Microplastics release phthalate esters and cause aggravated adverse effects in the mouse gut.
Increasing evidence shows that microplastics (MPs) have the potential to act as carriers and transport contaminants into organisms, as well as induce serious health risks. Here we endeavored to address for the first time whether MPs could transport and release phthalate esters (PAEs) into mouse gut and the consequential toxic effects. As a result, MPs could adsorb PAEs, transport PAEs into the gut and cause intestinal accumulation. The accumulation of PAE in the gut followed the order of DEHP > DBP > DEP > DMP, which was the same order for the adsorption of PAEs on MPs. After exposed to DEHP-contaminated MPs for 30 days, significantly increased intestinal permeability and enhanced intestinal inflammation were induced compared with individual MPs and DEHP according to biochemical and histological analysis. Transcriptomic analysis found that 703 genes were differentially regulated and these genes are involved in oxidative stress, immune response, lipid metabolism, and hormone metabolism. Moreover, gut microbiota analysis found that the combined exposure of MPs and DEHP also caused alterations in gut microbiota composition, especially some energy metabolism and immune function related bacteria were significantly changed in the relative abundance. The aggravated effects on intestinal inflammation and metabolic disorders caused by DEHP-contaminated MPs may attribute to increased DEHP accumulation, changed exposure pathway, and shared toxic mechanisms. Our results provide valuable information for the health risk of MPs and plastic additives.


A modified assay for the enumeration of ascaris eggs in fresh raw sewage.
Soil-transmitted helminths (STHs) pose a significant public health problem, infecting approximately 2 billion people globally. Despite relatively low prevalence in developed countries, the removal of STHs from wastewater remains crucial to allow the safe use of biosolids or recycled water for agriculture. Wastewater helminth egg count data can contribute to an assessment of the need for, or success of, a parasite management program. Although the World Health Organisation (WHO) has recommended a standard method for counting helminth eggs in raw sewage based on the method of Bailenger (Ayres et al., 1996), the method generally results in low percentage egg recoveries. Given the importance of determining the presence of STHs, it is essential to develop novel techniques that optimise the recovery rate of eggs from raw sewage. In the present study: •The method described by Bowman et al. (2003) was optimized for the concentration and enumeration of helminth eggs in raw sewage from municipal sewage treatment plants.•The method is simple and reproducible and recovers a greater percentage of helminth eggs compared to the WHO method.


A laser-microfabricated electrohydrodynamic thruster for centimeter-scale aerial robots.
To date, insect scale robots capable of controlled flight have used flapping-wings for generating lift, but this requires a complex and failure-prone mechanism. A simpler alternative is electrohydrodynamic (EHD) thrust, which requires no moving mechanical parts. In EHD, corona discharge generates a flow of ions in an electric field between two electrodes; the high-velocity ions transfer their kinetic energy to neutral air molecules through collisions, accelerating the gas and creating thrust. We introduce a fabrication process for EHD thruster based on 355 nm laser micromachining, which potentially allows for greater materials selection, such as fiber-based composites, than is possible with semiconductor-based lithographic processing. Our four-thruster device measures 1.8 × 2.5 cm and is composed of steel emitters and a lightweight carbon fiber mesh. We measured the electrical current and thrust of each thruster of our four-thruster design, showing agreement with the Townsend relation. The peak thrust of our device, at 5.2 kV, was measured to be 3.03 times its 37 mg (363.0 μN) mass using a precision balance. In free flight, we demonstrated liftoff at 4.6 kV.


TNU-9 Zeolite: Aluminum Distribution and Extra-Framework Sites of Divalent Cations.
The TNU-9 zeolite (TUN framework) is one of the most complex zeolites known. It represents a highly promising matrix for both acid and redox catalytic reactions. We present here a newly developed approach involving the use of 29 Si and 27 Al (3Q) MAS NMR spectroscopy, CoII as probes monitored by UV/Vis and FTIR spectroscopy, and extensive periodic DFT calculations, including molecular dynamics, to investigating the aluminum distribution in the TUN framework and the location of aluminum pairs and divalent cations in extra-framework cationic positions. Our study reveals that 40 and 60 % of aluminum atoms in the TNU-9 zeolite are isolated single aluminum atoms and aluminum pairs, respectively. The aluminum pairs are present in two types of six-membered rings forming the corresponding α and β (15 and 85 %, respectively, of aluminum pairs) sites of bare divalent cations. The α site is located on the TUN straight channel wall and it connects two channel intersections. The suggested near-planar β site is present at the channel intersection.


[The Pediatric Urology Conference].
This meeting was first established in 1972 for the purpose to make free discussion between the urologists and pediatric surgeons on pediatric urology. Several themes, such as undescended testis, hydronephrosis, intersex and stone disease, have been talked over. Ano-rectal malformation was one of the main themes, and many different opinions from both urological and surgical sides have been presented for the prevention of the complications of pelvic surgery. Pediatric urology has undergone a remarkable progress in the past 30 years. The main contribution has been brought about through the better understanding of the diseases in this field. Newer diagnostic methods and operative techniques have also influenced the development. What is left for the future in pediatric urology is how to preserve the renal function. It is not rare that the diseased child goes on to the end-stage renal failure, in spite of the successful intervention of urinary tracts. Hypodysplasia of the kidney is still incurable in the modern medicine. The best alternative may be renal transplantation. Pediatric urology is one member of a team of specialists to whom cases are referred by pediatricians and obstetricians. Earlier diagnosis, for example by the echogram of the fetus, and higher operative techniques are the themes in the future.


[Medical applications of the magnet from antiquity to the nineteenth century].
Although the magnet was a marginal therapeutic mean, it was employed from antiquity to the XIXth century, either to treat various ailments by application on the skin or by absorption, or to take out alien metallic bodies. It was used in its natural magnet or magnetic stone form till the XVIIth century, and under the form termed synthetic magnet or tempered steel made magnet starting with the XVIIth century. These applications are listed in chronological order here, pointing out how remarkably continuous has been the use of the magnet by medicine for many centuries.


Increase in opening angle in hypertension off-loads the intimal stress: a simulation study.
The stress distribution in the vessel wall has important bearing on vascular function including intima, media, and adventitia. The residual strain in the vessel wall has been thought to largely normalize the transmural stress distribution with slightly higher values at the intima. In hypertension, the compensatory increase in opening angle is thought to maintain a uniform stress distribution. We have recently shown that the circumferential stress at adventitia may exceed that at intima at physiological loading due to large opening angle (OA) in normal porcine coronary arteries. The objective of this study was to show that increases in opening angle subsequent hypertension can further shift the stress from the intima to the adventitia. The change in stress distribution during acute hypertension was calculated using available data on the changes in vessel geometry, material property, and internal pressure during hypertension. It was found that the increase in OA following acute hypertension off-loads the stress from intima to adventitia, therefore, relieving some of the stress increase in the intimal layer induced by the sudden pressure increase. This has important implications for hypertension where it may shift the excessive stress from the inner layer to the outer layer. This may be a protective mechanism for the intima layer in hypertension.


ED utilization of computed tomography in a poisoned population.
The objective of this prospective, analytic study was to identify predictors and describe the demographic and clinical correlates of head computed tomography (CT) evaluation in patients with poisoning or drug overdose and altered mental status. Forty-three patients that were evaluated by head CT and 109 that were not evaluated by head CT were entered into the study at a poison control center. None of the 43 scanned patients had any acute findings on head CT. A logistic regression model yielded 4 predictors that were statistically associated with the ordering of a head CT scan: Glasgow Coma Scale (GCS) < or = 8 (odds ratio [OR]: 2.3; 95% confidence interval [CI] 1.03-5.7); age > or = 41 years (OR 5.3; 95% CI 2.2-13); use of drugs or abuse by history (OR 2.8; 95% CI 1.04-7.6); and witnessed seizure activity (OR 4.8; 95% CI 1.3-17.9). We also tested 2 additional models to identify predictors of hospital admission, 1 with and 1 without CT scan included as a covariate. In the first model, only GCS </=8 was a significant predictor of admission (OR 10.7; 95% CI 2.4-47.2). When the use of head CT was added to the second model, it also emerged as an independent explanatory predictor of admission (OR 4.8; CI 95% 1.2-20.4) in addition to GCS (OR 10.1; 95% CI 2.2-45.4). In this pilot study, patients presenting to the emergency department (ED) with suspected poisoning or drug overdose were found to have a low likelihood of abnormal findings on head CT scan. Those among whom CT scans were obtained were more likely to be admitted to the hospital from the ED, despite negative findings.


Nine new species of the "aeruginosus"-group in Amynthas (Clitellata: Megascolecidae) from Nam Et-Phouley National protected Area, Laos.
Nine new species of Amynthas (Clitellata: Megascolecidae) from Mt. Phouleoi, Lao PDR: Earthworm specimens were collected on the top of Mt. Phouleoi, Viengthong District, Houaphanh province, Lao PDR. The new species belonged to pheretimoid earthworms. They have spermathecal pores in 7/8 and 8/9, corresponding to the aeruginosus-group as characterized by Sims and Easton (1972). Their names are: Amynthas bouatongi sp. nov., Amynthas hoauykanangensis sp. nov., Amynthas phimpheti sp. nov., Amynthas nametensis sp. nov., Amynthas somechanae sp. nov., Amynthas wiggeri sp. nov., Amynthas fleischmani sp. nov., Amynthas antethecus sp. nov., and Amynthas elenabondae sp. nov. With the exception of A. nametensis sp. nov., all have the first dorsal pore in an unusually anterior location close to 5/6 and very large, often coiled, prostatic ducts. Several species have slight intraparietal invaginations of the primary male pores, but the similarity of other characters leads us to include them in Amynthas rather than in a polyphyletic Metaphire. Amynthas bouatongi sp. nov. has male pores 0.20-0.24 circumference apart on reniform male pads, pair genital papillae medial and lateral to male pores in XVIII. Amynthas hoauykanangensis sp. nov. has openings of copulatory pouches 0.19-0.25 circumference apart, and paired round genital papillae on postsetal XVII and presetal XIX in line with the male pores. Amynthas phimpheti sp. nov. has male pores 0.21-0.24 circumference apart, round thickened genital papillae paired on 17/18 and 18/19 in line with male pores. Amynthas nametensis sp. nov. has male pores superficial on thickened circular pads, 0.24-0.27 circumference apart. Amynthas somechanae sp. nov. has male pores 0.20-0.33 circumference apart, and paired equatorial papillae in XVIII. Amynthas wiggeri sp. nov. has male pores 0.22-0.30 circumference apart, paired genital papillae equatorial on XVIII medial to male pores and paired papillae equatorial in XVII and XIX. Amynthas fleischmani sp. nov. has openings of copulatory pouches 0.24 circumference apart, paired conical genital papillae equatorial on XVII and XIX; paired circular papillae in intersegmental furrows of 17/18 and 18/19. Amynthas antethecus sp. nov. has openings of copulatory pouches 0.31 circumference apart, paired circular papillae in intersegmental furrow of 17/18 and equatorial on XIX, slightly medial to secondary male pores. Amynthas elenabondae sp. nov. has openings of copulatory pouches 0.19 circumference apart, crescent, convex medially; primary male pore on tubercle on lateral wall of shallow parietal invagination.


