believed that an ideal antidepressant should be characterised by high therapeutic efficacy, good tolerance, safety of use related to low incidence of adverse effects, little potential for interactions and low cost of use. Mirtazapine, nefazodone and venlafaxine have therapeutic efficacy which is comparable with that of tricyclic antidepressants and their lack of (or insignificant) receptor effect as well as double mechanism of action makes them a safer therapeutic option.


Isoenzymes of Superoxide Dismutase in Nodules of Phaseolus vulgaris L., Pisum sativum L., and Vigna unguiculata (L.) Walp.
The activity and isozymic composition of superoxide dismutase (SOD; EC 18.104.22.168) were determined in nodules of Phaseolus vulgaris L., Pisum sativum L., and Vigna unguiculata (L.) Walp. formed by Rhizobium phaseoll 3622, R. Ieguminosarum 3855, and Bradyrhizobium sp. BR7301, respectively. A Mn-SOD was present in Rhizobium and two in Bradyrhizobium and bacteroids. Nodule mitochondria from all three legume species had a single Mn-SOD with similar relative mobility, whereas the cytosol contained several CuZn-SODs: two in Phaseolus and Pisum, and four in Vigna. In the cytoplasm of V. unguiculata nodules, a Fe-containing SOD was also present, with an electrophoretic mobility between those of CuZn- and Mn-SODs, and an estimated molecular weight of 57,000. Total SOD activity of the soluble fraction of host cells, expressed on a nodule fresh weight basis, exceeded markedly that of bacteroids. Likewise, specific SOD activities of free-living bacteria were superior or equal to those of their symbiotic forms. Soluble extracts of bacteria and bacteroids did not show peroxidase activity (EC 188.8.131.52), but the nodule cell cytoplasm contained diverse peroxidase isozymes which were readily distinguishable from leghemoglobin components by electrophoresis. Data indicated that peroxidases and leghemoglobins did not significantly interfere with SOD localization on gels. Treatment with chloroform-ethanol scarcely affected the isozymic pattern of SODs and peroxidases, and had limited success in the removal of leghemoglobin.


Purification of arginine-sensitive hemagglutinin from Fusobacterium nucleatum and its role in coaggregation.
Hemagglutinin of Fusobacterium nucleatum was extracted from Triton X-100-pronase P-treated cell envelopes, and was purified by affinity chromatography on L-arginine agarose. The hemagglutinin was inactivated by heating at 70 degrees C for 1 min. The activity was inhibited by L-arginine but was not affected by any sugars or by EDTA. The hemagglutinin aggregated 14 out of 17 strains of oral streptococci tested, and the bacterial aggregating activity was also inhibited by L-arginine. The results indicate the dominant role of this hemagglutinin in the adherence of this bacterium both to host cells and to other bacteria.


Improving Glycemic Control and Insulin Ordering Efficiency for Hospitalized Patients With Diabetes Through Carbohydrate Counting.
Glycemic control in hospitalized patients is challenging but important for optimal outcomes. Insulin dosing through carbohydrate counting may address patient, provider, and institutional factors that complicate hospital glycemic management. On two surgical units at a tertiary care teaching hospital, we pilot tested postmeal insulin dosing based on carbohydrate counting (plus basal insulin) rather than the current process of ordering scheduled premeal insulin without knowledge of the patient's consumption. Analysis assessed hyperglycemia, hypoglycemia, insulin orders, and nurse and provider satisfaction and confidence. On general surgery, mean glucose level improved from 188 to 137 mg/dl (p < .001). On cardiovascular surgery, mean glucose improved only mildly from 177 to 175 mg/dl (p < .28). No hypoglycemia was reported. Efficiency of mealtime insulin dosing improved through reduced average number of insulin orders per meal from 1.1 to 0.09. Process satisfaction improved for providers (preintervention, 60%; postintervention, 100%), general surgery nurses (preintervention, 72%; postintervention, 100%), and cardiovascular surgery nurses (preintervention, 69%; postintervention, 84%). Confidence in insulin dose accuracy improved for providers (preintervention, 50%; postintervention, 100%), general surgery nurses (preintervention, 59%; postintervention, 100%), and cardiovascular surgery nurses (preintervention, 48%; postintervention, 84%). Carbohydrate counting is effective and efficient and improved staff satisfaction and confidence in hospital mealtime insulin dosing.