Free combined composite flaps using the lateral circumflex femoral system for repair of massive defects of the head and neck regions: an introduction to the chimeric flap principle.
Chimeric composite flaps combined using microanastomoses consist of two or more flaps or tissues, each with an isolated pedicle and a single vascular source. Free combined chimeric flaps using the lateral circumflex femoral system were used to treat massive composite defects of the head and neck in 10 cases. A combined anterolateral thigh flap and vascularized iliac bone graft based on the lateral circumflex femoral system and the deep circumflex iliac system was the most commonly used combination. An anteromedial thigh flap and a paraumbilical perforator-based flap were also combined with this principal combination. The advantages of this chimeric flap over other osteocutaneous flaps are: (1) The flap is relatively thin and the pedicle vessels are up to 10 cm longer and are wider than those of other flaps for easier harvesting of the flap. (2) It is unnecessary to reposition the patient. (3) The vascular pedicle to the skin can be separated from that of the bone. (4) The donor site is not close to the recipient site. (5) The donor scar is in an unexposed area. (6) The skin territory of this flap is extremely wide. (7) A combined anterolateral and anteromedial thigh flap and vascularized iliac bone graft can be easily obtained as an extended combined osteocutaneous flap. (8) Other neighboring skin flaps, such as a groin flap, a paraumbilical perforator-based flap, or a medial thigh flap, can be combined with this chimeric flap because several major muscle branches to be anastomosed derive from the lateral circumflex femoral system. Chimeric composite flaps using the lateral circumflex femoral system are considered suitable for the repair of massive composite defects of the head and neck.


[Arthroscopic subscapularis augmentation for the treatment of recurrent dislocation of shoulder with severe glenoid injury].
To investigate the method and clinical effects of the treatment of recurrent shoulder dislocation with severe glenoid injury by arthroscopic subscapularis augmentation. From March 2019 to August 2020, 16 patients with recurrent dislocation of shoulder with severe glenoid injury underwent arthroscopic subscapularis augmentation, including 10 males and 6 females, aged from 18 to 50 years old with an average of (29.06±10.54) years old, 4 cases of left shoulder and 12 cases of right shoulder.Visual analogue scale (VAS), American Shoulder and Elbow Surgeons (ASES) score and Rowe score were used to evaluate shoulder function and stability before and after operation. All the 16 patients were followed up from 12 to 29 months, with an average of (18.75±7.26) months. VAS score decreased from 5.25±1.13 before operation to 1.37±0.65 at the final follow-up;ASES score increased from 59.44±9.93 before surgery to 90.88±4.00 at the final follow-up; Rowe score of shoulder increased from 51.56±8.89 before surgery to 92.19±7.06 at the final follow-up, and the differences were statistically significant (P<0.05). No dislocation was observed during follow-up. No clinical complications such as incision infection, vascular and nerve injury occurred in all patients after operation. Arthroscopic subscapularis augmentation in the treatment of recurrent dislocation of shoulder with severe glenoid injury is satisfactory. It is an effective treatment method of recurrent dislocation of shoulder joint with severe glenoid injury, and external rotation function in patients with almost unaffected.


Vagus nerve stimulation: a novel approach for prevention and control of refractory seizures.
In order to understand the brain function and to treat various neuropsychiatric illnesses including epilepsy, continued search and discovery of newer antiepileptic drugs has failed to revolutionize the approach in the management of this complex disorder. Moreover, in close to 30% of epilepsy patients, the seizure control is either not satisfactory or it is intractable to pharmacotherapy. Amongst the non-pharmacological treatment options for refractory epilepsy, vagus nerve stimulation occupies a unique position as an adjunctive treatment in prevention and control of partial-onset seizures in adults and adolescents older than 12 years. Though the precise mode of action of VNS is still debatable an honest attempt has been mode here to review all possible literatures available on VNS to establish its role in the management of this complex disorder.


Presence of the d8/17 B-cell marker in children with rheumatic fever in Israel.
A genetic predisoposition to rheumatic fever (RF) has been suspected by several researchers. Ten years ago, using monoclonal antibodies, the B-cell alloantigen D8/17 was identified in 90-100% of patients with RF. The aim of the present study was to evaluate whether the marker is found in patients with RF in Israel, where the population is made up of diverse ethnic groups. The Schneider Children's Medical Center in Petah Tikva, Israel, was the setting for this study. The population included 22 children with RF and nine ethnically matched, disease-free individuals who served as controls. Each of the patients and controls were tested for the B-cell antigen with flow cytometry assay by using monoclonal antibodies. The main outcome measure was the difference in the presence of the D8/17 B-cell marker between the patients with RF and the controls. The mean percentage of B-cells expressing the marker was 11.5 +/- 2.9 in the patients and 4.24 +/- 2.7 in the controls (P < 0.001). There was no statistically significant difference in the frequency of the marker by ethnic origin. The present results support earlier studies suggesting that D8/17 is a disease-specific marker with a world-wide distribution which may potentially serve as an additional diagnostic tool in patients with suspected RF.


Oplopanax horridus: Phytochemistry and Pharmacological Diversity and Structure-Activity Relationship on Anticancer Effects.
Oplopanax horridus, well-known as Devil's club, is probably the most important ethnobotanical to most indigenous people living in the Pacific Northwest of North America. Compared with the long history of traditional use and widespread distribution in North America, the study of O. horridus is relatively limited. In the past decade, some exciting advances have been presented on the phytochemistry and pharmacological diversity and structure-activity relationship on anticancer effects of O. horridus. To date, no systematic review has been drafted on the recent advances of O. horridus. In this review, the different phytochemicals in O. horridus are compiled, including purified compounds and volatile components. Animal and in vitro studies are also described and discussed. Especially, the potential structural-activity relationship of polyynes on anticancer effects is highlighted. This review aimed to provide comprehensive and useful information for researching O. horridus and finding potential agents in drug discovery.


Differential Codon Usage Pattern of HIV-1 tat Gene in Those with Slower and Faster Rates of Disease Progression.
Codon usage has been identified as one of the most important factors that influence gene expression. The frequencies with which the different codons are used vary significantly between different organisms and also between the genes within the same organism. HIV has a remarkable nucleotide composition with an above average percentage of "A" nucleotides resulting in a codon usage pattern different from that of the human host. In this study, we compared the codon usage pattern of HIV-1 genes among different groups of HIV disease progressors to understand the influence of differential codon usage pattern on the pathogenic manifestation in the host.


Self-concept and attraction for similar and dissimilar others.
The present study investigated the role of self-concept as a moderator of the similarity-attraction relationship described by Byrne. Subjects conducted face-to-face interviews with confederates who played roles as job applicants. Similarity-dissimilarity was manipulated by the confederate roles as well as by the information given the subjects in accordance with the procedures described by Byrne. The hypothesis was tested and confirmed that persons with favorable self-concepts would be more attracted to others with similar attitudes than to others with dissimilar attitudes. Persons with negative self-concepts did not show a preference for similar others. It was suggested that earlier studies in this area suffered from methodological flaws and did not constitute an adequate test of the hypothesis. Suggestions for future work in the area were given.


Superconformal Bottom-Up Cobalt Deposition in High Aspect Ratio Through Silicon Vias.
This work demonstrates void-free cobalt filling of 56 μm tall, annular Through Silicon Vias (TSVs) using a mechanism that couples suppression breakdown and surface topography to achieve controlled bottom-up deposition. The chemistry, a Watts electrolyte containing a dilute suppressing additive, and processes are described. This work extends understanding and application of the additive-derived S-shaped Negative Differential Resistance (S-NDR) mechanism, including previous demonstrations of superconformal filling of TSVs with nickel, copper, zinc and gold.


Awareness of Usher Syndrome and the Need for Multidisciplinary Care: A Cross-Occupational Survey of Allied Health Clinicians.
Usher syndrome is the most common cause of deaf-blindness, affecting up to 1 in 6000 people. Multidisciplinary care is required to maximize outcomes for individuals and families. This study assessed awareness of Usher Syndrome amongst allied health clinicians who provide care related to the primarily affected senses of hearing and vision, ie, optometry, orthoptics and audiology. A prospective cross-sectional online survey of clinicians working in Australian university-affiliated clinics (7 optometry, 1 orthoptics and 4 audiology) was completed between September 2021 and January 2022. Questions were asked about the cause, common symptoms, and awareness of health professions who manage Usher syndrome. The 27 audiologists, 40 optometrists, and 7 orthoptists who completed the survey included 53 females (71.6%), had an average age of 37 years (range 24-70), and had an average duration of clinical experience of 13 years (range 1-45 years). The majority of respondents correctly identified Usher syndrome as a genetic condition (86%), identified at least two of the affected senses (97%), and identified the progressive nature of the vision and hearing losses (>90%). Awareness of vestibular dysfunction and its characteristics was low, as was knowledge of the key treatment roles that speech pathologists, genetic counsellors and geneticists play in the management of Usher Syndrome. The majority of respondents also did not identify important aspects of care within their own discipline. This study has shown that there is a need for targeted education to be delivered to hearing and vision care allied health clinicians to raise awareness of the vestibular impacts and aspects of vision loss experienced by people with Usher syndrome. This education needs to target the broad range of clinicians who have a key role in providing multidisciplinary care (including speech pathologists, geneticists, and genetic counsellors) and to identify the key aspects of good-quality multidisciplinary care.


Quantitative sectioning and noise analysis for structured illumination microscopy: erratum.
We correct an error in the original manuscript, where an unrecognized assumption was made about the relationship between the out-of-focus light and the in-focus light. We summarize the condition under which the assumption may still hold, and mention alternative methods researchers can use to obtain accurate quantitative sectioning.