Power, desire, and pleasure in sexual fantasies.
One hundred and sixty-two participants (ages 21-45) wrote open-ended sexual fantasies and completed self-report measures of rape myth acceptance, adversarial sexual beliefs, and attitudes toward women. We coded fantasies using a newly developed scoring system that includes themes of dominance, submission, sexual pleasure, and sexual desire. Men fantasized about dominance more than women did; they also tended to focus more on the desire and pleasure of their partner. Desire and pleasure were more closely linked in the fantasies of men than in the fantasies of women, for whom the two were distinct constructs. Although fantasies of submission were not associated with problematic attitudes for either gender, men's fantasies of dominance were associated with greater acceptance of rape myths. For women, greater rape myth acceptance was associated with emotional and romantic fantasy themes.


Segmental Orthodontics for the Correction of Cross Bites.
Cross bite is a condition where one or more teeth may be abnormally malposed buccally or lingually or labially with reference to the opposing tooth or teeth. Cross bite correction is highly recommended as this kind of malocclusion do not diminish with age. Uncorrected cross bite may lead to abnormal wear of lower anteriors and cuspal interference, mandibular shift resulting in mandibular asymmetry and temporomandibular joint dysfunction syndrome. There are several methods for treating this type of malocclusion. In this article, segmental orthodontics has been highlighted by using 2 × 4 appliance therapy and lingual button with cross elastics. This appliance offers many advantages as it provides complete control of anterior tooth position, is extremely well tolerated, requires no adjustment by the patient and allows accurate and rapid positioning of teeth.


Developmental role of DSCAM in spinal locomotor circuits.
Studying the development of spinal circuitry is essential in understanding the motor behaviors that arise from them. In their study, Thiry et al. (J Neurophysiol 115: 1338-1354, 2016) show that loss of Down syndrome cell adhesion molecule (DSCAM) leads to locomotor impairments that may stem from specific changes in spinal connectivity altering the balance of central and peripheral excitatory drive onto spinal motoneurons. These findings as well as additional insights and future directions are discussed in the context of the recent literature.


Can clinical risk factors for late stillbirth in West Africa be detected during antenatal care or only during labour?
Recent studies have shown that the most important risk factors for perinatal mortality in developing countries are not detectable during antenatal care but can be observed only shortly before or during labour. Although 60% of perinatal deaths in these countries are stillbirths, few epidemiological studies focus on them. We tested the hypothesis that the risk factors for late stillbirth in West Africa are detectable principally shortly before or during labour. Data came from a prospective population-based study (the MOMA survey) that collected information about 20 326 pregnant women in seven areas, primarily urban, in West Africa. There were 19 870 singleton births. The stillbirth rate was 25.9 per 1000 total births (95% CI: 23.7-28.1). In the crude analysis, after adjustment and consideration of prevalence, the principal risk factors for late stillbirth were: late antenatal or intrapartum vaginal bleeding, intrapartum hypertension, dystocia, and infection. Other risk factors were: maternal height (<150 cm), maternal age (>35 years), previous stillbirths, hypertension at the 8-month antenatal visit and number of antenatal visits (<2). The principal risk factors for late stillbirth observed in our study could be detected only in the late antenatal and intrapartum period. These results highlight the potential benefits of partograph use. They need to be confirmed by studies incorporating continuous intrapartum fetal monitoring.


Construction of building-blocks for polyether synthesis using sequential catalytic ring-closing enyne and cross metathesis.
Highly functionalised six- and seven-membered cyclic ethers bearing a variety of side chains have been synthesised using ring-closing enyne metathesis and subsequent cross metathesis of the intermediate diene; one-pot enyne and cross metathesis has also been accomplished, allowing ring construction and side chain introduction to be performed in a single operation.