Modulation of executive attention by threat stimulus in test-anxious students.
The study examined whether test anxiety (TA) is related to impaired attentional networks under emotional distraction. High and low test-anxious students completed a modified version of the attention network test (ANT) in which emotional distracters, specifically threat-related or neutral words, were embedded in centrally presented hollow arrows in Experiment 1. Results showed a significant reduction in efficiency of the executive attention in test-anxious students compared to controls when the fillers were threat/test-related words. To evaluate the effect of the test adaptation, the original ANT, which utilized no emotional distracter, was employed as a control task in Experiment 2. We then consolidated the data on efficiency of attentional networks, which were derived from both tasks. Contrasting the two tasks showed that TA reduced executive attention in the revised task only, suggesting an enhanced sensitivity provided by the adaptation from the original task. Taken together, these findings indicate that the attentional deficit in test-anxious individuals represents a situation-related defect of a single component of attention rather than an underlying structural and universal attentional deficit. The results support the hypothesis of attentional control theory and contribute to the understanding of attentional mechanisms in individuals with TA.


Quality and outcomes in anaesthesia: lessons from litigation.
Healthcare litigation in the UK continues to grow at an alarming rate, with claims against anaesthetists and critical care physicians increasing each year. This has led to a huge financial burden for the taxpayer and a sharp increase in professional indemnity fees for individual doctors. Although such litigation should provide valuable information to educate practitioners and reduce future similar claims, there appear to be significant barriers preventing important lessons from being learned. Detailed learning opportunities are available only to the healthcare providers being sued or the expert witnesses employed to analyse the claims. Most practitioners have to rely on indemnifiers' case reports, closed-claim analyses, and ad hoc publications for information. In this review, we suggest ways in which important lessons from litigation could be brought to the attention of all clinicians. Currently, most clinicians are unable to determine whether key components of their practice such as consent, clinical decision-making, and documentation are of an acceptable standard for legal scrutiny. By reporting outcomes of Coroners' inquests, clinical and criminal negligence cases, and referrals to the General Medical Council, it would be hoped that more explicit standards of performance could be derived. Ultimately, this may not only improve patient safety, but protect practitioners from unjustifiable claims. Finally, given the critical importance of experts in the above process, we believe that a system for professional registration and regulation should be explored to ensure that they offer accurate, representative, and unbiased opinions and have the appropriate expertise in the subject matter to be analysed.


Study on leaching of pollutants from vegetable tanning residue.
The processing of heavy leather employs the vegetable tanning method involving use of tan liquor. The solid residue of this vegetable tanning process aggravates the water pollution by means of leaching of tannin and other associatedpollutants. Tannin is a biologically resistant compound causing several problems in animal body. The present study dealt with the pollution hazard arising out of leaching of pollutants from the open dumped vegetable tanning residue by rainfall washing. The concerned pollutants were pH, Chemical Oxygen Demand (COD), tannin,sulfate and chloride concentration. To explore the possible extent of contamination of these pollutants in the leached water, two different masses (2 kg and 3 kg) of tanning residue were employed. The results of the study showed that there was a continuous release of pollutants from the vegetable tanning residue. Moreover, there was no regular variation in various pollutant concentrations in both the cases solely due to non-homogeneity of the residue.


Severe post-burn hyperextension of metatarsophalangeal joints in a child with bilateral foot contracture.
Achieving a stable plantigrade foot after repair of complex post-burn deformities poses a particularly difficult challenge for the foot and ankle surgeon. We report an unusual case of a child with severe bilateral forefoot contracture deformities treated by soft tissue release and lengthening, and conventional wound coverage with split-thickness skin grafting.


Green Synthesis of Novel Polyaniline Nanofibers: Application in pH Sensing.
An optically active polyaniline nanomaterial (PANI-Nap), doped with (S)-naproxen, was developed and evaluated as a potent pH sensor. We synthesized the material in one pot by the addition of the dopant, (S)-naproxen, prior to polymerization, followed by the addition of the oxidizing agent (ammonium persulfate) that causes polymerization of the aniline. This green chemistry approach allowed us to take only 1 h to produce a water-soluble and stable nanomaterial. UV-visible spectroscopy, fluorescence spectroscopy, FT-IR spectroscopy, Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) were used to characterize the designed nanomaterial. This nanomaterial exhibited excellent pH sensing properties and showed long term stability (up to one month) without loss of sensor performance.


Novel 3-Substituted 7-Phenylpyrrolo[3,2-f]quinolin-9(6H)-ones as Single Entities with Multitarget Antiproliferative Activity.
A series of chemically modified 7-phenylpyrrolo[3,2-f]quinolinones was synthesized and evaluated as anticancer agents. Among them, the most cytotoxic (subnanomolar GI50 values) amidic derivative 5f was shown to act as an inhibitor of tubulin polymerization (IC50, 0.99 μM) by binding to the colchicine site with high affinity. Moreover, 5f induced cell cycle arrest in the G2/M phase of the cell cycle in a concentration dependent manner, followed by caspase-dependent apoptotic cell death. Compound 5f also showed lower toxicity in nontumoral cells, suggesting selectivity toward cancer cells. Additional experiments revealed that 5f inhibited the enzymatic activity of multiple kinases, including AURKA, FLT3, GSK3A, MAP3K, MEK, RSK2, RSK4, PLK4, ULK1, and JAK1. Computational studies showed that 5f can be properly accommodated in the colchicine binding site of tubulin as well as in the ATP binding clefts of all examined kinases. Our data indicate that the excellent antiproliferative profile of 5f may be derived from its interactions with multiple cellular targets.


Effects of anthropogenic developments on common raven nesting biology in the West Mojave Desert.
Subsidized predators may affect prey abundance, distribution, and demography. Common Ravens (Corvus corax) are anthropogenically subsidized throughout their range and, in the Mojave Desert, have increased in number dramatically over the last 3-4 decades. Human-provided food resources are thought to be important drivers of raven population growth, but human developments add other features as well, such as nesting platforms. From 1996 to 2000, we examined the nesting ecology of ravens in the Mojave Desert, relative to anthropogenic developrhent. Ravens nested disproportionately near point sources of food and water subsidies (such as towns, landfills, and ponds) but not near roads (sources of road-killed carrion), even though both sources of subsidy enhanced fledging success. Initiation of breeding activity was more likely when a nest from the previous year was present at the start of a breeding season but was not affected by access to food. The relative effect of environmental modifications on fledging success varied from year to year, but the effect of access to human-provided resources was comparatively consistent, suggesting that humans provide consistently high-quality breeding habitat for ravens. Anthropogenic land cover types in the desert are expected to promote raven population growth and to allow ravens to occupy parts of the desert that otherwise would not support them. Predatory impacts of ravens in the Mojave Desert can therefore be considered indirect effects of anthropogenic development.


L-proline is essential for the intracellular differentiation of Trypanosoma cruzi.
Using as the host cell, a proline-requiring mutant of Chinese hamster ovary cell (CHO-K1), it was possible to arrest the differentiation of amastigote forms of Trypanosoma cruzi at the intermediate intracellular epimastigote-like stage. Complete differentiation to the trypomastigote stage was obtained by addition of L-proline to the medium. This effect was more pronounced using the T. cruzi CL-14 clone that differentiates fully at 33 degrees C (permissive temperature) and poorly at 37 degrees C (restrictive temperature). A synchronous differentiation of T. cruzi inside the host-cell is then possible by temperature switching in the presence of proline. It was found that differentiation of intracellular epimastigotes and trypomastigote bursting were proline concentration dependent. The intracellular concentration of proline was measured as well as the transport capacity of proline by each stage of the parasite. Amastigotes have the highest concentration of free proline (8.09 +/- 1.46 mM) when compared to trypomastigotes (3.81 +/- 1.55) or intracellular epimastigote-like forms (0.45 +/- 0.06 mM). In spite of having the lowest content of intracellular free proline, intracellular epimastigotes maintained the highest levels of L-proline transport compared to trypomastigotes and intracellular amastigotes, providing evidence for a high turnover for the L-proline pool in that parasite stage. This is the first report to establish a relationship between proline concentration and intracellular differentiation of Trypanosoma cruzi in the mammalian host.


HIV and employment.
According to 2009 statistics, the human immunodeficiency virus (HIV) infected an estimated 86,500 individuals within the UK, although around one-quarter were unaware of their infection. In the majority of cases, it is now considered a long-term controllable but incurable infection. Indeed, most HIV-positive individuals are able to work. Employment is across most, if not all, workforce sectors and protection against workplace discrimination is provided by the Equality Act 2010. Issues including confidentiality, workplace adjustments, vaccinations and travel restrictions may be relevant to the occupational health of HIV-positive workers. There are special considerations concerning HIV-infected health care workers, including avoidance of performing exposure-prone procedures. Prevention of HIV acquisition in the workplace is relevant to a diverse range of occupational environments, and HIV post-exposure prophylaxis should be considered after potential HIV exposure incidents. If a worker contracts HIV by occupational means, financial help may be available.


Immunoglobulin classes of antibodies to Aspergillus fumigatus in patients with pulmonary aspergillosis.
An indirect immunofluorescence test was used to determine the titre and immunoglobulin classes of antibodies to Aspergillus fumigatus in human serum. In 15 patients with aspergillosis, significant titres of IgG but not IgA or IgM antibodies were found. The IgG, IgA and IgM fractions of serum from 2 patients with aspergillosis were separated. This confirmed that antibodies to A. fumigatus reside in highest titre in the IgG fraction. Precipitating antibodies to A. fumigatus in these patients also belonged to the IgG class of immunoglobulin.


Optical properties of hair: effect of treatments on luster as quantified by image analysis.
Image analysis has been employed to measure the luster of hair simulated by light reflected from a curved hair tress. Hair samples (up to four) were mounted side-by-side in a special sample holder in the form of a cylinder and illuminated by a uniform beam of white light. Digital images of hair tresses were captured with a high-resolution camera and were analyzed by scanning across highlighted and dark areas of the resultant image using image analysis software with developed macros. Plots, similar to goniophotometric scattering curves, were used to calculate luster values according to previously published work by Nickerson, Stamm, and Reich-Robbins. Both the Stamm and Reich-Robbins approaches were found to give similar results, while the Nickerson gloss parameter exhibited less sensitivity to hair modification with cosmetic ingredients. The procedure was employed to assess the luster of natural white, light blonde, light brown, medium brown, and dark brown hair, and revealed an increase in luster indices in proportion to an increase in fiber pigmentation. Cosmetic oils such as phenyl trimethicone, amodimethicone, and castor oil were also found to increase the luster of hair as a result of the change in contrast between specular and diffuse reflection. Styling resins such as butyl ester of PVM/MA copolymer, vinyl caprolactam/PVP/dimethylaminoethyl methacrylate copolymer, and isobutylene/ethylmaleimide/hydroxyethylmaleimide copolymer were shown to increase hair gloss by a similar mechanism, as evidenced by calculated higher values of the Stamm and Reich-Robbins luster parameters. An effect of hair dulling by deposition of micronized ZnO at various concentrations, as well as by synthetic sebum, is also discussed.