Endometrial cancer patients: a cohort previous to changes in tumour behaviour and treatment strategies.
Nowadays, the incidence of endometrial cancer is rising, especially of high-grade endometrial tumours. Recently, the FIGO classification of endometrial cancer has changed worldwide. Besides that, treatment strategies are changing. The purpose of this study was to analyse the adherence to the national guidelines of cancer treatment and to analyse patterns of disease relapse and survival. We focused on a group of patients (n = 191) with endometrial cancer, in a time period in which new treatment strategies are not yet completely implemented. Because of multiple upcoming changes in patient characteristics, tumour classification, as well as treatment regimens, a more heterogeneous cohort of patients diagnosed with endometrial cancer will appear. From now on, all those changes will have their effects on the followup of conventional endometrial cancer treatment. In our opinion, it is, therefore, valuable to have the current, more homogenous, cohort clearly described.


The cAMP/PKA Pathway Inhibits Beta-amyloid Peptide Release from Human Platelets.
The main component of Alzheimer's disease (AD) is the amyloid-beta peptide (Aβ), the brain of these patients is characterized by deposits in the parenchyma and cerebral blood vessels known as cerebral amyloid angiopathy (CAA). On the other hand, the platelets are the major source of the Aβ peptide in circulation and once secreted can activate the platelets and endothelial cells producing the secretion of several inflammatory mediators that finally end up unchaining the CAA and later AD. In the present study we demonstrate that cAMP/PKA pathway plays key roles in the regulation of calpain activation and secretion of Aβ in human platelets. We confirmed that inhibition of platelet functionality occurred when platelets were incubated with forskolin (molecule that rapidly increased cAMP levels). In this sense we found that platelets pre-incubated with forskolin (20 μM) present a complete inhibition of calpain activity and this effect is reversed using an inhibitor of protein kinase A. Consequentially, when platelets were inhibited by forskolin a reduction in the processing of the APP with the consequent decrease in the Aβ peptide secretion was observed. Therefore our study provides novel insight in relation to the mechanism of processing and release of the Aβ peptide from human platelets.


Lack of correlation between sternocleidomastoid and scalene muscle fatigability and duration of symptoms in chronic neck pain patients.
Despite the evidence of greater fatigability of the superficial cervical flexor muscles in neck pain patients, the relationship between duration of neck pain and muscle fatigue has not been investigated. This study examined the relationship between myoelectric manifestations of sternocleidomastoid (SCM) and anterior scalene (AS) muscle fatigue and duration of neck pain in a group of patients with chronic neck pain. Twenty chronic neck pain patients with a history of pain ranging between 1 and 25 years (mean 6.15, S.D. 5.48 years) participated in this study. Myoelectric signals were recorded from the SCM and AS muscles from the side of greatest pain as patients performed sustained sub-maximal isometric cervical flexion contractions at 25% and 50% of the maximum voluntary contraction (MVC). The initial value and slope of the mean frequency (MNF), average rectified value (ARV) and conduction velocity (CV) of the EMG signals were calculated. Correlation analysis was applied to determine whether a relationship existed between the duration of neck pain and estimates of EMG variables. No significant correlation was found between duration of pain and estimates of the MNF, ARV and CV for either SCM or AS contracting at 25% and 50% MVC. The length of history of neck pain does not appear to correlate with the extent of SCM and AS muscle fatigability in patients with chronic neck pain. This finding may be due to an increase of muscle fatigability occurring within the first few years of neck pain, which is not followed by signs of increased fatigue after this time. This was supported by the finding of significant correlations between duration of pain and AS fatigability on a subgroup of patients with pain duration less than 5 years. Future studies are warranted to examine how early signs of cervical muscle fatigability are evident after the onset of neck pain as this will have implications for rehabilitation.


The multifactorial nature of HIV-1 latency.
HIV-1 can avoid host immune responses and antiretroviral drugs through the latent infection of resting memory CD4(+) T cells. Recently, latent viral genomes have been shown to reside within the introns of active host genes. Therefore, latency is not simply due to an inaccessibility of the integrated proviruses to the transcriptional machinery. Rather, latency might result from insufficient nuclear levels of the crucial activation-dependent host transcription factors required to overcome the transcriptional interference that is an automatic consequence of the nature of HIV-1 integration sites. In addition, resting cells lack sufficient levels of HIV-1 Tat and Tat-associated activation-dependent host factors that are necessary for processive transcription. Defects at consecutive steps of transcriptional initiation and elongation enable HIV-1 to remain hidden within resting CD4(+) T cells.