Actions of identified neuromodulatory neurons in a simple motor system.
Recent work on neurons that release slow neuromodulators has revealed important generalities about the roles played by neuromodulation in motor systems. Activity of these cells can affect the cellular and synaptic properties of central pattern generating circuits, orchestrating new variations of motor patterns and sometimes coordinating their outputs with other motor patterns. Many modulatory neurons use multiple transmitters to evoke both fast and slow synaptic responses of various types in different target cells. Some modulatory cells can have a mediating as well as a modulating role, simultaneously acting as sensory neurons or components of another pattern generating circuit.


[Culture supernatants of lymphocytes from different lymphoid tissues induce transdifferentiation of Caco2 cells into M-like cells].
To establish the microfold (M)-like cell model in vitro and identify M-like cells through detecting the capacity of transporting fluorescent beads and the levels of the associated genes, and to observe the effects of lymphocyte culture supernatants stimulated by concanavalin A (Con A) from different lymphoid tissues on the differentiation of Caco2 cells into M-like cells. The isolated lymphocytes of Peyer's patch (PP), mesenteric lymph node (MLN) and spleen (Sp) were incubated with 3 μg/mL Con A for 3 days. The culture supernatants were collected and co-cultured with Caco2 cells. The fluorescent bead suspension was added into the upper compartment of the Transwell™ inserts, and then basolateral solutions were then sampled and analyzed. The number of transported fluorescent beads was measured by flow cytometry. The expressions of M-like cells-associated genes, such as chemokine (C-C motif) ligand 20 (CCL20), claudin4 (CLDN4), tumor necrosis factor receptor superfamily member 9 (TNFRSF9), and Spi-B were detected by reverse transcription PCR. Compared with blank control group, the number of fluorescent beads transported by induced Caco2 cells and the levels of CCL20, CLDN4, TNFRSF9 and Spi-B mRNAs significantly increased in induced Caco2 cells treated with the culture supernatants of lymphocytes from PP, MLN and Sp. After Con A stimulation, the number of fluorescent beads transported by induced Caco2 cells and the levels of CCL20, CLDN4, TNFRSF9 and Spi-B mRNAs were higher than those in the unstimulated group. The lymphocyte culture supernatants stimulated or unstimulated by Con A can induce the transdifferentiation of Caco2 cells into M-like cells.


Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma.
To report long-term efficacy and safety data for everolimus for the treatment of subependymal giant cell astrocytoma (SEGA) in patients with tuberous sclerosis complex (TSC). This was an open-label extension phase of a prospective, phase 1-2 trial (NCT00411619) in patients ≥3 years of age with SEGA associated with TSC. Patients received oral everolimus starting at 3 mg/m2 per day and subsequently titrated, subject to tolerability, to attain whole blood trough concentrations of 5-15 ng/mL. Change in SEGA volume, seizures, and safety assessments were the main outcome measures. Of 28 patients enrolled, 25 were still under treatment at the time of analysis. Median dose was 5.3 mg/m2/day and median treatment duration was 34.2 months (range 4.7-47.1). At all time points (18, 24, 30, and 36 months), primary SEGA volume was reduced by ≥30% from baseline (treatment response) in 65%-79% of patients. All patients reported ≥1 adverse event (AE), mostly grade 1/2 in severity, consistent with that previously reported, and none led to everolimus discontinuation. The most commonly reported drug-related AEs were upper respiratory infections (85.7%), stomatitis (85.7%), sinusitis (46.4%), and otitis media (35.7%). No drug-related grade 4 or 5 events occurred. Everolimus therapy is safe and effective for longer term (median exposure 34.2 months) treatment of patients with TSC with SEGA. This study provides Class III evidence that everolimus, titrated to trough serum levels of 5-15 ng/mL, was effective in reducing tumor size in patients with SEGA secondary to TSC for a median of 34 months.


Proton pump activation in stimulated parietal cells is regulated by gastric acid secretory capacity: a human study.
Under normal physiological conditions, gastric acid production is controlled by a negative feedback mechanism. Proton pump inhibitors, such as pantoprazole, inhibit gastric acid secretion by irreversibly binding and inactivating luminally active hydrogen potassium ATPase. Recovery of acid production after treatment with a proton pump inhibitor is driven by new pump synthesis, activation of existing cytoplasmic pumps, or reversal of proton pump inhibition. The authors measured the time course of the inhibition and recovery of acid secretion in healthy volunteers following intravenous administration of pantoprazole to determine the rate of proton pump activation under maximally stimulated conditions. Gastric acid production was measured in 27 Helicobacter pylori negative healthy volunteers (mean age = 31 +/- 7 years; 17 men, 10 women) who received single doses of intravenous pantoprazole (20, 40, 80, or 120 mg) in the presence of a continuous intravenous infusion of 1 ug/kg/h of pentagastrin. From the time profile of acid secretion, the authors described the rate of change of acid output using an irreversible pharmacodynamic response model represented by the equation dR/dt = -k x R x Cpanto + Ln2/PPR x (Ro-R) and correlated the parameter values with demographic factors and gastric acid measurements. Mean stimulated acid output secretion was 21.6 +/- 18.4 mEq/h (range: 1.6-90.5) prior to the administration of pantoprazole and remained steady for 25 hours after placebo administration. Intravenous pantoprazole inhibited acid output in a dose-response fashion, with maximal inhibition (99.9%) occurring after an 80 mg dose. Mean proton pump recovery time was 37.1 +/- 21.0 hours (range: 6.7-75), and recovery was independent of the dose of pantoprazole. There was no association noted between proton pump recovery time and gender, age, race, body weight, or pantoprazole dose. However, there was an inverse correlation between acid output during baseline stimulation and recovery of acid secretion. Mean proton pump recovery time in stimulated normal human volunteers was 37.1 +/- 21.0 hours, with a range of 6.7 to 75 hours. The authors hypothesize that there may be a normal homeostatic mechanism that maintains acid secretory capability within a normal range by altering the rate of proton pump activation dependent on the individual's parietal cell mass. Abnormalities of this process may be responsible for the development of acid peptic disease in susceptible individuals.


Estrogen suppresses brain mitochondrial oxidative stress in female and male rats.
Mitochondria are a major source of reactive oxygen species (ROS) and oxidative stress, key contributors to aging and neurodegenerative disorders. We report that gonadal hormones influence brain mitochondrial ROS production in both females and males. Initial experiments showed that estrogen decreases mitochondrial superoxide production in a receptor-mediated manner, as measured by MitoSOX fluorescence in differentiated PC-12 cells. We then assessed in vivo effects of gonadal hormones on brain mitochondrial oxidative stress in female and male rats. Brain mitochondria were isolated to measure a functional indicator of ROS, i.e., activity of the ROS-sensitive mitochondrial enzyme, aconitase. Gonadectomy of both males and females caused a decrease in aconitase activity, suggesting that endogenous gonadal hormones influence mitochondrial ROS production in the brain. In vivo treatment of gonadectomized animals with testosterone or dihydrotestosterone (DHT) had no effect, but estrogen replacement significantly increased aconitase activity in brain mitochondria from both female and male rats. This indicates that estrogen decreases brain mitochondrial ROS production in vivo. Sex hormone treatments did not affect protein levels of brain mitochondrial uncoupling proteins (UCP-2, 4, and 5). However, estrogen did increase the activity, but not the levels, of manganese superoxide dismutase (MnSOD), the mitochondrial enzyme that catalyzes superoxide radical breakdown, in brain mitochondria from both female and male rats. Thus, in contrast to the lack of effect of androgens on mitochondrial ROS, estrogen suppression of mitochondrial oxidative stress may influence neurological disease incidence and progression in both females and males.


Multimodal treatment of a child with schizophrenia.
A case is presented of a five-year-old boy with schizophrenia who received both art and play therapy within a multimodal therapeutic program. The course of the two therapies is presented followed by a discussion of the similarities and differences of the techniques, but also noting the complementary and synergistic results.


A guide to post-mortem examination procedure in mouse models.
The main objective of a post mortem is to identify, at a macroscopic level, any anatomical features that characterise mutant or sick mice and to describe lesions contributing to morbidity and mortality. Tissues collected for subsequent examination require appropriate handling and preservation to prevent deterioration. Therefore, efficient routine procedures are essential to facilitate histology and to ensure high-quality samples. In addition, optimised techniques minimise data loss from damaged samples reducing the numbers of animals used and supporting the 3Rs principle of reduction. Here, we describe an optimised method for tissue collection in the mouse. Training tips and points for caution are included.


[Capabilities of remote laser homeostasis of the conjunctiva and sclera].
During some eye surgeries, a need for hemostasis can arise in order to prevent bleeding. To determine the optimal settings for remote laser action of Nd:YAG laser with a wavelength of 1.44 µm on the conjunctival and episcleral vessels of the eye to stop bleeding, as well as for preemptive anemisation of tissue prior to performing a surgical incision. The characteristics of the laser impact on vessels of the conjunctiva and sclera were studied clinically while conducting surgeries on 36 patients for cataract, glaucoma and excision of pterygium. The best mode of operation of Nd:YAG laser for remote laser anaemisation of the area of planned cut were 1.44 µm wavelength with 5 Hz frequency and energy of 100 mJ. Remote hemostasis can be achieved with the following settings for energy parameters: for pulse frequency of 5 Hz - pulse energy from 150 to 200 mJ; for pulse frequency of 10 Hz and 15 Hz - energy from 100 to 150 mJ; for pulse frequency of 25 Hz - energy not exceeding 100 mJ. No scar remained after the action of 1.44-µm Nd:YAG laser, and recanalization of individual vessels was possible.