Nurses's knowledge of heart failure education principles.
The goal of this study was to determine nurses' knowledge of heart failure (HF) self-management education principles. The study was exploratory and descriptive and included a convenience sample. Research took place in a large midwestern health care system that included a university-based hospital, community hospitals, and home or palliative care. Subjects included 300 nurses who provide care to patients with HF. The outcome measures included overall and topic specific perceptions of basic information important to HF self-management. Topics included diet, fluids or weight, signs or symptoms of worsening condition, medications, and exercise. A 20-item, true or false written survey was administered between February 2000 and April 2000. Of the 300 nurses surveyed, 92% were registered nurses and 8% were licensed practical nurses; 38% worked in a large university-based hospital; 44% were employed at 5 community hospitals; and 18% worked in home or hospice-palliative care. Mean HF self-management knowledge score was 15.2 +/- 2.0. Registered nurses scored significantly higher than licensed practical nurses (15.3 vs 14.1; P =.004). Individual questions with overall scores <30% were related to dry or ideal weight in daily weight monitoring (24%), nonsymptomatic, low blood pressure (26%), and short-term dizziness when rising (19%). Individual question scores >30% and < or =75% were related to nonsteroidal anti-inflammatory inhibitor use (49%), potassium-based salt substitute use (52%), rest vs activity (72%), and lean delicatessen meat use in a low sodium diet (75%). In questions with scores <30%, nurses requested more information only 5% to 8% of the time. Overall analysis of variance indicated differences by work experience. HF nurses (primary population) scored higher than critical-care, medical-surgical, or telemetry floor nurses (16.2 +/- 1.7; 15.1 +/- 1.8; and 14.7 +/- 2.0, respectively; P <.001); home care nurses scored higher than hospital or palliative care nurses (15.9 +/- 1.5; 15.1 +/- 2.0; and 14.0 +/- 1.5, respectively; P =.006). Nurses may not be properly educated in HF self-management principles and must be provided with the right information so they can improve the quality and amount of information they offer to patients. Nurses who are better prepared to educate patients with HF may be more likely to carry out this nursing function as a part of their daily job role.


Randomized trial comparing dose reduction and growth factor supplementation for management of hematological side effects in HIV/hepatitis C virus patients receiving pegylated-interferon and ribavirin.
Pegylated-interferon (PEG-IFN) and ribavirin (RBV), current standard treatment for hepatitis C virus (HCV) infection, are frequently associated with neutropenia and anemia, leading to high treatment discontinuation rates in HIV/HCV-coinfected patients. Our objective was to compare the effectiveness of intervening with hematologic growth factors versus dose reductions of standard HCV therapy for the management of treatment-induced hematologic disorders. Ninety-two HIV/HCV-coinfected, therapy-naive subjects received PEG-IFN alfa-2b 1.5 μg·kg⁻¹·wk⁻¹ and RBV 13 ± 2 mg·kg⁻¹·d⁻¹ for up to 48 weeks. Before treatment initiation, subjects were randomized to subsequently receive growth factors, recombinant human erythropoietin (rHuEPO) and/or granulocyte colony-stimulating factor, or dose reduction (RBV and/or PEG-IFN) for anemia and neutropenia management, respectively. We analyzed the ability of each management strategy to control anemia and neutropenia and the percentage of subjects who achieved a successful treatment outcome according to the different management strategies. During treatment, 43 subjects developed anemia (human erythropoietin, n = 24; dose reduction, n = 19), whereas 25 subjects developed neutropenia (granulocyte colony-stimulating factor, n = 10; dose reduction, n = 15). After the intervention, the increase in both hemoglobin and absolute neutrophil counts did not differ between the 2 side effect management strategies. Sustained response percentages were similar comparing anemic and neutropenic subjects regardless of management strategy (anemia: recombinant human erythropoietin, 29% versus dose reduction, 21%, P = 0.92; neutropenia: granulocyte colony-stimulating factor, 40% versus dose reduction, 20%, P = 0.46). Growth factor supplementation and dose reduction do not seem to differ as management strategies for anemia and neutropenia in HIV/HCV-coinfected individuals treated with PEG-IFN/RBV.