Phytochemical quantification and total antioxidant capacities of emmer (Triticum dicoccon Schrank) and einkorn (Triticum monococcum L.) wheat landraces.
In this study, samples of 18 ancient wheat (12 emmer, 6 einkorn) and 2 bread wheat varieties grown in different regions of Turkey were examined for their total phenolics and flavonoids, phenolic acids, lutein, total yellow pigment, and total radical scavenging capacities against ABTS cation. Results showed that health beneficial phytochemicals and total antioxidant capacities were generally significantly different in emmer and einkorn wheat groups. Remarkably higher total antioxidant activity (18.31 +/- 1.31 micromol Trolox equiv/g), total phenolics (6.33 +/- 0.98 micromol gallic acid equiv/g), ferulic acid (662.95 +/- 61.07 microg/g), and flavonoids (1.61 +/- 0.34 micromol catechin equiv/g) content were detected in emmer wheat samples (n = 12), suggesting that they may have high potential for utilization as a novel grain, rich in natural antioxidants. In addition, quite high levels of lutein (7.33 +/- 2.43 microg/g) of einkorn samples (n = 6) hold the potential of developing high-lutein bakery products to considerably raise the dietary intake of carotenoids. These findings for ancient wheat varieties are considered to be very useful in breeding programs for selecting and breeding wheat varieties for higher concentration and better composition of health-beneficial phytochemicals.


[Efficacy of Venetoclax Plus Azacitidine in Relapsed/Refractory Acute Myeloid Leukemia Patients with FLT3-ITD Mutation].
To explore the efficacy of venetoclax (VEN) plus azacitidine (AZA) in patients with FLT3-ITD mutated relapsed/refractory acute myeloid leukemia (FLT3-ITDmut R/R AML) and analyze the molecular genetic characteristics of the patients. Clinical baseline characteristics and follow-up data of 16 R/R AML patients treatd with VEN plus AZA in the hematology department of Shenzhen Second People's Hospital from November 2018 to April 2021 were collected. Leukemia related genes were detected by next-generation sequencing(NGS) or PCR. The relationship between the efficacy of VEN plus AZA and molecular genetics characteristics of patients with FLT3-ITDmut R/R AML were analyzed. 14.3% (1/7) of the patients in FLT3-ITDmut group and 22.2% (2/9) of the patients in FLT3-ITDwt group achieved complete remission (CR)/CR with incomplete blood count recovery (CRi), respectively, with no significant difference (P=0.69). There was no significant difference in overall response rate (ORR) (CR/CRi+PR) between FLT3-ITDmut group and FLT3-ITDwt group [42.9%(3/7) vs 44.4%(4/9), P=0.95], too. The median overall survival (OS) time of FLT3-ITDmut patients was significantly shorter than that of FLT3-ITDwt patients (130 vs 300 days, respectively) (P =0.02). Co-existing mutations of FLT3-ITD and IDH1 were detected in one patient who achieved CR. Co-existing mutations of FLT3-ITD and SF3B1 were found in one patient who achieved PR. Three FLT3-ITDmut R/R AML patients accompanied with NPM1 mutation had no response to VEN plus AZA. VEN plus AZA showed a certain effect on patients with FLT3-ITDmut R/R AML. To improve OS of the patients, bridging transplantation is need. IDH1 and SF3B1 mutations might predict that patients with FLT3-ITDmut R/R AML have treatment response to VEN plus AZA, while the combination of NPM1 mutation may indicate poor response.


Kinetics of gelation and thermal sensitivity of N-isobutyryl chitosan hydrogels.
N-Acylation of chitosan with carboxylic anhydrides in dilute acetic acid/methanol has been a well documented strategy to selectively modify chitosan. Although this reaction is known to lead to irreversible gel formation, the kinetics and mechanism of this process have not so far been addressed. To this purpose, gel formation during the N-isobutyrylation of chitosan was investigated as a function of the reaction stoichiometry (R), chitosan concentration, and temperature by small deformation oscillatory rheology. Gel formation follows closely the chemical reaction and it proceeds predominantly under second-order kinetics as established from the dependence of critical gel time, t(gel), on R and concentration. The activation energy value derived from t(gel) vs 1/T data (E(a) = 68.29 +/- 1.80 kJ/mol) was almost identical to values reported for the chitosan N-acetylation reaction in previous studies. An excess isobutyric anhydride is suggested to be necessary for nucleation and hydrophobic association. The potential application of N-isobutyrylchitosan (NIBC) hydrogels in the design of thermally sensitive materials is also demonstrated.


[Percutaneous bursting of the pulmonary valve].
In a 25-year-old female patient with pulmonary valve stenosis valvuloplasty could be successfully performed using a balloon catheter inserted via the femoral vein. Balloon measurements were 2 cm width and 3 cm length, the required pressure was 5 atm. There was a decrease of the pressure gradient form 60 to 25 mm Hg, systolic right ventricular pressure decreased from 88 to 50 mm Hg. Besides transluminal angioplasty of coronary stenoses and non-surgical occlusion of patent ductus arteriosus thus a further catheter technique for treatment of organic heart disease has become available, being able to replace surgery.


Third molar periodontal pathology and caries in senior adults.
This study was designed to assess the prevalence at enrollment and incidence over 36 months of periodontal pathology and caries affecting third molars in a community-based study of people over the age of 65 years in North Carolina. A sub-sample of 818 subjects with dental examinations taken from the Piedmont 65+ Study was available for analysis. All visible teeth were examined. Periodontal probing (PD) measures were taken at 2 sites, mesiobuccal and buccal/facial. Clinical data on caries experience were collected by visual-tactile examination. At enrollment, 342 subjects had at least 1 visible third molar that could be examined. PD measures were available for 276 of these same subjects. The significance of comparisons between third molars and nonthird molars were determined by chi(2) tests and the statistical significance was set at .05. Most of the 342 subjects with at least 1 visible third molar were female (57%) or African American (63%). Mean age was 73 years (SD 5.5 years). Of the 197 subjects with caries experience, third molars were affected in 49% of subjects, less than the 87% in nonthird molars. Third molar caries experience was associated with caries experience on nonthird molar teeth (P < .01). Clinical attachment level (CAL) greater than 3 mm was detected at enrollment in third molars in 68% of subjects, and in nonthird molars in 96%. With one exception, CAL greater than 3 mm in third molars was associated with CAL greater than 3 mm elsewhere in the mouth. Few subjects (17%) had clinical evidence of both caries and periodontal pathology affecting third molars. In this older population of individuals with third molars, 21% were free of periodontal pathology or caries experience. Data on the prevalence of third molar periodontal pathology and third molar caries experience in an elderly population should be useful to both clinicians and their younger patients when considering the merits of retaining or removing third molars with no evidence of pathology.


Seasonal variation of peptidase activities in the reproductive tract of Crotalus durissus terrificus.
Seasonal quantitative patterns of acid (APA), basic (APB), puromycin-sensitive (APN-PS) and puromycin-insensitive neutral (APN-PI), cystyl (CAP), dipeptidyl IV (DPPIV), type-1 pyroglutamyl (PAP-I) and prolyl-imino (PIP) aminopeptidases and prolyl oligopeptidase (POP) activities in soluble (SF) and solubilized membrane-bound (MF) fractions from ductus deferens, vagina and uterus were studied to evaluate their relationships with the reproductive cycle and the extensive long-term spermatozoa storage (LTSS) of the Neotropical rattlesnake Crotalus durissus terrificus. APB, PIP and POP were detected only in SF, while other peptidases were detected in SF and MF. APB, APN-PI and APN-PS were predominant in most tissues in all seasons. Peptidase activities had a common pattern of increment during the dry season (winter/autumn), which coincides with the mating period (autumn) and LTSS in the female (winter), as well as the reduction of spermatozoa motility and maintenance of fertilization capacity of spermatozoa. The high CAP activity in the soluble fraction of the vagina during winter, compared to summer (time of parturition) and spring, coincides with the relaxation of this tissue. In the soluble fraction, the low PAP-I activity of the ductus deferens coincided with its high activity in the vagina during the winter; and the inverse occurred in summer, which is consistent with the physiological process of preserving spermatozoon viability. In conclusion, the studied peptidase activities had seasonal and tissue-specific characteristics, which suggest a relevant role in the reproductive physiology of C. d. terrificus.


Saccadic velocity studies in superior oblique palsy.
Eighteen patients (21 eyes) with superior oblique palsy had vertical saccadic velocity measurements in primary gaze, adduction, and abduction. No noticeable difference was found when upward saccades were compared with downward saccades in all fields of gaze. Thus, saccadic velocity studies would not be helpful in the diagnosis of superior oblique palsy.


Metabolic effects of continuous subcutaneous insulin infusion: evidence that a rise and fall of portal vein insulin concentration with each major meal facilitates post-absorptive glycemic control.
Eighteen lean adult volunteers with insulin-requiring diabetes mellitus attempted to achieve normoglycemia using continuous subcutaneous insulin infusion (CSII) or conventional insulin therapy (CIT) in a randomized crossover trial of 68 +/- 2.5 weeks (mean +/- SEM) duration. As reported (Diabetes Care 8: 447-55, 1985) the group with absent to low beta-cell function (C-peptide negative, n = 11) attained mean post-absorptive normoglycemia only during CSII vs CIT (p less than 0.05). Only following CSII was this without change in post-absorptive serum triglyceride concentrations (-4 +/- 5.6 vs 12 +/- 4.7 mg/dl; -0.04 +/- 0.6 vs 0.14 +/- 0.05 mM, p less than 0.05) or body weight (0.01 +/- 0.02 vs 0.05 +/- 0.01 kg/week, p less than 0.05). In the group with glucagon stimulated serum C-peptide 100-400 pmol/L (C-peptide positive) responses to CSII or CIT were equal. As total daily insulin dosage (0.05 +/- 0.04 U/kg/day) was the same under all conditions, to explain the efficacy of CSII, glucoregulatory hormone responses were examined. Pre- and post-test breakfast serum free immunoreactive insulin and plasma glucagon concentrations were essentially unaffected by C-peptide or treatment status. Erythrocyte 125I-insulin binding was decreased in the C-peptide negative group only during CSII (8.6 +/- 0.5 vs 10.1 +/- 0.7%, p less than 0.005); C-peptide positive group receptor binding was consistently low (8.2 +/- 0.8, 8.4 +/- 0.9%). During CIT using intermediate-acting insulin post-lunch peripheral venous insulin failed to rise (p less than 0.05), but in the C-peptide positive group, on the basis of C-peptide responses to breakfast an undetected rise and fall of portal venous insulin was assumed to coincide with each meal. Thus, only during CIT in the C-peptide negative group, which received on average 6.4/wk/subject fewer pre-meal regular insulin boluses (p less than 0.01), was the frequency of meal-related change in portal insulinemia decreased. Consistent meal-related fluctuations in portal insulinemia inherent in CSII hepatocytes sensitized by a post-receptor mechanism to the suppressive effects of insulin on glucose output and thus were indirectly responsible for the observed improvement in glycemic control and lipid metabolism in the C-peptide negative group.