[History of blood platelets: from "molecules" to "cell"].
Historical annotations attached to the discovery of platelets as blood cells throughout the 19th century are reported. The so-called "minute molecules" were first connected with the formation of red and white blood cells, or of fibrin as well. The active role of platelets in coagulation was recognized only 30 years later. During that time, it became clear that these "molecules" were "cells", anatomical and physiological entities.


Designer insulins regimens in clinical practice--pilot multicenter Indian study.
Newer insulin analogues viz., premix insulin analogue (biphasic insulin aspart) and insulin glargine are now available in India. A multicenter all-India study was done to document the patient profile and responses to these analogues in routine clinical practice. The study was conducted prospectively at 4 diabetes care clinics in different regions of India and collected data on the use of either of the two regimens A. Premix insulin analogue given twice-daily B. Basal-bolus analogue regimen (insulin aspart with every meal and insulin glargine once-a-day at bedtime). The centers collected all data at 3 time-points--baseline, 4 weeks later and end of 12 weeks. The study measures were FPG (fasting plasma glucose), PPPG (postprandial plasma glucose), HbA1c and insulin dose. FPG and PPPG were recorded at each of the three time points. HbA1c was recorded at baseline and end of study. Safety was assessed based on reported adverse drug reactions and occurrence of hypoglycaemias. Data of 145 patients was available for analysis (n=114 on premix insulin analogue and n=31 on basal-bolus analogue regimen). Baseline demography was comparable in the two groups. Both the regimens lowered all blood glucose parameters including HbA1c significantly as compared to baseline. However, the premix insulin analogue fared better than the basal-bolus regimen in lowering HbA1c (1.58 vs. 1.16% respectively; p<0.05). Also 41% more patients in the premix group could achieve target HbA1c of < 7% at the end of study. The mean insulin dose was lower with the premix analogue group at the end of 12 weeks. There was no significant difference between the two groups in terms of change in body weight. No major hypoglycaemias were reported and the percentage of patients experiencing a minor episode was lower with the premix analogue than the basal-bolus regimen both at 4 and 12 weeks (11.4 vs. 35.48%; 16.7 vs. 58.06% respectively). No adverse drug reactions were reported throughout the study. We conclude that both premix analogue administered twice a day and four times a day basal bolus regimen appear to be a convenient, safe and effective way of initiating insulin therapy in people with type-2 diabetes. The premix analogues achieves target better than the basal bolus regimen as has better compliance.


Learning Multi-View Interactional Skeleton Graph for Action Recognition.
Capturing the interactions of human articulations lies in the center of skeleton-based action recognition. Recent graph-based methods are inherently limited in the weak spatial context modeling capability due to fixed interaction pattern and inflexible shared weights of GCN. To address above problems, we propose the multi-view interactional graph network (MV-IGNet) which can construct, learn and infer multi-level spatial skeleton context, including view-level (global), group-level, joint-level (local) context, in a unified way. MV-IGNet leverages different skeleton topologies as multi-views to cooperatively generate complementary action features. For each view, separable parametric graph convolution (SPG-Conv) enables multiple parameterized graphs to enrich local interaction patterns, which provides strong graph-adaption ability to handle irregular skeleton topologies. We also partition the skeleton into several groups and then the higher-level group contexts including inter-group and intra-group, are hierarchically captured by above SPG-Conv layers. A simple yet effective global context adaption (GCA) module facilitates representative feature extraction by learning the input-dependent skeleton topologies. Compared to the mainstream works, MV-IGNet can be readily implemented while with smaller model size and faster inference. Experimental results show the proposed MV-IGNet achieves impressive performance on large-scale benchmarks: NTU-RGB+D and NTU-RGB+D 120.


Validation of the Palliative Prognostic Index, Performance Status-Based Palliative Prognostic Index and Chinese Prognostic Scale in a home palliative care setting for patients with advanced cancer in China.
The predictive value of the prognostic tool for patients with advanced cancer is uncertain in mainland China, especially in the home-based palliative care (HPC) setting. This study aimed to compare the accuracy of the Palliative Prognostic Index (PPI), the Performance Status-Based Palliative Prognostic Index (PS-PPI), and the Chinese Prognosis Scale (ChPS) for patients with advanced cancer in the HPC setting in mainland China. Patients with advanced cancer admitted to the hospice center of Yuebei People's Hospital between January 2014 and December 2018 were retrospectively calculated the scores according to the three prognostic tools. The Kaplan-Meier method was used to compare survival times among different risk groups. Receiver operating characteristic curve analysis was used to assess the predictive value. The accuracy of 21-, 42- and 90-day survival was compared among the three prognostic tools. A total of 1863 patients were included. Survival time among the risk groups of all prognostic tools was significantly different from each other except for the PPI. The AUROC of the ChPS was significantly higher than that of the PPI and PS-PPI for 7-, 14, 21-, 42-, 90-, 120-, 150- and 180-day survival (P < 0.05). The AUROC of the PPI and PS-PPI were not significantly different from each other (P > 0.05). The ChPS is more suitable than the PPI and PS-PPI for advanced cancer patients in the HPC setting. More researches are needed to verify the predictive value of the ChPS, PPI, and PS-PPI in the HPC setting in the future.


[Effect of Acupuncture on Expression of Receptor Tyrosine Kinase c-kit in Interstitial Cells of Cajal, Carbon Monoxide and Heme Oxygenase in Colon Tissue After Colonic Anastomosis in Rats].
To observe the effect of acupuncture on expression of receptor tyrosine kinase (RTK) c-kit in interstitial cells of Cajal (ICCs), carbon monoxide (CO) and heme oxygenase (HO) in colon tissue after colonic anastomosis, so as to explore the mechanism of acupuncture in improving gastrointestinal motility. SD rats were randomly devided into control group, model group and acupuncture group. The model was established using colonic anastomosis. Each group was further devided into 3, 5, and 10 d (time-point) subgroups (n=10 in each). Acupuncture was applied to acupuncture group at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6) and "Taichong" (LR 3) for 15 min, once daily after modeling. The first defecation time was recorded, and the intestinal propulsive rate was measured. The expression of c-kit in colon tissue was detected by immunohistochemistry. The content of CO, the activities of HO-1 and HO-2 in colon tissue were detected by biochemical method and ELISA, respectively. Compared to the control group, the intestinal propulsive rate and the expression level of c-kit in ICCs were decreased in the model group(P<0.05), the content of CO and the activity of HO-1 were increased in model 3 d and 5 d subgroups(P<0.05), the activity of HO-2 was increased in model 3 d subgroup(P<0.05), while the opposite results appeared in model 5 d and 10 d subgroups(P<0.05). Compared to the model group, the first defecation time was shortened (P<0.05), the intestinal propulsive rate and the expression level of c-kit in ICCs were increased in the acupuncture group (P<0.05), the content of CO and the activity of HO-1 were decreased in acupuncture 3 d and 5 d subgroups(P<0.05), the activity of HO-2 was decreased in acupuncture 3 d subgroup(P<0.05), while the opposite result appeared in acupuncture 10 d subgroup(P<0.05). Compared to the 3 d subgroup, the intestinal propulsive rate and the expression level of c-kit in ICCs were increased, the content of CO, the activities of HO-1 and HO-2 were decreased in both model and acupuncture 5 d subgroups (P<0.05). In model 10 d subgroup, the intestinal propulsive rate and the expression level of c-kit in ICCs were increased, the content of CO and the activity of HO-1 were decreased in comparison with the model 5 d subgroup(P<0.05). Acupuncture can improve postoperative gastrointestinal motility by declining CO content and HO-1 and HO-2 activity in colon tissue, and promoting ICCs restoration.