Hepatitis C infection: eligibility for antiviral therapies.
Current treatments of chronic hepatitis C virus (HCV) are effective, but expensive and susceptible to induce significant side effects. To evaluate the proportion of HCV patients who are eligible for a treatment. In a database comprising 1726 viraemic HCV patients, the files of 299 patients who presented to the same hepatologist for an initial appointment between 1996 and 2003 were reviewed. Patients' characteristics were age 43.1 +/- 15.6 years, 53% male and 92% Caucasian. The main risk factors were transfusion (43%) and drug use (22%). Genotypes were mostly genotype 1 (66%), genotype 3 (12%) and genotype 2 (10%). These characteristics were not different from those of the whole series of 1726 patients. A total of 176 patients (59%) were not treated, the reasons for non-treatment being medical contraindications (34%), non-compliance (25%) and normal transaminases (24%). In addition, 17% of patients declined therapy despite being considered as eligible, mainly due to fear of adverse events. Medical contraindications were psychiatric (27%), age (22%), end-stage liver disease (15%), willingness for pregnancy (13%), cardiac contraindication (7%) and others (16%). Only 123 patients (41%) were treated. A sustained viral response was observed in 41%. The treatment was interrupted in 16% for adverse events. The majority of HCV patients are not eligible for treatment. This implies that, with current therapies, only 17% of patients referred for chronic HCV become sustained responders. Some modifications of guidelines could extend the rate of treatment (patients with normal transaminases), but an important barrier remains the patients' and the doctors' fear of adverse events.


Interference with gastrulation during the third week of pregnancy as a cause of some facial abnormalities and CNS defects.
During the third week of pregnancy the human embryo undergoes a major developmental process, gastrulation, during which the two-layered embryo is converted into a three-layered embryo. At the same time, the upper epiblast layer is induced to form the neural plate. Evidence is presented which suggests that interference with this process by genetic, physical, or chemical agents can cause a range of CNS abnormalities and facial abnormalities, including those described as characteristic of the FAS.


Metabolic fingerprinting of dogs with idiopathic epilepsy receiving a ketogenic medium-chain triglyceride (MCT) oil.
Consumption of medium-chain triglycerides (MCT) has been shown to improve seizure control, reduce behavioural comorbidities and improve cognitive function in epileptic dogs. However, the exact metabolic pathways affected by dietary MCT remain poorly understood. In this study, we aimed to identify changes in the metabolome and neurotransmitters levels relevant to epilepsy and behavioural comorbidities associated with the consuming of an MCT supplement (MCT-DS) in dogs with idiopathic epilepsy (IE). Metabolic alterations induced by a commercial MCT-DS in a population of 28 dogs with IE were evaluated in a 6-month multi-centre, prospective, randomised, double-blinded, controlled cross-over trial design. A metabolic energy requirement-based amount of 9% MCT or control oil was supplemented to the dogs' stable base diet for 3 months, followed by the alternative oil for another 3 months. A validated, quantitative nuclear magnetic resonance (NMR) spectroscopy platform was applied to pre- and postprandially collected serum samples to compare the metabolic profile between both DS and baseline. Furthermore, alterations in urinary neurotransmitter levels were explored. Five dogs (30%) had an overall reduction in seizure frequency of ≥50%, and were classified as MCT-responders, while 23 dogs showed a ≤50% reduction, and were defined as MCT non-responders. Amino-acid metabolism was significantly influenced by MCT consumption compared to the control oil. While the serum concentrations of total fatty acids appeared similar during both supplements, the relative concentrations of individual fatty acids differed. During MCT supplementation, the concentrations of polyunsaturated fatty acids and arachidonic acid were significantly higher than under the control oil. β-Hydroxybutyric acid levels were significantly higher under MCT supplementation. In total, four out of nine neurotransmitters were significantly altered: a significantly increased γ-aminobutyric acid (GABA) concentration was detected during the MCT-phase accompanied by a significant shift of the GABA-glutamate balance. MCT-Responders had significantly lowered urinary concentrations of histamine, glutamate, and serotonin under MCT consumption. In conclusion, these novel data highlight metabolic changes in lipid, amino-acid and ketone metabolism due to MCT supplementation. Understanding the metabolic response to MCT provides new avenues to develop better nutritional management with improved anti-seizure and neuroprotective effects for dogs with epilepsy, and other behavioural disorders.


A new anti-H lectin.
The results of serological investigations of a new anti-H lectin obtained from the leaves of Sambucus nigra are presented. In saline extracts the lectin is useful for investigating the ABO secretors' status, A-subgroups and absorption-elution experiments as well.


Assay of serum fibrin degradation products by agglutination-inhibition of coated erythrocytes.
An immunological method for detecting fibrin degradation products by tanned cells agglutination has been standardized. The effects of different variables, such as cell concentration, pH, and length of incubation, and the specificity of the reaction, are described. The method is compared with other immunological techniques.


Involvement of Wnt4 signaling during myogenic proliferation and differentiation of skeletal muscle.
The direct effects of Wnt4 on myogenic proliferation and differentiation of skeletal muscle precursors are examined. Wnt4 cDNA was misexpressed in the presumptive limb fields on the right side of stage 16 chick embryos. Muscle development was evaluated at stage 37 with hematoxylin-eosin staining and immunohistochemical staining for fast and slow types of the myosin heavy chain (MyHC). Overexpression of Wnt4 resulted in up-regulation of Pax7 and MyoD1 expression. The muscle mass showed a significant increase compared with that of the control limb. The area for fast MyHC-expressing cells showed a significant increase, whereas a slight decrease was observed for slow MyHC-expressing cells. Wnt4 acted as a stimulator during myogenic proliferation and differentiation, especially, for fast-type muscle in C2C12 cells. The present results are identical to those of myostatin knockout, suggesting that Wnt4 is acting against myostatin as an antagonizing signal for myostatin.


Non-segmental vitiligo and psoriasis comorbidity - a case-control study in Italian patients.
A recent systematic evaluation of vitiligo and psoriasis comorbidity has not yet been reported in a large series of patients with vitiligo. To investigate the practical/clinical implications in subjects with both vitiligo and psoriasis compared to those with vitiligo alone. This was a case-control study on 463 vitiligo patients in our clinic from March 2008 to April 2011. Medical assessment was performed by dermatologists using the modified Vitiligo European Task Force form. In an univariate analysis, inflammation/pruritus [odds ratio (OR) 2.42, P = 0.03], use of drugs that can induce psoriasis (OR 2.74, P = 0.01), a family history (FH) of psoriasis (OR 2.87, P = 0.02), cardiovascular disease (OR 5.70, P = 0.001), hypertension (OR 4.7, P = 0.006) and type 2 diabetes mellitus (OR 3.87, P = 0.004), were significantly correlated with patients exhibiting vitiligo and psoriasis comorbidity. A trend was found in personal history of cardiovascular disease in patients with both diseases (OR 2.99, P = 0.07). FH of vitiligo was significantly associated with patients having only vitiligo (OR 0.35, P = 0.05). Multivariate analysis demonstrated that inflammation/pruritus in vitiligo macules (OR 2.56, P = 0.047) and a FH of cardiovascular disease (OR 4.07, P = 0.02) were the most significant predictors of patients having both psoriasis and vitiligo, while the presence of organ-specific autoantibodies (OR 0.24, P = 0.007) was significantly associated with patients having only vitiligo. The presence of vitiligo and even mild psoriasis is significantly correlated with a family history of cardiovascular disease, a factor that requires greater attention and follow-up with respect to that necessary for vitiligo patients.


A variable region on the chlorovirus CVK2 genome contains five copies of the gene for Vp260, a viral-surface glycoprotein.
A 22.2-kb variable region near the left end of the chlorovirus CVK2 genome that was previously supposed to be expanded compared to the PBCV-1 genome was characterized. This region contains a tandem array of five gene copies for the Vp260-like protein, a viral-surface glycoprotein. The authentic 104-kDa Vp260 was found to be encoded at another site on the genome and to contain 13 internal tandem repeats of 61-65 amino acids, similar to the prominent Rickettsia surface antigen. The extra copies were also found to retain 10 of the internal repeats, despite the C-terminal deletions or extensions. These extra copies are conserved among chloroviruses isolated in various areas of Japan. By Northern blot analysis, these genes were demonstrated to be expressed late in infection. The proteins are incorporated into virions, as revealed by comparing viral structural proteins between wild-type and deletion mutants. These results indicate that extra copies of Vp260-like proteins encoded in a variable region on the genome may give variations in the surface nature of the chloroviral particles.


Role of radiolabelled leucocyte scintigraphy in patients with a suspicion of prosthetic valve endocarditis and inconclusive echocardiography.
In patients with a suspicion of prosthetic valve endocarditis (PVE), detection of perivalvular infection can be difficult based only on echocardiography. The aim of this retrospective study was to test the interest of radiolabelled leucocyte scintigraphy (LS) for the detection of perivalvular infection in patients with a suspicion of PVE and inconclusive transoesophageal echocardiography (TEE). LS was performed in 42 patients. The results of LS were classified as positive in the cardiac area (intense or mild), or negative. Macroscopical aspects and bacteriology were obtained from patients who underwent cardiac surgery (n = 10). Clinical outcome was collected in patients treated medically (n = 32). Among patients with intense signal with LS who underwent surgery (n = 6), five had an abscess confirmed during intervention and one, post-operatively. Patients with intense accumulation of radiolabelled leucocytes with scintigraphy and treated medically (n = 3) had a poor outcome: death (n = 1); prosthetic valve dehiscence (n = 1); and recurrent endocarditis (n = 1). Among patients with mild activity with LS (n = 5), one patient developed a large prosthetic valve dehiscence during the follow-up. The remaining four patients were treated medically and did not present any recurrent endocarditis after a median follow-up of 14 months. No abscess was detected in patients with negative LS who underwent surgery (n = 4). Among the patients with negative LS treated medically (n = 24), none presented recurrent endocarditis after a mean follow-up of 15 ± 16 months. Patient management was influenced by the results of LS in 12 out of 42 patients (29%). This study suggests that LS is useful for the identification of perivalvular infection in patients with a suspicion of PVE and inconclusive TEE.