Biotransformation of the fungal toxin fomannoxin by conifer cell cultures.
Fomannoxin [(+/-)-5-Formyl-2-isopropenyl-2,3-dihydrobenzofurane] is a phytotoxic secondary metabolite, which is produced by the forest pathogenic basidiomycete Heterobasidion annosum during the infection process. Fomannoxin shows growth-inhibiting effects on callus and suspension cultures of conifer cells. By investigating the interaction of the phytotoxin with Pinus sylvestris cells a detoxification of fomannoxin was detected, presumably as a defense reaction of the plant cells. Undifferentiated green cell lines of Pinus sylvestris were used as target cells. To provide rac-fomannoxin as a substrate a simple method for the chemical synthesis was developed. It was found that the aromatic aldehyde group is reduced by the plant cells producing the non-toxic fomannoxin alcohol which was isolated and identified by spectroscopy. After longer incubation times, also fomannoxin acid-beta-glucoside could be isolated as another detoxification metabolite. For comparison this glucoside was also synthesized.


WhatsApp in mHealth: design and evaluation of an mHealth tool to share dynamic images in hemodynamics.
WhatsApp, like many other messaging Apps, enables messages, documents, and multimedia elements to be exchanged through a chat-based tool. Among the many potentialities of WhatsApp are: (I) the possibility to create groups (WhatsApp Groups) and (II) the possibility to install the app on a personal computer using the WhatsApp Web application. The two functionalities (I, II) were used to set-up an mHealth environment for teleconsultation in telecardiology which will support the exchange of the dynamic images in hemodynamics. A proper client/server architecture was proposed to supply the mHealth environment. The files related to the dynamic study were preliminarily converted [using picture archiving and communication system (PACS) functions] into an audio-video interleave (AVI) format, which is compatible with mobile technology. The mHealth environment was configured. Five dynamic images were extracted from the PACS in the format AVI. The images were exchanged using WhatsApp Web on the server side and WhatsApp on the client side (smartphones). An acceptance analysis of five observers showed high satisfaction with the methodology. From a global perspective, our contribution aligns with those of scholars in the field concerning the use of WhatsApp in medical imaging. Furthermore, this study suggests that research in the telecardiology field can be strengthened through the use of dynamic images and WhatsApp.


Metabolomics profiling of haloperidol and validation of thromboxane-related signaling in the early development of zebrafish.
Haloperidol is a common butyrophenone-derivative antipsychotic drug that is used clinically to treat schizophrenia and to control Tourette disorder. Haloperidol has been shown to be an embryonic toxicant and to cause a variety of adverse effects that affect human embryonic development. However, the pathway impaired by haloperidol during the developmental stages remains unclear. To elucidate the innate toxicological pathway of haloperidol, we investigated the lethality of haloperidol during the embryonic development of zebrafish. We observed that haloperidol caused serious morphological changes, with an LD50 of 9.7 x 10-6 ± 2.4 x 10-6 μg/L. Next, we established a systematic approach to perform metabolite profiling in embryonic zebrafish with various concentrations of haloperidol and analyzed the metabolites using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS). A total of 304 metabolites were identified and 86 metabolites were chosen to predict potential pathways. Among the metabolites, we found through prediction that numerous metabolomics-biological pathways are associated with haloperidol, including peroxisome-proliferator-activated receptor (ppar), thromboxane, and mTOR signaling. Quantitative real time-qPCR was then used to validate the gene expression potentially associated with the thromboxane, which is a metabolic product of arachidonic acid and considered to be important for cell proliferation and the inflammatory response. To sum up, analysis of metabolites in the zebrafish model provides a system for mining biomarkers that reflect biological significance and highlight the therapeutic potency in humans. In addition, it may show potential for application to other pharmaceuticals to identify their various activities and clarify functional mechanisms in the future.


Cold-induced anesthesia impairs path integration memory in dung beetles.
Path integration is a general mechanism used by many animals to maintain an updated record of their position in relation to a set reference point.1-11 To do this, they continually integrate direction and distance information into a memorized home vector. What remains unclear is how this vector is stored, maintained, and utilized for successful navigation. A recent computational model based on the neuronal circuitry of the insect central complex suggests that home vector memories are encoded across a set of putative memory neurons and maintained through ongoing recurrent neural activity.12 To better understand the nature of the home vector memory and experimentally assess underlying mechanisms for maintaining it, we performed a series of experiments on the path integrating dung beetle Scarabaeus galenus.13 We found that, while the directional component of the home vector was maintained for up to 1 h, the distance component of the vector memory decreased gradually over time. Using cold-induced anesthesia, we disrupted the neural activity of beetles that had stored a home vector of known length and direction. This treatment diminished both components of the home vector memory, but by different amounts-the homing beetles lost their distance memory before their directional memory. Together, these findings present new insights into the functional properties of home vector memories and provide the first empirical evidence that a biological process that can be disrupted by cold-induced anesthesia is essential to support homing by path integration.


Tissue factors influencing growth and maintenance of endometriosis.
The unpredictable response of endometriosis to steroids and its recurrence after therapy, led us to hypothesize a possible further control of this pathology by factors other than steroids. The presence of estrogen, progesterone and epidermal growth factor receptors (ER, PR, EGFr) was evaluated using immunohistochemistry before and after therapy with Danazol or a gonadotropin-releasing hormone analogue (GnRHa), Buserelin. EGFr, ER and PR were present in 100% of endometrial specimens, and in 71%, 29% and 49% of endometriotic implants, respectively. Danazol and GnRHa reduced immunohistochemical staining for EGFr antisera in the endometrial and endometriotic specimens. About 21% of endometriosis were EGFr positive and ER negative, suggesting a potential role of epidermal growth factor in growth and maintenance of endometrial ectopia.


Wintertime particulate mass concentrations in urban environment and the impact of economic crisis.
The aim of the specific study is to discuss the impact of economic crisis on air quality in Greece in terms of particulate matter (PM) concentrations. For this purpose, three sampling campaigns were conducted during the winter period of 2012, 2013 and 2014 in two medium sized cities in North Greece (Kavala and Drama). The average concentrations measured ranged from 33-56, 28-47 and 25-44 μg/m(3) for PM10, PM2.5 and PM1, respectively. The analysis of the daily concentration profile for all measurements indicated two distinct periods of elevated concentrations: a) during 08:00 to 10:00 and b) during 19:00 to 22:00. The observed periods of increased concentration coincided with the periods of increased urban traffic in the morning and basic heating needs in late evening. Significant correlation was observed between PM10-PM2.5 (R(2)>0.9) and PM2.5-PM1 (R(2)∼1.0) suggesting that coarse and fine particles originate from similar sources. The PM2.5/PM10 ratio values ranged from 0.84 to 0.85 indicating a major impact of PM2.5 to the final concentration levels recorded. The results presented in the specific study support the notion that a significant alteration is undergoing to the atmospheric air quality in Greece due to the economic crisis and the subsequent increase of biomass products combustion for residential heating. Supplemental materials are available for this article.


Heat Inducible Expression of a Chimeric Maize hsp70CAT Gene in Maize Protoplasts.
The response of maize (Zea mays L.) protoplasts to high temperature stress was investigated. After isolation and electroporation, protoplasts were preincubated for 12 hours at 26 degrees C then incubated for 6 hours at elevated temperatures. The pattern of polypeptides synthesized by these protoplasts during the last hour was monitored by in vivo labeling with (35)S-methionine. Incubation at 40 degrees and 42 degrees C resulted in the synthesis of polypeptides not detectable at 26 degrees C. Introduction of a chimeric maize heat shock protein 70 promoter-chloramphenicol acetyltransferase coding region gene into protoplasts via electroporation resulted in the temperature-dependent induction of chloramphenicol acetyltransferase activity with maximal activity at 40 degrees C. In the same protoplasts, a second chimeric gene, in which the firefly luciferase coding region was under the control of the 35S promoter from cauliflower mosaic virus, did not show an increase in expression after incubation at higher temperatures. Maize protoplasts provide a system to study molecular responses to high temperature stress.