Idiopathic granulomatous vulvitis.
A 20-year-old woman initially presented with clinical evidence of an acute vulval inflammatory disorder incorrectly diagnosed as a Bartholin's abscess. Prolonged healing associated with infection followed attempts to incise and biopsy the area. Over a decade the condition has followed a chronic course with exacerbations and remissions and the vulva has become progressively more swollen and distorted. Lymphangiomas have developed. Histology showed non-necrotizing granulomas. Investigations for Crohn's disease and sarcoidosis were negative. Prednisone resulted in improvement during acute inflammatory episodes.


The effect of active immunization against adrenocorticotropic hormone on cortisol, beta-endorphin, vocalization, and growth in pigs.
Because the poor growth performance of intensively housed pigs is associated with increased circulating glucocorticoid concentrations, we investigated the effects of glucocorticoid suppression by inducing a humoral immune response to ACTH on physiological and production variables in growing pigs. Grower pigs (28.6 +/- 0.9 kg) were immunized with amino acids 1 through 24 of ACTH conjugated to ovalbumin and suspended in diethylaminoethyl (DEAE) dextran-adjuvant or adjuvant alone (control) on d 1, 28, and 56. The ACTH-specific antibody titers generated suppressed increases in cortisol concentrations on d 63 in response to an acute stressor (P = 0.002; control = 71 +/- 8.2 ng/mL; ACTH-immune = 43 +/- 4.9 ng/mL) without altering basal concentrations. Plasma beta-endorphin concentrations were also increased (P < 0.001) on d 63 (control = 18 +/- 2.1 ng/mL; ACTH-immune = 63 +/- 7.3 ng/mL), presumably because of a release from negative feedback on the expression of proopiomelanocortin in pituitary corticotropes. Immunization against ACTH did not alter ADG (P = 0.120; control = 1,077 +/- 25; ACTH-immune = 1,143 +/- 25 g) or ADFI (P = 0.64; control = 2,719 +/- 42; ACTH-immune = 2,749 +/- 42 g) and did not modify behavior (P = 0.681) assessed by measuring vocalization in response to acute restraint. In summary, suppression of stress-induced cortisol responses through ACTH immunization increased beta-endorphin concentrations, but it did not modify ADG, ADFI, or restraint vocalization score in growing pigs.


Incidental intestinal malrotation in an adult: Midgut volvulus.
Intestinal malrotation is a developmental anomaly characterized by a midgut fixation disorder and failure to complete its normal fetal rotation around the superior mesenteric artery inside the peritoneal cavity. Malrotation is a rare cause of mechanical intestinal obstruction in adults. It may manifest as an emergency condition or with chronic abdominal symptoms. Although its diagnosis remains difficult, early diagnosis and treatment usually yield favorable outcomes. Intestinal malrotation rarely has an asymptomatic course, in which the diagnosis is usually made incidentally. Multislice computed tomography is quite helpful for making a correct diagnosis. In this study, we reported a 56-year-old patient incidentally who was detected to have intestinal malrotation and was managed symptomatically after presenting at our clinic with signs and symptoms of intestinal obstruction; we also provided a discussion of the relevant literature.


Memory formation: from network structure to neural dynamics.
Understanding the neural correlates of brain function is an extremely challenging task, since any cognitive process is distributed over a complex and evolving network of neurons that comprise the brain. In order to quantify observed changes in neuronal dynamics during hippocampal memory formation, we present metrics designed to detect directional interactions and the formation of functional neuronal ensembles. We apply these metrics to both experimental and model-derived data in an attempt to link anatomical network changes with observed changes in neuronal dynamics during hippocampal memory formation processes. We show that the developed model provides a consistent explanation of the anatomical network modifications that underlie the activity changes observed in the experimental data.


Neuroregenerative strategies after radical prostatectomy.
Patients with erectile dysfunction (ED) following radical prostatectomy (RP) continue to present to practicing urologists. Although nerve-sparing RP has decreased the rates of ED significantly, new therapies for cavernosal nerve protection and recovery are now being developed. This report discusses the many agents available in neuroregeneration and neuroprotection to aid in the recovery of erectile function. Multiple agents and strategies have been used for neuroprotection and neuroregeneration of the cavernosal nerve following RP and in nerve injury models. Many of these agents display promise for the treatment of impotence. Early treatment for patients recovering from RP is becoming the standard of care. Natural recovery of erections may take as long as 18 to 24 months post RP; however, treatment plans may reduce the time to erectile recovery.


Interaction between BMSCs and EPCs promotes IUA angiogenesis via modulating PI3K/Akt/Cox2 axis.
Intrauterine adhesion (IUA) is a common disease among women after uterus operation. BMSCs are commonly used as a therapeutic agent for IUA treatment, but the underlying mechanism is not fully delineated. Here we showed that BMSCs co-cultured with EPCs promotes proliferative ability and decreases apoptosis ratio of BMSCs and EPCs. In addition, BMSCs promote the differentiation of EPCs into vascular endothelial cells, and BMSCs derived epithelial cells are also induced by EPCs. We also found that the levels of Collagen Type I, vascular endothelial growth factor (VEGF), granulocyte-macrophage colony stimulating factor (GM-CSF) and bone morphogenetic protein (BMP-2) are significantly increased in the co-culturing system comparing to those of the BMSCs or EPCs alone group. Of note, PI3K/Akt/Cox2 axis is activated in the co-culturing system and LY294002 abrogates the co-culturing system's effects on cell proliferation, apoptosis and cytokines secretion, which are reversed by synergistically overexpressing Cox2. In conclusion, our in vitro experiments proved that the interaction of BMSCs and EPCs might promote angiogenesis and alleviate IUA pathogenesis by regulating PI3K/Akt/Cox2 axis mediated modulation of cell apoptosis, proliferation, differentiation and angiogenesis-associated cytokines secretion.


Evidence of Oxygen Activation in the Reaction between an N-Heterocyclic Carbene and M3N@Ih(7)-C80: An Unexpected Method of Steric Hindrance Release.
We herein demonstrate for the first time the unexpected oxygen-involving reaction between M3N@Ih(7)-C80 (M = Sc, Lu) and 1,3-bis(diisopropylphenyl)imidazol-2-ylene (1). By introducing a tiny amount of oxygen into the reaction, unprecedented products (2a for Sc3N@C80 and 3a for Lu3N@C80) with the normal carbene center C2 singly bonded to a triple hexagonal junction (THJ) cage carbon together with an oxygen atom bridging the same THJ carbon atom and a neighboring carbon atom forming an epoxy structure are obtained. In situ mechanism study, in combination with theoretical calculations, reveals that the bond-breaking peroxidation facilitates the formation of the unexpected products 2a and 3a, providing new insight into fullerene chemistry.


A proposal for a collecting mirror assembly for large divergence x-ray sources.
We propose a new type of collecting mirror assembly (CMA) for x rays, which will enable us to build a powerful optical system for collecting x rays from large divergence sources. The CMA consists of several mirror sections connected in series. The angle of each section is designed so that the x rays reflected from it are parallel to the x rays directly incident on the following sections. A simplified CMA structure is designed and applied to the Al-Kα emission line. It is estimated that by using the CMA the number of x rays detected could be increased by a factor of about 2.5.


Saccadic peak velocity sensitivity to variations in mental workload.
For research and applications in the field of (neuro)ergonomics, it is of increasing importance to have reliable methods for measuring mental workload. In the present study we examined the hypothesis that saccadic eye movements can be used for an online assessment of mental workload. Saccadic main sequence (amplitude, duration and peak velocity) was used as a diagnostic measure of mental workload in a virtual driving task with three complexity levels. We tested 18 drivers in the SIRCA driving simulator while their eye movements were recorded. The Wickens' multiple resources model was used as theoretical framework. Changes in mental workload between the complexity levels were evaluated multidimensionally, using subjective rating, performance in a secondary task, and other behavioral indices. Saccadic peak velocity decreased (7.2 visual degrees/s) as the mental workload increased, as measured by scores of mental workload test (15.2 scores) and the increase of the reaction time on the secondary task (46 ms). Saccadic peak velocity is affected by variations in mental workload during ecologically valid tasks. We conclude that saccadic peak velocity could be a useful diagnostic index for the assessment of operators' mental workload and attentional state in hazardous environments.


Adapted methods for scanning electron microscopy (SEM) in assessment of human sperm morphology.
Infertility is a widespread problem, and in some cases, the routine basic semen analysis is not sufficient to detect the cause of male infertility. The use of the scanning electron microscope (SEM) could provide a detailed insight into spermatozoa morphology, but it requires specific sample preparation techniques. The purpose of this study was to select, adjust, and optimize a method for the preparation of spermatozoa samples prior to SEM analysis, and to establish the protocol required for its use in clinical practice. We examined sperm samples of 50 men. The samples were fixed with modified iso-osmolar aldehyde solution followed by osmium post-fixation. In the first method, dehydration of the cells and subsequent critical point drying (CPD) were performed on a coverslip. In the second method, the samples were dehydrated in centrifuge tubes; hexamethyldisilazane (HMDS) was used as a drying agent instead of CPD, and the samples were air-dried. The third procedure was based on a membrane filter. The samples were dehydrated and dried with HMDS in a Gooch crucible, continuously, without centrifugation or redispersion of the sample. Our results showed that the fixation with modified iso-osmolar aldehyde solution followed by osmium post-fixation, and combined with dehydration and CPD on a coverslip, is the most convenient procedure for SEM sample preparation. In the case of small-size samples or low sperm concentration, dehydration and drying with HMDS on the membrane filter enabled the best reliability, repeatability, and comparability of the results. The presented procedures are suitable for routine use, and they can be applied to confirm as well as to correct a diagnosis.


Comparison of the effectiveness and safety of formoterol versus salmeterol in the treatment of patients with asthma: A systematic review and meta-analysis.
Formoterol and salmeterol are two long-acting β2-agonists given by inhalation, with bronchodilating effects lasting for at least 12 h after a single administration. Formoterol has a faster onset of action compared with salmeterol. The aim of this study was to perform a systematic review and meta-analysis on the data published from previous review in order to calculate pooled estimates of effectiveness and safety assessment of formoterol and salmeterol in treatment of patients with asthma. In this study, we conducted an electronic search for medical citation databases including Cochrane, PubMed, Scopus, PsycInfo, and IranMedex. Besides manual search of the databases that record randomized clinical trials, conference proceedings, and journals related to asthma were included. Studies were evaluated by two independent people based on inclusion and exclusion criteria, and the common outcomes of studies were entered into the RevMan 5.0.1 software, after evaluation of studies and extraction of data from them; and in cases where there were homogeneous studies, meta-analysis was performed, and for heterogeneous studies, the results were reported qualitatively. Of the 1539 studies initially found, 13 were included in the study. According to the meta-analysis conducted, no significant difference was found between the inhalation of formoterol 12 μg and salmeterol 50 μg in the two outcomes of mean forced expiratory volume 1 s (FEV1), 12 h after inhalation of medication and Borg score (A frequently used scale for quantifying breathlessness) after inhalation of medication. In addition, salmeterol was more effective than formoterol in the two outcomes of percent decrease in FEV1 after inhalation of methacholine and the number of days without an attack. Since the two outcomes of FEV1 30-60 min after inhalation of medication and morning peak expiratory flow after inhalation of medication were heterogeneous, they had no meta-analysis capabilities, and its results were reported qualitatively. The data from included studies shows that, more efficacy has been achieved with Salmeterol, especially in some outcomes such as the percent decrease in FEV1 after inhalation of Methacholine, and the number of days without an attack; and therefore, the administration of Salmeterol seems to be beneficial for patients, compared with Formoterol.


Discovery of a potent cyclooxygenase-2 inhibitor, S4, through docking-based pharmacophore screening, in vivo and in vitro estimations.
Cyclooxygenase (COX; EC: 188.8.131.52), the key enzyme in prostaglandin production in the human body, is a major pharmacological target for developing anti-inflammatory agents. Nonsteroidal anti-inflammatory drugs exhibit anti-inflammatory and analgesic activities when inhibiting COX-2 but cause gastrointestinal toxicity and other side effects because of concurrent inhibition of COX-1. Thus, potent and safe inhibitors against COX-2 are urgently required. We constructed a novel docking-based pharmacophore model for screening selective COX-2 inhibitors and discovered compounds S1, S2, S3, and S4, which apparently inhibit COX-2. Particularly, S4 inhibits COX-2 in vitro and shows a potent anti-inflammatory effect in vivo without cytotoxicity. Molecular docking analyses revealed that S4 interacted satisfactorily with the active site of COX-2 but not with that of COX-1. This reveals that S4 more specifically inhibits COX-2 and has potential for application in developing anti-inflammatory and anticancer agents.


Construction of Two mCherry Plasmids (pXG-mCherry) for Transgenic Leishmania: Valuable Tools for Future Molecular Analysis.
Leishmania is the causative agent of leishmaniasis, a neglected tropical disease that affects more than 12 million people around the world. Current treatments are toxic and poorly effective due to the acquisition of resistance within Leishmania populations. Thus, the pursuit for new antileishmanial drugs is a priority. The available methods for drug screening based on colorimetric assays using vital dyes are time-consuming. Currently, the use of fluorescent reporter proteins is replacing the use of viability indicator dyes. We have constructed two plasmids expressing the red fluorescent protein mCherry with multiple cloning sites (MCS), adequate for N- and C-terminal fusion protein constructs. Our results also show that the improved pXG-mCherry plasmid can be employed for drug screening in vitro. The use of the red fluorescent protein, mCherry, is an easier tool for numerous assays, not only to test pharmacological compounds, but also to determine the subcellular localization of proteins.


Evolution of correlated multiplexity through stability maximization.
Investigating the relation between various structural patterns found in real-world networks and the stability of underlying systems is crucial to understand the importance and evolutionary origin of such patterns. We evolve multiplex networks, comprising antisymmetric couplings in one layer depicting predator-prey relationship and symmetric couplings in the other depicting mutualistic (or competitive) relationship, based on stability maximization through the largest eigenvalue of the corresponding adjacency matrices. We find that there is an emergence of the correlated multiplexity between the mirror nodes as the evolution progresses. Importantly, evolved values of the correlated multiplexity exhibit a dependence on the interlayer coupling strength. Additionally, the interlayer coupling strength governs the evolution of the disassortativity property in the individual layers. We provide analytical understanding to these findings by considering starlike networks representing both the layers. The framework discussed here is useful for understanding principles governing the stability as well as the importance of various patterns in the underlying networks of real-world systems ranging from the brain to ecology which consist of multiple types of interaction behavior.


Identification of a Ribose-Phosphate Pyrophosphokinase that Can Interact In Vivo with the Anaphase Promoting Complex/Cyclosome.
5-Phospho-d-ribosyl-1-diphosphate (PRPP) synthase (PRS) catalyzes the biosynthesis of PRPP, which is an important compound of metabolism in most organisms. However, no PRS genes have been cloned, let alone studied for their biological function in rubber tree. In this study, we identify a novel protein (PRS4) that interacts in vivo with rubber tree anaphase promoting complex/cyclosome (APC/C) subunit 10 (HbAPC10) by yeast two-hybrid assays. PRS4 has been cloned from rubber tree and named as HbPRS4. Blastp search in the genome of Arabidopsis thaliana showed that HbPRS4 shared the highest similarity with AtPRS4, with 80.71% identity. qRT-PCR was used to determine the expression of HbPRS4 in different tissues and under various treatments. HbPRS4 was preferentially expressed in the bark. Moreover, the expression level of HbPRS4 was significantly induced by the proteasome inhibitor MG132 treatment, suggesting it might be regulated by the ubiquitin/26S proteasome pathway. The amount of HbPRS4 transcript was obviously decreased after mechanical wounding and abscisic acid (ABA) treatments, while a slight increase was observed at 24 h after ABA treatment. HbPRS4 transcript in the latex was significantly upregulated by ethephon (ET) and methyl jasmonate (MeJA) treatments. These results suggested that HbPRS4 may be a specific substrate of HbAPC10 indirectly regulating natural rubber biosynthesis in rubber tree.


Modulation of n → π* Interaction in the Complexes of p-Substituted Pyridines with Aldehydes: A Theoretical Study.
n → π* interaction is analogous to the hydrogen bond in terms of the delocalization of the electron density between the two orbitals. Studies on the intermolecular complexes stabilized by the n → π* interaction are scarce in the literature. Herein, we have studied intermolecular N···C═O n → π* interactions in the complexes of p-substituted pyridines (p-R-Py) with formaldehyde (HCHO), formyl chloride (HCOCl), and acetaldehyde (CH3CHO) using quantum chemistry calculations. We have shown that the strength of the n → π* interaction can be modulated by varying the electronic substituents at the donor and acceptor sites in the complexes. Variation of the substituents at the para position of the pyridine ring from the electron-withdrawing groups (EWGs) to the electron-donating groups (EDGs) results in a systematic increase in the strength of the n → π* interaction. The strength of this interaction is also modulated by tuning the electron density toward the carbonyl bond by substituting the hydrogen atom of HCHO with the methyl and chloro groups. The modulation of this interaction due to the electronic substitutions at the n → π* donor and acceptor sites in the complexes is monitored by probing the relevant geometrical parameters, binding energies, C═O frequency redshift, NBO energies, and electron density for this interaction derived from QTAIM and NCI index analyses. Energy decomposition analysis reveals that the electrostatic interaction dominates the binding energies of these complexes, while the charge transfer interaction, which is representative of the n → π* interaction, also has a significant contribution to these.


Application and evaluation of a combination of socratice and learning through discussion techniques.
This article has its genesis in the inquirer's interest in the need for internalizing critical thinking, creative thinking and reflective skills in adult learners. As part of a broader study the inquirer used a combination of two techniques over a period of nine months, namely: Socratic discussion/questioning and Learning Through Discussion Technique. The inquirer within this inquiry elected mainly qualitative methods, because they were seen as more adaptable to dealing with multiple realities and more sensitive and adaptable to the many shaping influences and value patterns that may be encountered (Lincoln & Guba, 1989). Purposive sampling was used and sample size (n = 10) was determined by the willingness of potential participants to enlist in the chosen techniques. Feedback from participants was obtained: (1) verbally after each discussion session, and (2) in written format after completion of the course content. The final/summative evaluation was obtained through a semi-structured questionnaire. This was deemed necessary, in that the participants were already studying for the end of the year examination. For the purpose of this condensed report the inquirer reflected only on the feedback obtained with the help of the questionnaire. The empirical study showed that in spite of various adaptation problems experienced, eight (8) of the ten (10) participants felt positive toward the applied techniques.


Naphto-Γ-pyrones from the marine-derived fungus Aspergillus foetidus.
Nine naphto-γ-pyrones rubrofusarine B (1), TMC 256 A1 (2), fansecinones A (3) and B (4), aurasperones A (5), B (6) and F (7), dianhydro-aurasperone C (8) and asperpyrone B (9) were isolated from the marine-derived fungus Aspergillus foetidus KMM 4694. Their structures were established based on spectroscopic methods. The effect of the substances on viability and colony formation of human drug-resistant prostate cancer 22Rv1 cell was evaluated.


Influence of secondary structure on recovery from pauses during early stages of RNA transcription.
The initial stages of transcription by RNA polymerase are frequently marked by pausing and stalling events. These events have been linked to an inactive backtracked state in which the polymerase diffuses along the template DNA. We investigate theoretically the influence of RNA secondary structure in confining this diffusion. The effective confinement length peaks at transcript lengths commensurate with early stalling. This finite-size effect accounts for slow progress at the beginning of transcription, which we illustrate via stochastic hopping models for backtracking polymerases.


The graphene oxide contradictory effects against human pathogens.
Standing out as the new wonder bidimensional material, graphene oxide (GO) has aroused an exceptional interest in biomedical research by holding promise for being the antibacterial of future. First, GO possesses a specific interaction with microorganisms combined with a mild toxicity for human cells. Additionally, its antibacterial action seems to be directed to multiple targets in pathogens, causing both membranes mechanical injury and oxidative stress. Lastly, compared to other carbon materials, GO has easy and low-cost processing and is environment-friendly. This remarkable specificity and multi-targeting antibacterial activity come at a time when antibiotic resistance represents the major health challenge. Unfortunately, a comprehensive framework to understand how to effectively utilize this material against microorganisms is still lacking. In the last decade, several groups tried to define the mechanisms of interaction between GO flakes and pathogens but conflicting results have been reported. This review is focused on all the contradictions of GO antimicrobial properties in solution. Flake size, incubation protocol, time of exposure and species considered are examples of factors influencing results. These parameters will be summarized and analyzed with the aim of defining the causes of contradictions, to allow fast GO clinical application.